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Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.
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Histonas , Ácido Láctico , Microglía , Recuperación de la Función , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Histonas/metabolismo , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Ácido Láctico/metabolismo , Ratas , Lisina/metabolismo , Lisina/análogos & derivados , Lisina/farmacología , Ratones , Cicatriz/metabolismo , Cicatriz/patología , Femenino , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Masculino , Locomoción/efectos de los fármacos , Locomoción/fisiologíaRESUMEN
Accurate body temperature measurement is essential for monitoring and managing safety during outdoor activities. Physical activities are an essential consideration for public health, with sports taking up an important proportion of these. Athletes' performances can be directly affected by body temperature fluctuations, with overheating or hypothermia posing serious health risks. Monitoring these temperatures allows coaches and medical staff to make decisions that enhance performance and safety. Traditional methods, like oral, axillary, and tympanic readings, are widely used, but face challenges during intense physical activities in real-world environments. This study evaluated the agreement, correlation, and interchangeability of oral, axillary, and tympanic temperature measurements in outdoor exercise conditions. Systems developed for specific placements might generate different sensor readouts. Conducted as an observational field study, it involved 21 adult participants (11 males and 10 females, average age 25.14 ± 5.80 years) that underwent the Yo-Yo intermittent recovery test protocol on an outdoor court. The main outcomes measured were the agreement and correlation between temperature readings from the three methods, both before and after exercise. The results indicate poor agreement between the measurement sites, with significant deviations observed post-exercise. Although the Spearman correlation coefficients showed consistent temperature changes post-exercise across all methods, the standard deviations in the pairwise comparisons exceeded 0.67 °C. This study concluded that widely used temperature measurement methods are challenging to use during outdoor exercises and should not be considered interchangeable. This variability, especially after exercise, underscores the need for further research using gold standard temperature measurement methods to determine the most suitable site for accurate readings. Care should thus be taken when temperature screening is done at scale using traditional methods, as each measurement site should be considered within its own right.
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Temperatura Corporal , Ejercicio Físico , Humanos , Masculino , Adulto , Femenino , Adulto Joven , Boca/fisiología , Oído/fisiología , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentaciónRESUMEN
BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.
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Proteínas de Microfilamentos , Microglía , Traumatismos de la Médula Espinal , Animales , Ratones , Proteínas Portadoras , Gliosis/metabolismo , Proteínas de Microfilamentos/metabolismo , Microglía/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/patologíaRESUMEN
In recent years, non-contact infrared thermometers (NCITs) and infrared thermography (IRT) have gained prominence as convenient, non-invasive tools for human body temperature measurement. Despite their widespread adoption in a range of settings, there remain questions about their accuracy under varying conditions. This systematic review sought to critically evaluate the performance of NCITs and IRT in body temperature monitoring, synthesizing evidence from a total of 72 unique settings from 32 studies. The studies incorporated in our review ranged from climate-controlled room investigations to clinical applications. Our primary findings showed that NCITs and IRT can provide accurate and reliable body temperature measurements in specific settings and conditions. We revealed that while both NCITs and IRT displayed a consistent positive correlation with conventional, contact-based temperature measurement tools, NCITs demonstrated slightly superior accuracy over IRT. A total of 29 of 50 settings from NCIT studies and 4 of 22 settings from IRT studies achieved accuracy levels within a range of ±0.3 °C. Furthermore, we found that several factors influenced the performance of these devices. These included the measurement location, the type of sensor, the reference and tool, individual physiological attributes, and the surrounding environmental conditions. Our research underscores the critical need for further studies in this area to refine our understanding of these influential factors and to develop standardized guidelines for the use of NCITs and IRT.
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Temperatura Corporal , Termómetros , Humanos , Clima , Primeros AuxiliosRESUMEN
BACKGROUND: Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such as tumour size and catecholamine levels are reported to predict haemodynamic responses during surgery for PPGL. We hypothesized that additional factors including body composition and genetic information could further improve prediction. METHODS: Consecutive patients with PPGL confirmed by surgical pathology between June 2010 and June 2019 were retrospectively included. Cross-sectional computed tomography images at the L3 level were used to assess body composition parameters including skeletal muscle area and visceral fat area. Next-generation sequencing was performed using a panel containing susceptibility genes of PPGL. Differences in clinical-genetic characteristics and body composition parameters were analysed and compared in patients with and without intraoperative haemodynamic instability (HDI). RESULTS: We included 221 patients with PPGL (median age 47 [38-56] years, and 52% male). Among them, 49.8% had Cluster 2 mutations (related to kinase signalling pathways), 44.8% had sarcopenia, and 52.9% experienced intraoperative HDI. Compared with patients without HDI, more patients with HDI had Cluster 2 mutations (59.8% vs. 38.5%, P = 0.002) and less had sarcopenia (35.9% vs. 54.8%, P = 0.005). Multivariate analysis showed that urine vanillylmandelic acid ≥ 58 µmol/day (adjusted odds ratio [OR] = 1.840, 95% confidence interval [CI] = 1.012-3.347, P = 0.046), tumour size ≥ 4 cm (adjusted OR = 2.278, 95% CI = 1.242-4.180, P = 0.008), and Cluster 2 mutations (adjusted OR = 2.199, 95% CI = 1.128-4.285, P = 0.021) were independent risk factors for intraoperative HDI, while sarcopenia (adjusted OR = 0.475, 95% CI = 0.266-0.846, P = 0.012) decreased the risk. CONCLUSIONS: Body composition and genotype were associated with intraoperative haemodynamics in patients with PPGL. Our results indicated that inclusion of body composition and genotype in the overall assessment of patients with PPGL helped to predict HDI during surgery, which could assist in implementing preoperative and intraoperative measures to reduce perioperative complications.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Estudios Transversales , Feocromocitoma/genética , Feocromocitoma/cirugía , Feocromocitoma/complicaciones , Paraganglioma/genética , Paraganglioma/cirugía , Paraganglioma/complicaciones , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/patología , Composición CorporalRESUMEN
OBJECTIVE: Early detection of platinum resistance for ovarian cancer treatment remains challenging. This study aims to develop a machine learning model incorporating genomic data such as Single-Nucleotide Polymorphisms (SNPs) of Human Sulfatase 1 (SULF1) with a CT radiomic model based on pre-treatment CT images, to predict platinum resistance for ovarian cancer (OC) treatment. METHODS: A cohort of 102 patients with pathologically confirmed OC was retrospectively enrolled into this study from January 2006 to February 2018. All patients had platinum-based chemotherapy after maximal cyto-reductive surgery. This cohort was separated into two groups according to treatment response, i.e., the group with platinum-resistant disease (PR group) and the group with platinum-sensitive disease (PS group). We genotyped 12 SNPs of SULF1 for all OC patients using Mass Array Method. Radiomic features, SNP data and clinicopathological data of the 102 patients were used to build the differentiation models. The study participants were divided into two cohorts: the training cohort (n = 71) and the validation cohort (n = 31). Feature selection and predictive modeling were performed using least absolute shrinkage and selection operator (LASSO), Random Forest Classifier and Support Vector Machine methods. Model performance for predicting platinum resistance was assessed with respect to its calibration, discrimination, and clinical application. RESULTS: For prediction of platinum resistance, the approach combining the radiomics, clinicopathological data and SNP data demonstrated higher classification efficiency, with an AUC value of 0.993 (95 % CI: 0.83 to 0.98) in the training cohort and 0.967 (95 % CI: 0.83 to 0.98) in validation cohort, than the performance with only the SNPs of SULF1 model (AUC: training, 0.843 [95 %CI: 0.738-0.948]; validation, 0.815 [0.601-1.000]), or with only the radiomic model (AUC: training, 0.874 [95 %CI: 0.789-0.960]; validation, 0.832 [95 %CI: 0.687-0.976]). This integrated approach also showed good calibration and favorable clinical utility. CONCLUSIONS: A predictive model combining pretreatment CT radiomics with genomic data such as SNPs of SULF1 could potentially help to predict platinum resistance in ovarian cancer treatment.
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Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/genética , Tomografía Computarizada Multidetector , Neoplasias Ováricas/tratamiento farmacológico , Pruebas de Farmacogenómica , Variantes Farmacogenómicas , Compuestos de Platino/uso terapéutico , Polimorfismo de Nucleótido Simple , Genómica de la Radiación , Sulfotransferasas/genética , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Aprendizaje Automático , Persona de Mediana Edad , Variaciones Dependientes del Observador , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/genética , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
When low-concentration rural sewage is treated biologically, the effluent total nitrogen (TN) concentration often does not meet the discharge limit because of its low carbon-to-nitrogen ratio (C/N). To solve this problem, a laboratory-scale anoxic/oxic (A/O) biofilter packed with Arundo donax and activated carbon as the anoxic and aerobic column fillers (No. 2) was operated for treatment of simulated rural sewage and advanced nitrogen removal, while an ordinary gravel-packing A/O biofilter (No. 1) was set up as the control group. The results were as follows. When the influent chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and TN concentrations were (79.47±14.21), (34.49±2.08), and (34.73±3.87) mg·L-1, respectively, the No. 1 and No. 2 reactors achieved removal efficiencies of (88.00±7.00)% and (89.00±10.00)%, (90.00±2.00)% and (97.00±7.00)%, and (37±15)% and (68±7)%, respectively. The results revealed that using Arundo donax and activated carbon new fillers could significantly enhance NH4+-N and TN removal. High-throughput sequencing results indicated that the microorganisms involved in the nitrification process in the No. 1 reactor mainly belong to Proteobacteria, whereas those in the No. 2 reactor belong to Proteobacteria and Nitrospirae. In addition, the main denitrification bacterial phyla in the anoxic column of the No. 1 reactor were Chloroflexi, Proteobacteria, Bacteroidetes, and Planctomycetes, whereas those in the anoxic column of the No. 2 reactor were primarily Bacteroidetes, Proteobacteria, Firmicutes, and Patescibacteria. Quantitative real time polymerase chain reaction (qPCR) results showed that the microbial nitrification (amoA and Nitrospira 16S rDNA), denitrification (narG, nosZ, nirS, and nirK), and anaerobic ammonium oxidation functional genes (ANAMMOX) in the No. 2 reactor were significantly higher than those in the No. 1 reactor. All the genes, except for the narG and nosZ genes, had one to two orders of magnitude of improvement in the No. 2 reactor compared to those in the No. 1 reactor.
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In order to study the generation and extraction of negative ions for neutral beam injection application, a prototype radio frequency driven negative ion source and the corresponding test bench are under construction at the Institute of Plasma Physics, Chinese Academy of Sciences. A new design of infrared radiation diagnostic calorimeter for testing beam characteristics is put forward. Compared with the conventional calorimeter, the calorimeter adopts the block structure (8 × 28 tungsten hexahedron blocks) and modularization design (4 modules), so it has higher precision and good scalability. The thermal performance of the calorimeter is assessed using a finite element method. Simulation results show that the design can be achieved to operate in the stable-state mode at the maximum thermal flux 6.45 MW/m2 and meet the full requirement of beam diagnosis.
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This study assesses the spatial distribution characteristics and ecological risk of phthalate esters (PAEs) in the surface sediments of the mainstream and tributaries of the Songhua River, China, using concentrations and composition of six PAEs, which were analyzed using gas chromatography-mass spectrometery (GC-MS). We assess the ∑6PAEs ecological risk using the hazard quotient (HQ) method and environmental risk levels (ERL). The results were as follows. â It was found that the total concentrations of ∑6PAEs ranged from 6832.5 to 36298.9 ng·g-1 dry weight (average 18388.6 ng·g-1), with the main contributions coming from di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP). The difference between the main stream ∑6PAEs (6832.5-36298.9 ng·g-1, average 18616.9 ng·g-1) and the tributary ∑6PAEs (10367.6-26593.3 ng·g-1, average 18264.1 ng·g-1) was not significant (P >0.05). The mean concentrations of individual PAEs in the tributary stream differed little from that of the main stream. The ∑6PAEs concentration of the Songhua River decreased initially but then increased from the upstream to the downstream. The average ∑6PAEs concentration in natural agricultural areas (18677.5 ng·g-1) was similar to that found in urban industrial areas (18063.7 ng·g-1), and DBP and DEHP contributed 98% of ∑6PAEs. â¡ The main sources of ∑6PAEs were domestic, agricultural production, and industrial production using plasticizers. ⢠The ecological risk assessment indicated that DMP and BBP in the surface sediments of the Songhua River did not pose an ecological risk for aquatic organisms, and that DEP was associated with a low ecological risk, whereas DEHP and DBP posed a high ecological risk for aquatic organisms.
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Ésteres/análisis , Sedimentos Geológicos/química , Ácidos Ftálicos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , China , Dibutil Ftalato , Medición de RiesgoRESUMEN
Neutral beam injection (NBI) is one of the most effective tools of four auxiliary plasma heating methods for fusion plasma heating and current drive. Now, a next generation fusion device, China Fusion Engineering Test Reactor, is under design, and a large negative NBI is foreseen. In order to demonstrate the key technology and performance of a negative ion source, a negative radio frequency (RF) ion source test facility has been developed since 2017 in the Institute of Plasma Physics, Chinese Academy of Science. A prototype RF ion source with double drivers (having the same structure with an inner diameter of 200 mm) was developed and tested on the test facility to preresearch the key technology of the RF plasma generator. The driver is equipped with a water-cooled Faraday shield to protect the alumina cylinder from the plasma, and the plasma expands into the rectangular expansion chamber. The RF power of 100 kW with a frequency of 1 MHz is transferred to the RF driver by a matching unit. The characteristics of plasma discharge were studied with classical diagnostic tools, such as the Langmuir probe and water flow calorimeter. Based on the plasma performance tests, a high power of 82 kW plasma discharge for a long pulse of 1000 s was achieved. In this paper, the details of the ion source design, characteristics of plasma, and future research plan will be presented.
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The filling ratio (FR) of a carrier has an influence on the pollutant removal of the aerobic moving bed biofilm reactor (MBBR). However, the effect of the polyethylene (PE) carrier FR on the performance and microbial characteristics of the denitrifying MBBR for the treatment of wastewater treatment plant (WWTP) effluent has not been extensively studied. A bench-scale denitrifying MBBR was set up and operated with PE carrier FRs of 20%, 30%, 40%, and 50% for the degradation of chemical oxygen demand (COD) and nitrogen from WWTP effluent at 12 h hydraulic retention time (HRT). The nitrate removal rates with FRs of 20%, 30%, 40%, and 50% were 94.3 ± 3.9%, 87.7 ± 7.3%, 89.7 ± 11.6%, and 94.6 ± 4.0%, and the corresponding denitrification rates (rNO3--N) were 8.0 ± 5.6, 11.3 ± 4.6, 11.6 ± 4.6, and 10.0 ± 4.9 mg NO3--N/L/d, respectively. Nitrous oxide reductase (nosZ) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis illustrated that the highest functional diversity (Shannon's diversity index, H') of biofilm microbial community was obtained at 30% FR. The quantitative polymerase chain reaction (qPCR) results indicated that the abundance of nitrate reductase (narG) and nosZ genes at 30% FR was significantly higher than that at 20% FR, and no significant changes were observed at 40% and 50% FRs. Thus, 30% FR was recommended as the optimal carrier FR for the denitrifying MBBR.
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Reactores Biológicos , Desnitrificación , Eliminación de Residuos Líquidos/métodos , Biopelículas , Análisis de la Demanda Biológica de Oxígeno , Nitrógeno/análisis , Polietileno , Aguas Residuales/análisis , Contaminantes del Agua/análisisRESUMEN
Negative ion source is a core part of the neutral beam injection system for magnetic confinement fusion devices. The density of produced hydrogen negative ions is a critical parameter of the negative ion source. Cavity ring-down spectroscopy (CRDS) is an ultrasensitive absorption diagnostic technique for density measurement. Based on the photodetachment process, CRDS can measure the integrated line-of-sight hydrogen negative ion density in a high power ion source. The CRDS diagnostic system has been applied to Hefei utility negative ion test equipment with the radio frequency (RF) source, which is now one of the references for the China Fusion Engineering Test Reactor neutral beam injection system. Typical ring-down signals are obtained to calculate the density of hydrogen negative ions. The time evolution of hydrogen negative ion density is successfully measured. Preliminary experiments show the accurate relationship between RF power and measured hydrogen negative ion density.