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1.
Transpl Immunol ; 87: 102131, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307438

RESUMEN

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

2.
Transl Neurodegener ; 13(1): 39, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095921

RESUMEN

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.


Asunto(s)
Enfermedad de Alzheimer , Endodesoxirribonucleasas , Neuronas , Proteínas tau , Animales , Proteínas tau/metabolismo , Proteínas tau/genética , Fosforilación , Ratones , Neuronas/metabolismo , Neuronas/patología , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/patología , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/deficiencia , Endodesoxirribonucleasas/metabolismo , Ratones Transgénicos , ADN/genética , Masculino , Femenino , Encéfalo/metabolismo , Encéfalo/patología , Ratones Endogámicos C57BL
3.
Mikrochim Acta ; 191(9): 567, 2024 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196429

RESUMEN

A novel photoelectrochemical (PEC) sensor for the detection of microcystic toxins (MC-LR) was developed on the basis of signal-sensitive change strategy. NiO nanoarray as a basic photoactive material was grown directly on the ITO glass electrode via calcination after hydrothermal reaction, while dye N719 was used to sensitize the electrode for enhancing visible light absorption, and the first signal-on stage was obtained. In the meantime, p-type Cu2O was applied as the signal probe attached to probe DNA (DNA2) to improve the sensitivity, and the second "signal-on" stage appeared because of its synergistic effect with NiO nanoarrays. The PEC signal decreases after the target analyte MC-LR is modified on the electrode due to the stronger affinity between MC-LR and its complementary aptamer DNA; part of the Cu2O-DNA2 will dissociate from the electrode. This sensitive signal change strategy allows the detection limit of the MC-LR sensor to be as low as 1.7 pM, which offers an optional method for the sensitive and selective detection of other target molecules, with potential applications in environmental monitoring and toxin determination.


Asunto(s)
Cobre , Técnicas Electroquímicas , Electrodos , Límite de Detección , Microcistinas , Níquel , Níquel/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Cobre/química , Microcistinas/análisis , Toxinas Marinas/análisis , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Colorantes/química , Procesos Fotoquímicos
4.
Plant Physiol Biochem ; 215: 109020, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128405

RESUMEN

Clubroot, a devastating soil borne disease affecting 30%∼50% of Brassicaceae crops worldwide, lacks effective control measures. In the present study, we explored the potential of melatonin (MT) and copper oxide nanoparticle (CuO-NPs) in mitigating clubroot severity in the Brassica rapa ssp. pekinensis. Following 18 h priming with MT, CuO-NPs, or both seeds were grown in controlled environment using synthetic potting mix. Inoculated with Plasmodiophora brassicae spores on 5th day, followed by a soil drench phyto-nano treatment with a week interval. Plants were assessed for various health and growth indices including disease, biometrics, photosynthesis, reactive oxygen species (ROS), antioxidant enzyme activity, hormones and genes expression at onset of secondary clubroot infection using established protocols. Statistical analysis employed ANOVA with Fisher's LSD for significance assessment (P < 0.05). Our results revealed that seed priming with both MT (50 µMol/L) and CuO-NPs (200 mg/L), followed by soil drenching significantly reduced clubroot incidence (38%) and disease index (57%), compared to control treatments. This synergistic effect was associated with enhanced plant growth (shoots: 48% and roots: 59%). Plants treated with both MT and CuO-NPs showed robust antioxidant defenses, significantly increased superoxide dismutase (SOD (25/29%)), catalase (CAT (83/55%)), and ascorbate peroxidase (APX (83/46%)) activity in both shoots/roots, respectively, compared to infected control. Notably, salicylic acid and jasmonic acid levels doubled in treated plants, while stress hormone abscisic acid (ABA) decreased by 80% in roots and 21% in shoots. Gene expression analysis corroborated these findings, showing that the combined treatment activated antioxidant defense genes (SOD, APX and CAT) by 1.9-7.2-fold and upregulated hormone signaling genes JAZ1 (7.8-fold), MYC2 (3.9-fold) and SABP2 (36-fold). Conversely, ABA biosynthesis genes (ABA1 and NCED1) were downregulated up to 7.2-fold, while plant resistance genes NPR1, PRB1 and PDF1.2 were dramatically increased by up to 6.3-fold compared to infected plants. Overall, our combined treatment approach significantly reduces clubroot severity in B. rapa via enhanced antioxidant defenses, improved ROS scavenging, coordinated hormonal regulation and increased pathogen response genes. This study offers promising strategy for developing effective control measures against clubroot in susceptible cruciferous crops.


Asunto(s)
Brassica rapa , Cobre , Melatonina , Enfermedades de las Plantas , Plasmodiophorida , Melatonina/farmacología , Brassica rapa/efectos de los fármacos , Brassica rapa/parasitología , Brassica rapa/crecimiento & desarrollo , Cobre/farmacología , Enfermedades de las Plantas/parasitología , Plasmodiophorida/fisiología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/parasitología , Raíces de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , Nanopartículas del Metal/química , Fotosíntesis/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ciclopentanos , Oxilipinas
5.
JMIR Public Health Surveill ; 10: e53879, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39114947

RESUMEN

Background: Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. Objective: This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. Methods: This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. Results: A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-µg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. Conclusions: PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.


Asunto(s)
Material Particulado , Nacimiento Prematuro , Tirotropina , Humanos , Femenino , Material Particulado/análisis , Material Particulado/efectos adversos , Nacimiento Prematuro/epidemiología , Tirotropina/sangre , Adulto , Embarazo , China/epidemiología , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto Joven
6.
Angew Chem Int Ed Engl ; 63(40): e202410509, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946458

RESUMEN

Heavy metal ions and antibiotic contamination have become a major environmental concern worldwide. The development of efficient recognition strategies of these pollutants at ultra-low concentrations in aqueous solutions as well as the elucidation of the intrinsic sensing mechanism are challenging tasks. In this work, unique luminescent Ln-MOF materials (NIIC-3-Ln) were assembled by rational ligand design. Among them, NIIC-3-Tb demonstrated highly selective luminescence quenching response toward Hg2+ and sulfadiazine (SDI) at subnanomolar concentrations in less than 7 s. In addition, a Hg2+ sensing mechanism through chelation was proposed on the basis of single-crystal X-ray diffraction analysis and Hg2+ adsorption study. The interaction mechanism of NIIC-3-Tb with SDI was revealed using a newly developed approach involving a (TD-)DFT based quantification of the charge transfer of a MOF-analyte supramolecular complex model in the ground and excited states. Effect of ultrasonic treatment on the surface morphology important for MOF sensing performance was revealed by gas adsorption experiments. The presented results indicate that NIIC-3-Ln is not only an advanced sensing material for the efficient detection of Hg2+ and SDI at ultra-low concentrations, but also opens up a new approach to study the sensing mechanism at the molecular level at ultra-low concentrations.

7.
Elife ; 132024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949655

RESUMEN

Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild-type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin-binding sequence) or by addition of heparin to wild-type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin-binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.


Asunto(s)
Quimiocina CCL5 , Quimiotaxis , Cricetulus , Heparitina Sulfato , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Animales , Heparitina Sulfato/metabolismo , Humanos , Células CHO , Ratones , Heparina/metabolismo , Heparina/farmacología , Separación de Fases
8.
Orphanet J Rare Dis ; 19(1): 267, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010129

RESUMEN

BACKGROUND: Late-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients. RESULTS: Neuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging. CONCLUSIONS: Intracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Humanos , Masculino , Femenino , Adulto , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico por imagen , Adulto Joven , Persona de Mediana Edad , Angiografía por Resonancia Magnética , Adolescente
9.
Plant Dis ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082928

RESUMEN

Clubroot, caused by Plasmodiophora brassicae, is a globally destructive soil-borne disease affecting cruciferous plants. Here, the predominant pathotypes of P. brassicae in six cities within Zhejiang Province were identified using the Williams and European Clubroot Differential (ECD) systems. A phylogenetic analysis of P. brassicae isolates infecting cruciferous crops worldwide was conducted using MEGA, and their ITS2 secondary structures were predicted through the ITS2 database. Accessions of B. rapa, B. oleracea, B. juncea, and Eruca sativa Mill. were employed to assess clubroot resistance. The results revealed that the prevalent pathotypes in Zhejiang Province were pathotype 1, ECD20/31/12 and ECD24/16/30; pathotype 3, ECD20/15/4; pathotype 8, ECD16/0/0 and ECD24/0/0; and pathotype 2, ECD16/15/15. Isolates from distinct genera of Brassicaceae formed separate branches in the evolutionary tree. Moreover, isolates of Brassica crops from Zhejiang Province exhibited homology with those from other global regions, a finding corroborated by their ITS2 secondary structure. Approximately 80% and 95% of B. rapa and B. juncea crops displayed susceptible phenotypes for pathotype 8, ECD16/0/0, whereas approximately 60% of B. oleracea crops exhibited resistance. Furthermore, three Brassica crop accessions showed significant variation in resistance to the pathogen, both among morphological and geographical origin groups. This study contributes to understanding the distribution of diverse P. brassicae pathotypes in different regions of Zhejiang Province and facilitates the identification of Brassica crops with potential disease resistance suitable for cultivation in the province.

10.
J Colloid Interface Sci ; 675: 815-824, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39002232

RESUMEN

Oxygen vacancy engineering in transition metal oxides is an effective strategy for improving catalytic performance. Herein, defect-enriched Mn2O3 catalysts were constructed by controlling the calcination temperature. The high content of oxygen vacancies and accompanying Mn4+ ions were generated in Mn2O3 catalysts calcined at low temperature, which could greatly improve the low-temperature reducibility and migration of surface oxygen species. DFT theoretical calculations further confirmed that molecular oxygen and toluene were easily adsorbed over defective α-Mn2O3 (222) facets with an energy of -0.29 and -0.48 eV, respectively, and corresponding OO bond length is stretched to 1.43 Å, resulting in the highly reactive oxygen species. Mn2O3-300 catalyst with abundant oxygen vacancies exhibited the highest specific reaction rate and lowest activation energy. Furthermore, the optimized catalyst possessed the outstanding stability, water tolerance and CO2 yield. In comparison with the fresh Mn2O3-300 catalyst, the physical structure and surface property of the used catalyst remained almost unchanged regardless of whether undergoing the stability test at consecutive catalytic runs as well as high temperature, and water resistance test. In situ DRIFTS spectra further elucidated that introducing the water vapor had little effect on the reaction intermediates, indicating the excellent durability of the defect-enriched catalyst.

11.
Cytotherapy ; 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38888526

RESUMEN

The one-year survival rate for patients experiencing a relapse of B-cell acute lymphocytic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT) is approximately 30%. Patients experiencing a relapse after allogeneic HSCT frequently encounter difficulties in obtaining autologous CAR-T products. We conducted a study involving 14 patients who received donor-derived CAR-T therapy for relapsed B-ALL following HSCT between August 2019 and May 2023 in our center. The results revealed a CR/CRi rate of 78.6% (11/14), a GVHD rate of 21.4% (3/14), and a 1-year overall survival (OS) rate of 56%. Decreased bone marrow donor cell chimerism in 9 patients recovered after CAR-T therapy. The main causes of death were disease progression and infection. Further analysis showed that GVHD (HR 7.224, 95% CI 1.42-36.82, P = 0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61-28.83, P = 0.009) are significantly associated with OS after CAR-T therapy. Based on the findings, we conclude that donor-derived CAR-T cells are effective in treating relapsed B-ALL patients following HSCT. Additionally, GVHD and poor platelet recovery impact OS, but further verification with a larger sample size is needed.

12.
Biomacromolecules ; 25(7): 4374-4383, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38825770

RESUMEN

Biomacromolecular condensates formed via phase separation establish compartments for the enrichment of specific compositions, which is also used as a biological tool to enhance molecule condensation, thereby increasing the efficiency of biological processes. Proteolysis-targeting chimeras (PROTACs) have been developed as powerful tools for targeted protein degradation in cells, offering a promising approach for therapies for different diseases. Herein, we introduce an intrinsically disordered region in the PROTAC (denoted PSETAC), which led to the formation of droplets of target proteins in the cells and increased degradation efficiency compared with PROTAC without phase separation. Further, using a nucleus targeting intrinsically disordered domain, the PSETAC was able to target and degrade nuclear-located proteins. Finally, we demonstrated intracellular delivery of PSETAC using lipid nanoparticle-encapsulated mRNA (mRNA-LNP) for the degradation of the endogenous target protein. This study established the PSETAC mRNA-LNP method as a potentially translatable, safe therapeutic strategy for the development of clinical applications based on PROTAC.


Asunto(s)
Proteolisis , ARN Mensajero , Proteolisis/efectos de los fármacos , Humanos , ARN Mensajero/genética , Nanopartículas/química , Lípidos/química , Células HeLa , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Separación de Fases , Liposomas
13.
Acta Neuropathol Commun ; 12(1): 66, 2024 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654316

RESUMEN

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.


Asunto(s)
Apoptosis , Ratones Endogámicos C57BL , Neuronas , Albúmina Sérica , Tauopatías , Animales , Humanos , Masculino , Ratones , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Astrocitos/metabolismo , Astrocitos/patología , Astrocitos/efectos de los fármacos , Elongasas de Ácidos Grasos/metabolismo , Microglía/metabolismo , Microglía/efectos de los fármacos , Microglía/patología , Neuronas/metabolismo , Neuronas/patología , Neuronas/efectos de los fármacos , Albúmina Sérica/metabolismo , Albúmina Sérica/farmacología , Proteínas tau/metabolismo , Tauopatías/patología , Tauopatías/metabolismo
14.
China CDC Wkly ; 6(12): 230-234, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38633432

RESUMEN

What is already known about this topic?: Brucellosis, mainly caused by Brucella melitensis (B. melitensis), is regarded as a significant zoonotic disease in China. In Weihai, located at the eastern end of the Shandong Peninsula, brucellosis has been in a low epidemic phase for the past five years. What is added by this report?: This was the initial report of a brucellosis outbreak in the last five years. Strains of B. melitensis bv. 3 from Weihai and other cities showed a close genetic relationship, suggesting a potential common ancestry. What are the implications for public health practice?: Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace outbreaks. Understanding the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.

15.
Heliyon ; 10(5): e26765, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38434420

RESUMEN

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility.

16.
Int Immunopharmacol ; 130: 111766, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38452411

RESUMEN

OBJECTIVES: This study aimed to investigate the effect of calcitonin gene-related peptide (CGRP) on the temporal alteration of macrophage phenotypes and macrophage-regulated angiogenesis duringearlybonehealing and preliminarily elucidate the mechanism. METHODS: In vivo, the rat mandibular defect models were established with inferior alveolar nerve transection (IANT) or CGRP receptor antagonist injection. Radiographicandhistologic assessments for osteogenesis, angiogenesis, and macrophage phenotypic alteration within bone defects were performed. In vitro, the effect and mechanism of CGRP on macrophage polarization and phenotypic alteration were analyzed. Then the conditioned medium (CM) from CGRP-treated M1 or M2 macrophages was used to culture human umbilical vein endothelial cells (HUVECs), and the CGRP's effect on macrophage-regulated angiogenesis was detected. RESULTS: Comparable changes following IANT and CGRP blockade within bone defects were observed, including the suppression of early osteogenesis and angiogenesis, the prolonged M1 macrophage infiltration and the prohibited transition toward M2 macrophages around vascular endothelium. In vitro experiments showed that CGRP promoted M2 macrophage polarization while upregulating the expression of interleukin 6 (IL-6), a major cytokine that facilitates the transition from M1 to M2-dominant stage, in M1 macrophages via the activation of Yes-associated protein 1. Moreover, CGRP-treated macrophage-CM showed an anabolic effect on HUVECs angiogenesis compared with macrophage-CM and might prevail over the direct effect of CGRP on HUVECs. CONCLUSIONS: Collectively, our results reveal the effect of CGRP on M1 to M2 macrophage phenotypic alteration possibly via upregulating IL-6 in M1 macrophages, and demonstrate the macrophage-regulated pro-angiogenic potential of CGRP in early bone healing.


Asunto(s)
Regeneración Ósea , Huesos , Péptido Relacionado con Gen de Calcitonina , Interleucina-6 , Macrófagos , Neovascularización Fisiológica , Animales , Humanos , Ratas , Péptido Relacionado con Gen de Calcitonina/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Interleucina-6/metabolismo , Macrófagos/citología , Macrófagos/fisiología , Fenotipo , Ratas Sprague-Dawley , Femenino , Huesos/irrigación sanguínea
17.
J Orthop Surg Res ; 19(1): 112, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38308336

RESUMEN

PURPOSE: This research aimed to develop a machine learning model to predict the potential risk of prolonged length of stay in hospital before operation, which can be used to strengthen patient management. METHODS: Patients who underwent posterior spinal deformity surgery (PSDS) from eleven medical institutions in China between 2015 and 2022 were included. Detailed preoperative patient data, including demographics, medical history, comorbidities, preoperative laboratory results, and surgery details, were collected from their electronic medical records. The cohort was randomly divided into a training dataset and a validation dataset with a ratio of 70:30. Based on Boruta algorithm, nine different machine learning algorithms and a stack ensemble model were trained after hyperparameters tuning visualization and evaluated on the area under the receiver operating characteristic curve (AUROC), precision-recall curve, calibration, and decision curve analysis. Visualization of Shapley Additive exPlanations method finally contributed to explaining model prediction. RESULTS: Of the 162 included patients, the K Nearest Neighbors algorithm performed the best in the validation group compared with other machine learning models (yielding an AUROC of 0.8191 and PRAUC of 0.6175). The top five contributing variables were the preoperative hemoglobin, height, body mass index, age, and preoperative white blood cells. A web-based calculator was further developed to improve the predictive model's clinical operability. CONCLUSIONS: Our study established and validated a clinical predictive model for prolonged postoperative hospitalization duration in patients who underwent PSDS, which offered valuable prognostic information for preoperative planning and postoperative care for clinicians. Trial registration ClinicalTrials.gov identifier NCT05867732, retrospectively registered May 22, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05867732 .


Asunto(s)
Algoritmos , Hospitales , Humanos , Estudios de Cohortes , Tiempo de Internación , Aprendizaje Automático
18.
Food Chem ; 445: 138747, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387317

RESUMEN

A new 3D metal-organic framework {[Cd16(tr2btd)10(dcdps)16(H2O)3(EtOH)]∙15DMF}n (MOF 1, tr2btd = 4,7-di(1,2,4-triazol-1-yl)benzo-2,1,3-thiadiazole, H2dcdps = 4,4'-sulfonyldibenzoic acid) was obtained and its luminescent properties were studied. MOF 1 exhibited bright blue-green luminescence with a high quantum yield of 74 % and luminescence quenching response to a toxic natural polyphenol gossypol and luminescence enhancement response to some trivalent metal cations (Fe3+, Cr3+, Al3+ and Ga3+). The limit of gossypol detection was 0.20 µM and the determination was not interfered by the components of the cottonseed oil. The limit of detection of gallium(III) was 1.1 µM. It was demonstrated that MOF 1 may be used for distinguishing between the genuine sunflower oil and oil adulterated by crude cottonseed oil through qualitative luminescent and quantitative visual gossypol determination.


Asunto(s)
Galio , Gosipol , Estructuras Metalorgánicas , Petróleo , Aceite de Semillas de Algodón , Luminiscencia , Culinaria
19.
Adv Mater ; 36(19): e2311939, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38275004

RESUMEN

Highly selective and sensitive quantitative detection of ofloxacin (OFX) at ultralow concentrations in aqueous media and development of new afterglow materials remains a challenge. Herein, a new 2D water-stable lanthanide metal-organic framework (NIIC-2-Tb) is proposed, which exhibits high selectivity towards OFX through the luminescence quenching with the lowest detection limit (1.1 × 10-9 M) reported to date and a fast response within 6 s. In addition, the luminescent detection of OFX by NIIC-2-Tb is not affected by typical components of blood plasma and urine. The excellent sensing effect of NIIC-2-Tb is further utilized to prepare a composite functional sensing carrageenan hydrogel material for the rapid detection of OFX in meat in real time and the first discovery of impressive afterglow in MOF-based hydrogels. This study not only presents novel Ln-MOF materials and Ln-MOF-based hydrogel films for luminescent sensing of OFX, but also demonstrates color-tunable luminescent films with afterglow, which expands the application of composite luminescent materials for detection and anti-counterfeiting.


Asunto(s)
Hidrogeles , Estructuras Metalorgánicas , Ofloxacino , Ofloxacino/orina , Ofloxacino/análisis , Ofloxacino/sangre , Ofloxacino/química , Estructuras Metalorgánicas/química , Hidrogeles/química , Luminiscencia , Límite de Detección , Mediciones Luminiscentes/métodos , Terbio/química , Carragenina/química , Metilgalactósidos
20.
ACS Appl Mater Interfaces ; 16(4): 5129-5137, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38227932

RESUMEN

Adenosine triphosphate (ATP) is a small molecule that is released to the urine from bladder urothelial cells and the bladder mucosal band of the human body. In certain cases, ATP can serve as a biomarker in bladder disease. For the practical applicability of luminescent sensors for ATP in urine, it is significant to find a new strategy for making the detection progress simple and available for in-field urine analysis. Here, a novel luminescent lanthanide coordination polymer (Tb-BPA) was designed and synthesized for quick and sensitive detection of ATP through luminescence quenching with a quenching constant of 4.90 × 103 M-1 and a detection limit of 0.55 × 10-6 M. Besides, Tb-BPA has excellent anti-interference ability and can detect ATP in simulated urine with a small relative standard deviation (<4%). Moreover, the luminescent polyacrylonitrile nanofiber films modified by Tb-BPA were prepared by electrospinning and were used for ATP visual detection. Notably, this film is easy to recover and reuse, and maintains good detection performance after at least 7 cycles.


Asunto(s)
Elementos de la Serie de los Lantanoides , Humanos , Adenosina Trifosfato/análisis , Polímeros , Luminiscencia
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