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High-strength bolts play a crucial role in ultra-high-pressure equipment such as bridges and railway tracks. Effective monitoring of bolt conditions is of paramount importance for common fault repair and accident prevention. This paper aims to detect and classify bolt corrosion levels accurately. We design and implement a bolt corrosion classification system based on a Wireless Acoustic Emission Sensor Network (WASN). Initially, WASN nodes collect high-speed acoustic emission (AE) signals from bolts. Then, the ReliefF feature selection algorithm is applied to identify the optimal feature combination. Subsequently, the Extreme Learning Machine (ELM) model is utilized for bolt corrosion classification. Additionally, to achieve high prediction accuracy, an improved goose algorithm (GOOSE) is employed to ensure the most suitable parameter combination for the ELM model. Experimental measurements were conducted on five classes of bolt corrosion levels: 0%, 25%, 50%, 75%, and 100%. The classification accuracy obtained using the proposed method was at least 98.04%. Compared to state-of-the-art classification diagnostic models, our approach exhibits superior AE signal recognition performance and stronger generalization ability to adapt to variations in working conditions.
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CONTEXT: Pain and symptoms of patellofemoral pain (PFP) are often exacerbated during daily activities, which may result in reduced overall physical activity levels. OBJECTIVE: To summarize the evidence for physical activity levels among persons with PFP compared with pain-free controls. DATA SOURCES: PubMed, Embase, CINHAL, Cochrane Library, and SPORTDiscus were searched from January 1, 2000 to February 22, 2024. STUDY SELECTION: Peer-reviewed studies published in English that measured physical activity subjectively or objectively in persons with PFP and pain-free controls. STUDY DESIGN: Systematic review with meta-analysis. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Standardized mean difference (SMD) with 95% CI are reported based on Hedges' g effect sizes. RESULTS: From 23,745 records, 41 studies met the eligibility criteria. There was high-to-moderate-certainty evidence that persons with PFP reported higher physical activity levels compared with pain-free controls using the International Physical Activity Questionnaire (SMD, 0.27; 95% CI 0.03, 0.51), whereas lower physical activity levels compared with pain-free controls using the Tegner Activity Scale (SMD, -0.31; 95% CI -0.57, -0.04). There was low-to-moderate-certainty evidence that there was no group difference in physical activity levels using the Baecke Physical Activity Questionnaire (SMD, 0.17; 95% CI -0.09, 0.44) or self-reported sports participation duration (SMD, -0.46; 95% CI -0.98, 0.05). There was high-certainty evidence that runners with PFP reported shorter running distances compared with pain-free runners (SMD, -0.36, 95% CI -0.57, -0.14). No data pooling was possible for objectively measured physical activity levels due to device heterogeneity (ie, different algorithms used to quantify the intensity of physical activity). CONCLUSION: Self-reported physical activity levels among persons with PFP were inconsistent depending on the physical activity measurement tool used or which specific physical activity was measured. Clinicians should integrate multiple physical activity assessment tools to determine the extent to which PFP influences physical activity levels. TRIAL REGISTRATION: PROSPERO #CRD42022314598.
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Centrosome amplification (CA), an abnormal increase in the number of centrosomes in the cell, is a recurrent phenomenon in lung and other malignancies. Although CA promotes tumor development and progression by inducing genomic instability (GIN), it also induces mitotic stress that jeopardizes cellular integrity. CA leads to the formation of multipolar mitotic spindles that can cause lethal chromosome segregation errors. To sustain the benefits of CA by mitigating its consequences, malignant cells are dependent on adaptive mechanisms that represent therapeutic vulnerabilities. We aimed to discover genetic dependencies associated with CA in lung cancer. Combining a CRISPR/Cas9 functional genomics screen with tumor genomic analyses, we identified the motor protein KIFC1, also known as HSET, as a putative vulnerability specifically in lung adenocarcinoma (LUAD) with CA. KIFC1 expression was positively correlated with CA in LUAD and associated with worse patient outcomes, smoking history, and indicators of GIN. KIFC1 loss-of-function sensitized LUAD cells with high basal KIFC1 expression to potentiation of CA, which was associated with a diminished ability to cluster extra centrosomes into pseudo-bipolar mitotic spindles. Our work suggests that KIFC1 inhibition represents a novel approach for potentiating GIN to lethal levels in LUAD with CA by forcing cells to divide with multipolar spindles, rationalizing further studies to investigate its therapeutic potential.
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Lysosomal degradation pathways coordinate the clearance of superfluous and damaged cellular components. Compromised lysosomal degradation is a hallmark of many degenerative diseases, including lysosomal storage diseases (LSDs), which are caused by loss-of-function mutations within both alleles of a lysosomal hydrolase, leading to lysosomal substrate accumulation. Gaucher's disease, characterized by <15% of normal glucocerebrosidase function, is the most common LSD and is a prominent risk factor for developing Parkinson's disease. Here, we show that either of two structurally distinct small molecules that modulate PIKfyve activity, identified in a high-throughput cellular lipid droplet clearance screen, can improve glucocerebrosidase function in Gaucher patient-derived fibroblasts through an MiT/TFE transcription factor that promotes lysosomal gene translation. An integrated stress response (ISR) antagonist used in combination with a PIKfyve modulator further improves cellular glucocerebrosidase activity, likely because ISR signaling appears to also be slightly activated by treatment by either small molecule at the higher doses employed. This strategy of combining a PIKfyve modulator with an ISR inhibitor improves mutant lysosomal hydrolase function in cellular models of additional LSD.
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Fibroblastos , Glucosilceramidasa , Enfermedades por Almacenamiento Lisosomal , Lisosomas , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Glucosilceramidasa/metabolismo , Glucosilceramidasa/genética , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Enfermedades por Almacenamiento Lisosomal/tratamiento farmacológico , Enfermedades por Almacenamiento Lisosomal/genética , Enfermedades por Almacenamiento Lisosomal/metabolismo , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Enfermedad de Gaucher/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacologíaRESUMEN
BACKGROUND: Botulinum toxin (BTX) is an effective management method for spasticity in children with cerebral palsy (CP), but the short- medium- and long-term effects remain unclear. OBJECTIVE: The primary objective was to quantify the effects of BTX injections on upper limb spasticity over time in children with CP. The secondary objective was to evaluate efficacy according to the International Classification of Functioning, Disability, and Health-Children & Youth version framework. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that included control/comparison groups treated with a placebo or other treatments. We searched CINAHL, Embase, PubMed, Scopus, Web of Science, and PsycINFO from their inception to April 2024. The pooled mean difference (MD) or standard mean difference (SMD) with 95 % CI was calculated using a random effects model at the short-term (up to 3 months), medium-term (3 to 6 months), and long-term (over 6 months). RESULTS: A total of 658 children with CP aged 1.8 to 19 years old in 12 eligible trials were involved. The primary outcome of the Melbourne Assessment percentile showed a significant increase in the medium- (MD = 2.63, 95 % CI 0.22 to 5.04, I² = 0 %) and long-term (MD = 4.72, 95 % CI 0.93 to 8.51, I² = 0 %) in favor of BTX. Pooled effects also showed that BTX significantly improved Modified Ashworth Scale scores in the short- (MD = -0.44, 95 % CI -0.88 to -0.01, I² = 88 %) and medium-term (MD = -0.20, 95 % CI -0.28 to -0.13, I² = 0 %), and individual goals and bimanual performance up to 6-months. No significantly higher risk of adverse events was observed with BTX. CONCLUSIONS AND IMPLICATIONS: BTX injections sustainably improved the quality of affected upper limb function and temporarily improved individual goals and bimanual performance in children with CP. Our findings cautiously support a time interval of 3 to 6 months between BTX injections in the upper limbs of children with CP. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD42022323672).
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Background: Osteoporosis remains substantially underdiagnosed and undertreated worldwide. Chest low-dose computed tomography (LDCT) may provide a valuable and popular opportunity for osteoporosis screening. This study sought to evaluate the feasibility of the screening of low bone mineral density (BMD) and osteoporosis with mean attenuation values of the lower thoracic compared to upper lumbar vertebrae. The cutoff thresholds of the mean attenuation values in Hounsfield units (HU) were derived to facilitate implementation of opportunistic screening using chest LDCT. Methods: The participants aged 30 years or older who underwent chest LDCT and quantitative computed tomography (QCT) examinations from August 2018 to October 2020 in our hospital were consecutively included in this retrospective study. A region of interest (ROI) was placed in the trabecular bone of each vertebral body to measure the HU values. The correlations of mean HU values of lower thoracic (T11-T12) and upper lumbar (L1-L2) vertebrae with age and lumbar BMD obtained with QCT were performed using the Pearson correlation coefficient, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was generated to determine the cutoff thresholds for distinguishing low BMD from normal and osteoporosis from non-osteoporosis. Results: A total of 1,112 participants were included in the final study cohort (743 men and 369 women, mean age 58.2±8.9 years; range, 32-88 years). The mean HU values of T11-T12 and L1-L2 were significantly different among 3 QCT-defined BMD categories of osteoporosis, osteopenia, and normal (P<0.001). The differences in HU values between T11-T12 and L1-L2 in each category of bone status were statistically significant (P<0.001). The mean HU values of T11-T12 (r=-0.453, P<0.001) and L1-L2 (r=-0.498, P<0.001) had negative correlations with age. Positive correlations were observed between the mean HU values of T11-T12 (r=0.872, P<0.001) and L1-L2 (r=0.899, P<0.001) with BMD. The optimal cutoff thresholds for distinguishing low BMD from normal were average T11-T12 ≤157 HU [AUC =0.941, 95% confidence interval (CI): 0.925-0.954, P<0.001] and L1-L2 ≤138 HU (AUC =0.950, 95% CI: 0.935-0.962, P<0.001), as well as distinguishing osteoporosis from non-osteoporosis were average T11-T12 ≤125 HU (AUC =0.960, 95% CI: 0.947-0.971, P<0.001) and L1-L2 ≤107 HU (AUC =0.961, 95% CI: 0.948-0.972, P<0.001). There was no significant difference between the AUC values of T11-T12 and L1-L2 for low BMD (P=0.07) and osteoporosis (P=0.92) screening. Conclusions: We have conducted a study on low BMD and osteoporosis screening using mean attenuation values of lower thoracic and upper lumbar vertebrae. Assessment of mean attenuation values of T11-T12 and L1-L2 can be used interchangeably for low BMD and osteoporosis screening using chest LDCT, and their cutoff thresholds were established.
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BACKGROUND: Firefighters have a high prevalence of cardiovascular disease. The poor heart health of firefighters is implicated in their increased risk of sudden cardiac death (SCD). Exercise may be protective against SCD partially due to the immediate blood pressure (BP) reductions of 5-8 mmHg following exercise, termed postexercise hypotension (PEH) OBJECTIVES: To examine PEH under ambulatory conditions after a maximal cardiopulmonary exercise test (CPET) among career firefighters METHODS: Firefighters (n = 19) completed a maximal CPET and non-exercise control (CONTROL) in random order on separate non-workdays and left the laboratory instrumented to an ambulatory BP (ABP) monitor. Ambulatory systolic BP (ASBP), diastolic BP (ADBP), and heart rate (AHR) were recorded at hourly intervals over 19hr. The ambulatory rate pressure product (ARPP) was calculated as ASBPxAHRx10-3 at each hourly interval. Repeated measures ANCOVA tested if the ABP, AHR, and ARPP responses differed after CPET vs CONTROL over 19hr RESULTS: Firefighters were middle-aged (39.5 ± 8.9 yr), overweight (29.2 ± 4.0 kg/m2) men with elevated BP (123.1 ± 9.6/79.8 ± 10.4 mmHg), while resting HR (67.7 ± 11.3 bpm) and RPP (8.4 ± 1.7mmHg*bpm*10-3) were in normal ranges. ASBP (16.6 ± 5.7 mmHg) and ADBP (3.1 ± 4.6 mmHg) increased after the CPET vs CONTROL over 19hr (ps<0.01), as did AHR (9.4 ± 7.9 bpm, p = 0.02) and ARPP (2.5 ± 1.1mmHg*bpm*10-3, p < 0.01). CONCLUSIONS: Unexpectedly, the firefighters exhibited postexercise hypertension rather than PEH. The increases in ABP and AHR we observed indicated a sustained increase in cardiac demand. Further investigation is needed to confirm our findings and determine whether the adverse hemodynamic responses we observed contribute to the high prevalence of SCD that firefighters experience on the job.
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Microplastics (MPs), emerging contaminants, are easily transported and enriched in the kidney, suggesting the kidney is susceptible to the toxicity of MPs. In this study, we explored the toxicity of MPs, including unmodified polystyrene (PS), negative-charged PS-SO3H, and positive-charged PS-NH2 MPs, in mice models for 28 days at a human equivalent concentration. The results showed MPs significantly increased levels of UREA, urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) levels in serum and white blood cells, protein, and microalbumin in urine. In the kidney, MPs triggered persistent inflammation and renal fibrosis, which was caused by the increased senescence of tubular epithelial cells. Moreover, we identified the critical role of the Klotho/Wnt/ß-catenin signaling pathway in the process of MPs induced senescence of tubular epithelial cells, promoting the epithelial-mesenchymal transformation of epithelial cells. MPs supported the secretion of TGF-ß1 by senescent epithelial cells and induced the activation of renal fibroblasts. On the contrary, restoring the function of Klotho can alleviate the senescence of epithelial cells and reverse the activation of fibroblasts. Thus, our study revealed new evidence between MPs and renal fibrosis, and adds an important piece to the whole picture of the plastic pollution on people's health.
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Senescencia Celular , Células Epiteliales , Fibrosis , Microplásticos , Poliestirenos , Animales , Microplásticos/toxicidad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Senescencia Celular/efectos de los fármacos , Poliestirenos/toxicidad , Ratones , Glucuronidasa/metabolismo , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Túbulos Renales/metabolismo , Proteínas Klotho , Masculino , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Humanos , Línea Celular , Vía de Señalización Wnt/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Ratones Endogámicos C57BL , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacosRESUMEN
This study investigates the effects of chlorine dioxide (ClO2) disinfection on the community structure, regrowth potential, and metabolic product secretion of disinfection-residual bacteria (DRB) in secondary effluent (SE), denitrification filter effluent (DFE), and ultrafiltration effluent (UE). Results show that ClO2 effectively reduces bacteria in SE and UE, achieving log removal values exceeding 3 at 1 mg/L within 30 min. A salient positive correlation (R2 > 0.95) exists between changes in total fluorescence intensity and disinfection efficacy. Post-treatment, Acinetobacter abundance increased in SE, while Pseudomonas decreased in DFE and UE. At lower ClO2 concentrations, Staphylococcus, Mycobacterium, Aeromonas, and Lactobacillus increased in DFE, but decreased at higher concentrations. After storage, bacterial counts in disinfected samples exceeded those in the control group, surpassing 105 CFU/mL. Despite an initial decline, species richness and evenness partially recovered but remained lower than control levels. Culturing DRB for 72 h showed elevated extracellular polymeric substances (EPS) secretion, quantified as total organic carbon (TOC), ranging from 5 to 27 mg/L, with significantly higher EPS in the disinfection group. Parallel factor analysis with self-organizing maps (PARAFAC-SOM) effectively differentiated water sample types and EPS fluorescent substances, underscoring the potential of three-dimensional fluorescence as an indirect measure of ClO2 disinfection efficacy.
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Bacterias , Compuestos de Cloro , Desinfectantes , Desinfección , Óxidos , Purificación del Agua , Compuestos de Cloro/farmacología , Óxidos/farmacología , Desinfección/métodos , Desinfectantes/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Bacterias/metabolismo , Purificación del Agua/métodos , Microbiología del AguaRESUMEN
Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5-41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0-21.5%; difference of 17.6%, 95% CI 11.6-23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of - 0.3% (95% prediction interval - 17.0-16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.
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Depresión , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Escalas de Valoración Psiquiátrica , Humanos , Prevalencia , Anciano , Femenino , Depresión/epidemiología , Depresión/diagnóstico , Masculino , Evaluación Geriátrica/métodos , Anciano de 80 o más Años , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/diagnósticoRESUMEN
Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.
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In navigating the complexities of social life, humans have evolved to interpret invisible odorous chemical cues, with profound behavioural impacts often unbeknown to the conscious mind. The manifestation of this in humans is evident in the scent of androstadienone (androsta-4,16-dien-3-one), an odorous compound which is considered a putative human pheromone. The current study investigated the effect of androstadienone on social distance-dependent prosocial behaviour measured by a social discounting task, in which participants chose between selfish and generous options. Based on our pre-registration, we predicted a sex-specific effect, with males exposed to androstadienone exhibiting increased generosity, while females would choose more selfishly. Employing a double-blind, placebo-controlled, between-subject design, we recruited 170 participants who were randomly assigned to either the androstadienone or control condition. Olfactory stimuli were administered while participants completed the social discounting task. Inconsistent with our hypothesis, inhaling androstadienone did not impact social distance-dependent prosocial behaviour. This finding was supported by multiple estimates of prosociality, including model-free, model-based and maximum likelihood estimation. Further analyses indicated that androstadienone administration did not influence perceived social distance or bias participants towards being generous or selfish. Thus, our empirical findings provide no support for the hypothesis that androstadienone modulates generosity.
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Objective: Previous studies have suggested diet was associated with depressive symptoms. We aimed to develop and validate Dietary Depression Index (DDI) based on dietary prediction of depression in a large Chinese cancer screening cohort.Methods: In the training set (n = 2729), we developed DDI by using intake of 20 food groups derived from a food frequency questionnaire to predict depression as assessed by Patient Health Questionnaire-9 based on the reduced rank regression method. Sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the performance of DDI in evaluating depression in the validation dataset (n = 1176).Results: Receiver operating characteristic analysis was constructed to determine the best cut-off value of DDI in predicting depression. In the study population, the DDI ranged from -3.126 to 1.810. The discriminative ability of DDI in predicting depression was good with the AUC of 0.799 overall, 0.794 in males and 0.808 in females. The best cut-off values of DDI for depression prediction were 0.204 overall, 0.330 in males and 0.034 in females. DDI was a validated method to assess the effects of diet on depression.Conclusion: Among individual food components in DDI, fermented vegetables, fresh vegetables, whole grains and onions were inversely associated, whereas legumes, pickled vegetables and rice were positively associated with depressive symptoms.
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Chlorination is the most widely used disinfection technology due to its simplicity and continuous disinfection ability. However, the drawbacks of disinfection by-products and chlorine-resistant bacteria have gained increasing attention. Nowadays, ferrate (Fe(VI)) is a multifunctional and environmentally friendly agent which has great potential in wastewater reclamation and reuse. This study investigated synergistic Fe(VI) and chlorine technology for reclaimed water disinfection in terms of microbial control and chlorine decay mitigation. Specifically, synergistic disinfection significantly improved the inactivation efficiency on total coliform, Escherichia coli and heterotrophic bacteria compared to sole chlorination. Synergistic disinfection also exhibited superior performance on controlling the relative abundance of chlorine-resistant bacteria and pathogenic bacteria. In addition, the decay rate of residual chlorine was relatively lower after Fe(VI) pretreatment, which was beneficial for microbial control during the reclaimed water distribution process. Technical and economic analyses revealed that synergistic Fe(VI) and chlorine disinfection was suitable and feasible. Results of this study are believed to provide useful information and alternative options on the optimization of reclaimed water disinfection.
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Cloro , Desinfección , Hierro , Eliminación de Residuos Líquidos , Purificación del Agua , Cloro/farmacología , Desinfección/métodos , Purificación del Agua/métodos , Eliminación de Residuos Líquidos/métodos , Desinfectantes/farmacología , Aguas Residuales/microbiología , Escherichia coli/efectos de los fármacos , Microbiología del AguaRESUMEN
This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.
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Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.
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Bencilisoquinolinas , Barrera Hematoencefálica , Células Endoteliales , Accidente Cerebrovascular Isquémico , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Piroptosis , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Piroptosis/efectos de los fármacos , Ratones , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/patología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Bencilisoquinolinas/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacologíaRESUMEN
The black soldier fly (BSF, Hermetia illucens) is a resource insect that can utilize livestock and poultry feces. However, BSFs may also increase the risk of transmission of antibiotic resistance genes (AGRs) that are widespread in livestock and poultry farm environments. Therefore, we aimed to evaluate the biosecurity risks of different BSF treatments in the laying chicken food chain using the "chicken manure-BSF-laying hens" model. Our results indicated that different BSF treatments significantly affected antibiotic residue, ARGs, MGEs, bacterial antibiotic resistance, and bacterial microbial community composition in the food chain of laying hens fed BSFs. These risks can be effectively reduced through starvation treatment and high-temperature grinding treatment. Comprehensive risk assessment analysis revealed that starvation combined with high-temperature milling (Group H) had the greatest effect.
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Alimentación Animal , Antibacterianos , Pollos , Dieta , Doxiciclina , Animales , Alimentación Animal/análisis , Femenino , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Dieta/veterinaria , Simuliidae/efectos de los fármacos , Dípteros/efectos de los fármacosRESUMEN
Encapsulating enzymes within metal-organic frameworks such as zeolitic imidazolate framework-8 (ZIF-8) has been demonstrated to enhance enzymatic performance under harsh conditions. However, by computer-aided analysis, we revealed that highly hydrophobic organic ligands and unfavorable metal ions could greatly impair the activity of haloalkane dehalogenase DhaA by directly interacting with the catalytic sites, causing an extremely low activity of DhaA after encapsulating within ZIF-8. We also found that the presence of a protecting polymer could protect DhaA from the damage of organic ligands and metal ions and that a positively charged amino acid could increase the DhaA activity. Based on the simulations and experimental observations, we have designed to coencapsulate DhaA with poly(vinylpyrrolidone) (PVP) and lysine (Lys) within the amorphous Co-based metal azolate coordination polymer (CoCP). The as-prepared immobilized enzyme (DhaA/PVP/Lys@CoCP) exhibited significantly increased activity (91.5 times higher than that of DhaA@ZIF-8), dramatically enhanced thermostability at 50-70 °C, greatly improved catalytic performance in several organic solvent solutions, and good recyclability (over 75% of the initial activity after 10 cycles). The superiority of the immobilized enzyme was also demonstrated with a substrate frequently detected in the real world. In addition to the protective effect of PVP and positive effect of Lys, experimental and computational investigations unveiled other two favorable aspects that contributed to the enhanced enzymatic performance: (1) high hydrophilicity of the immobilization material and (2) the use of Co2+ with a minimal negative effect on DhaA. The research has thus provided a promising immobilized DhaA with favorable catalytic performance and great potential in industrial applications.
Asunto(s)
Enzimas Inmovilizadas , Hidrolasas , Interacciones Hidrofóbicas e Hidrofílicas , Estructuras Metalorgánicas , Hidrolasas/química , Hidrolasas/metabolismo , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Estructuras Metalorgánicas/química , Polímeros/químicaRESUMEN
OBJECTIVES: To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables. STUDY DESIGN AND SETTING: This was a secondary analysis of data from an IPDMA on the depression screening accuracy of the GDS. Datasets from studies published in any language were eligible for the present study if they included GDS-15 scores for participants aged 60 or older. MDC of the GDS-15 was estimated via random-effects meta-analysis using 2.77 (MDC95) and 1.41 (MDC67) standard errors of measurement. Subgroup analyses were used to evaluate differences in MDC by participant age and sex. Meta-regression was conducted to assess for differences based on study-level variables, including mean age, proportion male, proportion with major depression, and recruitment setting. RESULTS: 5876 participants (mean age 76 years, 40% male, 11% with major depression) from 21 studies were included. The MDC95 was 3.81 points (95% confidence interval [CI] 3.59, 4.04), and MDC67 was 1.95 (95% CI 1.83, 2.03). The difference in MDC95 was 0.26 points (95% CI 0.04, 0.48) between ≥80-year-olds and <80-year-olds; MDC95 was similar for females and males (0.05, 95% CI -0.12, 0.22). The MDC95 increased by 0.29 points (95% CI 0.17, 0.41) per 10% increase in proportion of participants with major depression; mean age had a small association (0.04 points, 95% CI 0.00 to 0.09) with MDC95, but sex and recruitment setting were not significantly associated. CONCLUSION: The MDC95 was 3.81 points and MDC67 was 1.95 points. MDC95 increased with the proportion of participants with major depression. Results can be used to evaluate individual changes in depression symptoms and as a threshold for assessing minimal clinical important difference estimates.
RESUMEN
The model of M2-like tumor-associated macrophages (TAMs) is an increasingly attractive model for the study of TAMs. However, the detailed process of M2-like TAMs polarization induced by lactic acid or conditioned medium from Lewis cells (LCM) and the identification of M2-like TAMs is not yet available. In this protocol, we present the detailed methods to induce M2-like TAMs polarization and verify its functionality in order to better carry out related research. For complete details on the use and execution of this protocol, please refer to Fang et al.1.