Changes In Function Research Articles

Validation of Korean Olfactory Questionnaire for Perioperative Olfactory Assessment in Endoscopic Endonasal Skull Base Surgery.

Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery.

Chronic Liver Disease and Promising Therapeutic Strategy: A Concise Review

Abstract Background: Chronic liver dysfunction (CLD) is a significant global health issue; alcohol use, obesity, drugs, and antibiotic and viral infections contribute to its development. However, changes in gut microbiota composition, primarily as people grow older, can also play a role in initiating and progressing liver dysfunction. Purpose: This review summarizes the altered gut microbiota–mediated chronic liver dysfunction and promising therapeutic strategies for NAFLD, ALD, NASH, and liver cirrhosis. Discussion on the chronic liver disease and its therapeutic aspects: The gut microbiota influences physiological processes, including immune system regulation, by promoting the production of pro-inflammatory markers and elevating the expression of toll-like receptors (TLRs) on hepatocytes, metabolisms of bile acids and choline, alteration in saturated aliphatic organic acid (SCFA) production, and food absorption. These alterations increase intestinal permeability, chronic inflammation, and liver dysfunction. Dysbiosis triggers inflammatory pathways, oxidative stress, and the production of toxic compounds that damage liver cells and promote chronic liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and cirrhosis. Age-related changes in gut motility, secretory function, and immunological function can further decline beneficial bacterial diversity and abundance and shifts in pathogenic bacterial species’ relative abundance. Conclusion: Dysbiosis resulting from these age-related changes may contribute to the development of CLD. Numerous therapeutic approaches are available to restore the altered gut microbiota and reduce the risk of chronic liver dysfunction.

Level0 to Level1B processor for MethaneAIR

Abstract. This work presents the development of the MethaneAIR Level0–Level1B processor, which converts raw L0 data to calibrated and georeferenced L1B data. MethaneAIR is the airborne simulator for MethaneSAT, a new satellite under development by MethaneSAT LLC, a subsidiary of the Environmental Defense Fund (EDF). MethaneSAT's goals are to precisely map over 80 % of the production sources of methane from oil and gas fields across the globe to an accuracy of 2–4 ppb on a 2 km2 scale. Efficient algorithms have been developed to perform dark corrections, estimate the noise, radiometrically calibrate data, and correct stray light. A forward model integrated into the L0–L1B processor is demonstrated to retrieve wavelength shifts during flight accurately. It is also shown to characterize the instrument spectral response function (ISRF) changes occurring at each sampled spatial footprint. We demonstrate fast and accurate orthorectification of MethaneAIR data in a three-step process: (i) initial orthorectification of all observations using aircraft avionics, a simple camera model, and a medium-resolution digital elevation map; (ii) registration of oxygen (O2) channel grayscale images to reference Multispectral Instrument (MSI) band 11 imagery via Accelerated-KAZE (A-KAZE) feature extraction and linear transformation, with similar co-registration of methane (CH4) channel grayscale images to the registered O2 channel images; and finally (iii) optimization of the aircraft position and attitude to the registered imagery and calculation of viewing geometry. This co-registration technique accurately orthorectifies each channel to the referenced MSI imagery. However, in the pixel domain, radiance data for each channel are offset by almost 150–200 across-track pixels (rows) and need to be aligned for the full-physics or proxy retrievals where both channels are simultaneously used. We leveraged our orthorectification tool to identify tie points with similar geographic locations in both CH4 and O2 images in order to produce shift parameters in the across-track and along-track dimensions. These algorithms described in this article will be implemented into the MethaneSAT L0–L1B processor.

A Glimpse of Urine Stromal Cells-Derived Exosomes Containing Deleted in Malignant Brain Tumors 1: A Critical Factor in Wound Healing

Exosomes are small extracellular vesicles released by a range of cells, including mesenchymal stromal/stem cells (MSCs), immune cells, cancerous cells, etc. These particles contain biomolecules such as DNA, microRNA, messenger RNA, protein, and lipid, and play a vital role in establishing cellular communication. After reaching the target cells, the particles cause changes in function, fate, morphology, differentiation, and growth. Exosomes released from a variety of sources have the ability to influence the behavior of cells involved in wound healing, enhance neovascularization, promote collagen deposition, reduce inflammation, and quicken the healing process. According to new research, endothelial cell adhesion, migration, proliferation, vascular repair, and angiogenesis are all accelerated during the wound healing process when deleted in malignant brain tumors 1 (DMBT1) is used as an active stimulant. This article will review DMBT1 protein as one of the major elements of exosomes from human urine-derived MSCs.

Leveraging historic streamflow and weather data with deep learning for enhanced streamflow predictions

ABSTRACT Streamflow information is crucial for effectively managing water resources. The declining number of active gauging stations in many rivers is a global concern, necessitating the need for reliable streamflow estimates. Deep learning techniques offer potential solutions, but their application in southern Africa remains largely underexplored. To fill this gap, this study evaluated the predictive performance of gated recurrent unit (GRU) and long short-term memory (LSTM) networks using two headwater catchments of the Steelpoort River, South Africa, as case studies. The model inputs included rainfall, maximum, and minimum temperature, as well as past streamflow, which was utilized in an autoregressive sense. The inclusion of streamflow in this way allowed for the incorporation of simulated streamflow values into the look-back window for predicting the streamflow of the testing set. Two modifications were required to the GRU and LSTM architectures to ensure physically consistent predictions, including a change in the activation function of the GRU/LSTM cells in the final hidden layer, and a non-negative constraint that was used in the dense layer. Models trained using commercial weather station data produced reliable streamflow estimates, while moderately accurate predictions were obtained using freely available gridded weather data.

Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations.

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.

Using Speckle Tracking Analysis, Does Age Affect RV Longitudinal Strain?

Introduction: The right ventricle (RV) is increasingly crucial in clinical settings, but traditional echocardiography is challenging to evaluate its function. Advanced techniques like speckle tracking improve RV functional assessment. According to previous studies, RV free wall longitudinal strain measurements vary with age necessitating further research. Aim: This study aimed to evaluate the effects of age on RV longitudinal strain using speckle tracking (ST) analysis. Methods: 103 healthy adult volunteers, mean age 37.1±11.9 years (range: 20-66), underwent comprehensive speckle tracking analysis, to determine age-related changes in RV dimensions and function. Results: showed a significant decrease in global and segmental (basal, mid, and apical) FWLS with age (p < .001). Conclusion: These significant differences in free wall longitudinal strains among age groups by 2D-ST analysis indicate the need for age-adjusted measures in RV function evaluation. Conventional techniques may ignore minor changes, leading to underestimated RV function assessment. The findings also suggest that advanced techniques allow early identification of RV dysfunction by detecting subclinical dysfunction before anomalies revealed by traditional echocardiography occur.

The Impact of Aging on Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system. Age is one of the most important factors in determining MS phenotype. This review provides an overview of how age influences MS clinical characteristics, pathology, and treatment. New methods for measuring aging have improved our understanding of the aging process in MS. New studies have characterized the molecular and cellular composition of chronic active or smoldering plaques in MS. These lesions are important contributors to disability progression in MS. These studies highlight the important role of immunosenescence and the innate immune system in sustaining chronic inflammation. Given these changes in immune function, several studies have assessed optimal treatment strategies in aging individuals with MS. MS phenotype is intimately linked with chronologic age and immunosenescence. While there are many unanswered questions, there has been much progress in understanding this relationship which may lead to more effective treatments for progressive disease.

Long-term bowel functional outcomes following anal sphincter-preserving surgery for upper and middle rectal cancer: a single-center longitudinal study.

Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients' quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.

Passive heating-induced changes in muscle contractile function are not further augmented by prolonged exposure in young males experiencing moderate thermal stress.

Background: We investigated the impact of 1) passive heating (PH) induced by single and intermittent/prolonged hot-water immersion (HWI) and 2) the duration of PH, on muscle contractile function under the unfatigued state, and during the development of muscle fatigue. Methods: Twelve young males volunteered for this study consisting of two phases: single phase (SP) followed by intermittent/prolonged phase (IPP), with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and HWI (44-45°C; water up to the waist level). SP-HWI included one continuous 45-min bath (from 15 to 60min). IPP-HWI included an initial 45-min bath (from 15 to 60min) followed by eight additional 15-min baths interspaced with 15-min breaks at room temperature between 75 and 300min. Intramuscular (Tmu; measured in the vastus lateralis muscle) and rectal (Trec) temperatures were determined. Neuromuscular testing (performed in the knee extensors and flexors) was performed at baseline and 60min later during SP, and at baseline, 60, 90, 150 and 300min after baseline during IPP. A fatiguing protocol (100 electrical stimulations of the knee extensors) was performed after the last neuromuscular testing of each trial. Results: HWI increased Tmu and Trec to 38°C-38.5°C (p < 0.05) during both SP and IPP. Under the unfatigued state, HWI did not affect electrically induced torques at 20Hz (P20) and 100Hz (P100). However, it induced a shift towards a faster contractile profile during both SP and IPP, as evidenced by a decreased P20/P100 ratio (p < 0.05) and an improved muscle relaxation (i.e., reduced half-relaxation time and increased rate of torque relaxation; p < 0.05). Despite a reduced voluntary activation (i.e., -2.63% ± 4.19% after SP-HWI and -5.73% ± 4.31% after IPP-HWI; condition effect: p < 0.001), HWI did not impair maximal isokinetic and isometric contraction torques. During the fatiguing protocol, fatigue index and the changes in muscle contractile properties were larger after HWI than CON conditions (p < 0.05). Finally, none of these parameters were significantly affected by the heating duration. Conclusion: PH induces changes in muscle contractile function which are not augmented by prolonged exposure when thermal stress is moderate.

Alterations in the molecular control of mitochondrial turnover in COPD lung and airway epithelial cells

Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4–7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established.

Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer's disease.

Impaired brain bioenergetics is a pathological hallmark of Alzheimer's disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition. The Creatine to Augment Bioenergetics in Alzheimer's disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size. CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8weeks. CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials. ClinicalTrials.gov, NCT05383833 , registered on 20 May 2022.

Transcranial direct current stimulation for chronic headaches, a randomized, controlled trial.

Chronic headaches are a frequent cause of pain and disability. The purpose of this randomized trial was to examine whether transcranial direct current stimulation (tDCS) applied to the primary motor cortex, reduces pain and increases daily function in individuals suffering from primary chronic headache. A prospective, randomized, controlled trial, where participants and assessors were blinded, investigated the effect of active tDCS vs. sham tDCS in chronic headache sufferers. Forty subjects between 18 and 70 years of age, with a diagnosis of primary chronic headache were randomized to either active tDCS or sham tDCS treatment groups. All patients received eight treatments over four consecutive weeks. Anodal stimulation (2 mA) directed at the primary motor cortex (M1), was applied for 30 min in the active tDCS group. Participants in the sham tDCS group received 30 s of M1 stimulation at the start and end of the 30-minute procedure; for the remaining 29 min, they did not receive any stimulation. Outcome measures based on data collected at baseline, after eight treatments and three months later included changes in daily function, pain levels, and medication. Significant improvements in both daily function and pain levels were observed in participants treated with active tDCS, compared to sham tDCS. Effects lasted up to 12 weeks post-treatment. Medication use remained unchanged in both groups throughout the trial with no serious adverse effects reported. These results suggest that tDCS has the potential to improve daily function and reduce pain in patients suffering from chronic headaches. Larger randomized, controlled trials are needed to confirm these findings. The study was approved by the local ethics committee (2018/2514) and by the Norwegian Centre for Research Data (54483).

Dual-task turn velocity - a novel digital biomarker for mild cognitive impairment and dementia.

Disorders associated with cognitive impairment impose a significant burden on both families and society. Previous studies have indicated that gait characteristics under dual-task as reliable markers of early cognitive impairment. Therefore, digital gait detection has great potential for future cognitive screening. However, research on digital biomarkers based on smart devices to identify cognitive impairment remains limited. The aim of this study is to explore digital gait biomarkers by utilizing intelligent wearable devices for discriminating mild cognitive impairment and dementia. This study included 122 subjects (age: 74.7 ± 7.7 years) diagnosed with normal cognition (NC, n = 38), mild cognitive impairment (MCI, n = 42), or dementia (n = 42). All subjects underwent comprehensive neuropsychological assessments and cranial Magnetic Resonance Imaging (MRI). Gait parameters were collected using validated wearable devices in both single-task and dual-task (DT). We analyzed the ability of gait variables to predict MCI and dementia, and examined the correlations between specific DT-gait parameters and sub-cognitive functions as well as hippocampal atrophy. Our results demonstrated that dual-task could significantly improve the ability to predict cognitive impairment based on gait parameters such as gait speed (GS) and stride length (SL). Additionally, we discovered that turn velocity (TV and DT-TV) can be a valuable novel digital marker for predicting MCI and dementia, for identifying MCI (DT-TV: AUC = 0.801, sensitivity 0.738, specificity 0.842), and dementia (DT-TV: AUC = 0.923, sensitivity 0.857, specificity 0.842). The correlation analysis and linear regression analysis revealed a robust association between DT-TV and memory function, as well as the hippocampus atrophy. This study presents a novel finding that DT-TV could accurately identify varying degrees of cognitive impairment. DT-TV is strongly correlated with memory function and hippocampus shrinkage, suggests that it can accurately reflect changes in cognitive function. Therefore, DT-TV could serve as a novel and effective digital biomarker for discriminating cognitive impairment.

Is Early-Life Enrichment Associated With Better Cognitive Function Among Older Adults? Examining Home and School Environments.

Objectives: We examine whether early-life enrichment, involving varied and stimulating activities to enhance cognitive function during childhood and adolescence, is associated with cognitive function in later life and whether the benefits persist over time. Methods: Growth curve models were used to examine up to five waves of data from the Health and Retirement Study-a nationally representative survey of adults 50years and older (N = 10,070). We constructed separate measures of early-life enrichment to distinguish sources of influence (i.e., enriched home environment and enriched school environment). Global cognitive function was assessed with a modified version of the Telephone Interview for Cognitive Status. Results: Greater enrichment in each environment was incrementally associated with better cognitive function at baseline, but enrichment was not associated with change in cognitive function over time. Discussion: Receiving enrichment from multiple environments during sensitive periods of cognitive development may be advantageous for cognitive functioning in later life.

Analysis of the influence of ions on degradation of benzamide with hydrodynamic cavitation technology

In recent years, hydrodynamic cavitation technology has become a research hotspot in various fields. This study establishes a benzamide model with different ion types, ion concentrations, and bubble radii. The model is used to study the diffusivity of water molecules on the benzamide wall and structural changes in benzamide. The influence of ion type, ion concentration, and bubble radius on the degradation of pollutants is examined. The results are as follows: the larger the bubble radius and ion concentration, the larger the rate of change of maximum radial distribution function of carbon atoms (w). The effect of ion type on the diffusion coefficient of water molecules on the benzamide wall is as follows: H2O2 > HCO3−1 > NO3−1. In terms of structural changes in the benzamide, in the model containing H2O2, ion concentration has a greater effect than bubble radius. In the model containing HCO3−1, bubble radius has a greater effect than ion concentration. In the model containing NO3−1, bubble radius and ion concentration have an equal effect. w decreases most in the model containing H2O2 and least in the model containing NO3−1. The model containing H2O2 produces the most powerful effect in benzamide pollutant degradation. This study provides technical guidance and a theoretical basis for the green treatment of pollutants using cavitation theory.

A study protocol to investigate if acipimox improves muscle function and sarcopenia: an open-label, uncontrolled, before-and-after experimental medicine feasibility study in community-dwelling older adults

IntroductionSarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD...

Neuroprotective effects of polyphyllin VI against rotenone-induced toxicity in SH-SY5Y cells

BackgroundA substantial body of evidence is drawing connections between Parkinson's disease (PD) and the phenomena of oxidative stress and mitochondrial dysfunction. Polyphyllin VI (PPVI), an active compound found in Rhizoma Paridis-commonly known as Chonglou (CL) in China, has been identified for its various pharmacological properties, including anti-tumor and anti-inflammatory effects. ObjectiveIn the present study, an in vitro model of PD was established by treating SH-SY5Y cells with rotenone (ROT), to evaluate the potential neuroprotective effects of polyphyllin VI and its underlying mechanism. MethodsSH-SY5Y cells were treated with ROT to establish an in vitro model of PD. The effects of polyphyllin VI on cell viability were assessed using the resazurin assay. Cell morphology was examined using a microscope. The YO-PRO-1/PI was used to detect apoptosis. Mito-Tracker Red CMXRos, Mito-Tracker Green, and JC-1 were used to detect the effects of polyphyllin Ⅵ on mitochondrial viability, morphology, and function. Oxidative stress-related marker detection kits were used to identify the effects of polyphyllin VI on oxidative stress. Western blot analysis was employed to investigate the signaling pathways associated with neuroprotection. ResultsPPVI increased ROT-induced SH-SY5Y cell viability and improved ROT-induced cellular morphological changes. PPVI ameliorated ROT-induced oxidative stress status, and attenuated mitochondrial function and morphological changes. PPVI may exert neuroprotective effects through FOXO3α/CREB1/DJ-1-related signaling pathways. ConclusionThese preliminary findings suggested that PPVI possesses neuroprotective attributes in vitro, and it may be a potential candidate for PD treatment. However, extensive research is necessary to fully understand the mechanisms of PPVI and its effectiveness both in vitro and in vivo.

The Correlation between Metal Mixed Exposure and Lung Function in Different Ages of the Population.

Herein, we explored the overall association between metal mixtures and lung functions in populations of varying ages and the relationship among the associated components. The 2007-2012 National Health and Nutrition Examination Survey data of 4382 American participants was analyzed, and generalized linear, elastic net, quantile g-computation, and Bayesian kernel machine regression models were used to evaluate the relationship between exposure to the metal mixture and lung function at various ages. The results of barium exposure at distinct stages revealed that children and adolescents exhibited greater lung function changes than those in adults and the elderly. Additionally, compared with children and adolescents, cadmium- and arsenic-containing metabolites contributed to nonconductive lung function changes in adults and the elderly exposed to metal mixtures. The results showed that the effects of exposure to metal mixtures on lung function in children and adolescents were predominantly caused by lead and barium. Altogether, children and adolescents were found to be more susceptible to metal-exposure-mediated lung function changes than adults and the elderly.

Single-cell transcriptomics reveal the remodeling landscape of bladder in patients with obstruction-induced detrusor underactivity.

Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients' bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single-cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re-cluster analysis revealed an accumulation of the RBFOX1+ fibroblasts and RIPOR2+ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single-cell atlas for obstruction-induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.