The NONRATT023402.2/rno-miR-3065-5p/NGFR axis affects levodopa-induced dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson's disease. However, few studies have focused on the pathogenesis of LID at the transcriptional level. NONRATT023402.2, a long non-coding RNA (lncRNA) that may be related to LID was discovered in our previous study and characterized in rat models of LID. In the present study, NONRATT023402.2 was overexpressed by injection of adeno-associated virus (AAV) in striatum of LID rats, and 48 potential target genes, including nerve growth factor receptor (NGFR) were screened using next-generation sequencing and target gene predictions. The NONRATT023402.2/rno-miR-3065-5p/NGFR axis was verified using a dual luciferase reporter gene. Overexpression of NONRATT023402.2 significantly increased the abnormal involuntary movements (AIM) score of LID rats, activated the PI3K/Akt signaling pathway, and up-regulated c-Fos in the striatum. NGFR knockdown by injection of ShNGFR-AAV into the striatum of LID rats resulted in a significant decrease in the PI3K/Akt signaling pathway and c-Fos expression. The AIM score of LID rats was positively correlated with the expressions of NONRATT023402.2 and NGFR. A dual luciferase reporter assay showed that c-Fos, as a transcription factor, bound to the NONRATT023402.2 promoter and activated its expression. Together, the results showed that NONRATT023402.2 regulated NGFR expression via a competing endogenous RNA mechanism, which then activated the PI3K/Akt pathway and promoted c-Fos expression. This suggested that c-Fos acted as a transcription factor to activate NONRATT023402.2 expression, and form a positive feedback regulation loop in LID rats, thus, aggravating LID symptoms. NONRATT023402.2 is therefore a possible novel therapeutic target for LID.

Unlocking potential: low frequency subthalamic nucleus stimulation enhances executive function in Parkinson's disease patients with postural instability/gait disturbance.

Postural instability/gait disturbance (PIGD) is very common in advanced Parkinson's disease, and associated with cognitive dysfunction. Research suggests that low frequency (5-12 Hz) subthalamic nucleus-deep brain stimulation (STN-DBS) could improve cognition in patients with Parkinson's disease (PD). However, the clinical effectiveness of low frequency stimulation in PIGD patients has not been explored. This study was designed in a double-blinded randomized cross-over manner, aimed to verify the effect of low frequency STN-DBS on cognition of PIGD patients. Twenty-nine PIGD patients with STN-DBS were tested for cognitive at off (no stimulation), low frequency (5 Hz), and high frequency (130 Hz) stimulation. Neuropsychological tests included the Stroop Color-Word Test (SCWT), Verbal fluency test, Symbol Digital Switch Test, Digital Span Test, and Benton Judgment of Line Orientation test. For conflict resolution of executive function, low frequency stimulation significantly decreased the completion time of SCWT-C (p = 0.001) and Stroop interference effect (p < 0.001) compared to high frequency stimulation. However, no significant differences among stimulation states were found for other cognitive tests. Here we show, low frequency STN-DBS improved conflict resolution of executive function compared to high frequency. Our results demonstrated the possibility of expanding the treatment coverage of DBS to cognitive function in PIGD, which will facilitate integration of low frequency stimulation into future DBS programming.

Oat bran prevents high-fat-diet induced muscular dysfunction, systemic inflammation and oxidative stress through reconstructing gut microbiome and circulating metabolome.

Western-type diet characterized by high fat emerges a promoter of skeletal muscle dysfunctions. Oat bran was typically considered a healthy food of premium quality for its abundant dietary fiber. The present study comprehensively explored the effects of a diet rich in oat bran on skeletal muscle disfunctions in high-fat diet (HFD) fed mice. Dietary-fiber-rich oat bran significantly ameliorated HFD-induced skeletal muscle function abnormalities, as evidenced by a phenotype improvement in mice grip strength and endurance treadmill running distance, accompanied with the regulation of muscle functions related gene expressions, namely Fis1, Cytc, Mhy2 and Mhy4. Oat bran suppressed the production of systemic inflammatory cytokines while promoted superoxide dismutase and glutathione. Furthermore, oat bran significantly impacted gut microbiota composition by promoting short chain fatty acids (SCFAs) producers and certain probiotic genera, along with the enhancement of SCFAs. Oat bran also significantly decreased the circulating levels of inflammation-related metabolites and played roles in MAPK signaling, thereafter influencing skeletal muscle functions. Collectively, benefits from integration of biomedical indicators, microbiomics, and metabolomics demonstrates the benefits of oat bran consumption on prevention of HFD-related muscular dysfunctions via alleviating HFD-induced inflammation, gut dysbiosis, and systemic metabolism, pinpointing a novel mechanism underlying the muscle-promoting property of oat bran.

3-Monochloropropane-1,2-diol reduced bioaccessibility of sn-2 palmitate via bounding with pancreatic lipase in infant formula during gastrointestinal digestion.

Infant formula contains 3-monochloropropane-1,2-diol esters which are formed during the deodorization step of vegetable oils refining. European Food Safety Authority stated that 3-monochloropropane-1,2-diol esters can be hydrolyzed in the gastrointestinal tract to free-form 3-monochloropropane-1,2-diol, which has potential toxicity and can be rapidly absorbed. Evaluating the effect of 3-monochloropropane-1,2-diol on nutrition absorption is a prerequisite for establishing effective management strategies. A total of 66 crucial lipid molecules associated with 3-monochloropropane-1,2-diol were identified based on Debiased Sparse Partial Correlation analysis. 3-Monochloropropane-1,2-diol affected triglyceride hydrolyzation and increased the concentration of undigested sn-2 palmitate (9.57 to 17.06 mg kg-1). 3-Monochloropropane-1,2-diol reduced the bioaccessibility of fatty acids and more short- (31.42 to 58.02 mg kg-1) and medium-chain fatty acids (17.03 to 26.43 mg kg-1) remained unabsorbed. Lipidomics profiles of infant formula models spiked with different 3-MCPDE levels were investigated and the results were consistent with the experiments with the commercial formula indicating lipid alteration was mainly affected by the digestive 3-MCPD. The formation of 3-monochloropropane-1,2-diol ester-pancreatic lipase with the binding energy of -4.9 kcal mol-1 was more stable than triglyceride-pancreatic lipase (-4.0 kcal mol-1), affecting triglyceride hydrolyzation. 3-Monochloropropane-1,2-diol was bound to Glu13 and Asp331 residues of the pancreatic lipase via hydrogen bonds, which resulted in a conformational change of pancreatic lipase and spatial shielding effect. The existence of the spatial shielding effect reduced the accessibility of pancreatic lipase and further affected triglyceride hydrolyzation. These findings indicated that 3-monochloropropane-1,2-diol obstructed nutrient acquisition and laid the foundation for the subsequent nutrition enhancement design.

Neutrophil extracellular traps aggravate intestinal epithelial necroptosis in ischaemia-reperfusion by regulating TLR4/RIPK3/FUNDC1-required mitophagy.

Neutrophil extracellular trap (NET) has been confirmed to be related to gut barrier injury during intestinal ischaemia-reperfusion (II/R). However, the specific molecular regulatory mechanism of NETs in II/R-induced intestinal barrier damage has yet to be fully elucidated. Here, we reported increased NETs infiltration accompanied by elevated inflammatory cytokines, cellular necroptosis and tight junction disruption in the intestine of human II/R patients. Meanwhile, NETs aggravated Caco-2 intestinal epithelial cell necroptosis, impairing the monolayer barrier in vitro. Moreover, Pad4-deficient mice were used further to validate the role of NETs in II/R-induced intestinal injury. In contrast, NET inhibition via Pad4 deficiency alleviated intestinal inflammation, attenuated cellular necroptosis, improved intestinal permeability, and enhanced tight junction protein expression. Notably, NETs prevented FUN14 domain-containing 1 (FUNDC1)-required mitophagy activation in intestinal epithelial cells, and stimulating mitophagy attenuated NET-associated mitochondrial dysfunction, cellular necroptosis, and intestinal damage. Mechanistically, silencing Toll-like receptor 4 (TLR4) or receptor-interacting protein kinase 3 (RIPK3) via shRNA relieved mitophagy limitation, restored mitochondrial function and reduced NET-induced necroptosis in Caco-2 cells, whereas this protective effect was reversed by TLR4 or RIPK3 overexpression. The regulation of TLR4/RIPK3/FUNDC1-required mitophagy by NETs can potentially induce intestinal epithelium necroptosis.

Robust noncovalent spherical nucleic acid enzymes (SNAzymes) for ultrasensitive unamplified electrochemiluminescence detection of endogenous myocardial MicroRNAs.

Here we develop robust noncovalent spherical nucleic acid enzymes (SNAzymes) for direct electrochemiluminescence (ECL) detection of acute myocardial infarction (AMI) related endogenous microRNAs in both circulating blood and cardiomyocytes, which circumvents the need for time-consuming signal amplification widely used in previous counterparts. It mainly relies on the super peroxidase-like activity of the designed noncovalent SNAzymes, promoted by a few nucleotides flanking on the 3'-terminals of common parallel G-quadruplexes (G4). For this reason, an unmodified G4 with an A5T30 head is well chosen and then attached robustly onto bare AuNPs via microwave-assisted heating-drying. A probe strand is meanwhile attached onto SNAzymes, enabling the target microRNA-triggered formation of a Y-shaped junction together with a capture strand tethered to a DNA tetrahedron on the electrode surface. The utilization of this tetrahedral nanoscaffold favors the ECL readout and thereby contributes to high sensitivity of the sensing platform. In this way, an AMI-related microRNA, miR-499, can be probed in a wide linear range, with a detection limit of 33 aM and high selectivity over other analogues. Furthermore, our developed sensing platform is employed to analyze endogenous miR-499 in AMI patients' blood, revealing an apparently higher level than the mean value of the healthy. What it means to patients, heart injury, is elucidated by comparing the miR-499 levels of cardiomyocytes and other tissue cells, with endogenous miR-16 as an intrinsic reference.

Acute Effects of Back Squat Combined with Different Elastic Band Resistance on Vertical Jump Performance in Collegiate Basketball Players.

The purpose of this study was to compare the acute effects of back squat exercise with or without elastic band on countermovement jump performance. Thirteen collegiate male basketball players (age: 20.5 ± 0.9 years; height: 188.5 ± 8.5 cm; body mass: 82.8 ± 12.9 kg) completed 5 familiarization and 4 experimental sessions separated by at least 48 hours. In the experimental sessions, the order of the conditions was randomized so that the participants performed 1 set of 3 repetitions of barbell back squat at 85% of their one-repetition maximum (1-RM), 1 set of 3 repetitions of back squat at 85% 1-RM with 20% variable resistance training (VRT), 30%VRT, or 40%VRT of the total load coming from the elastic band. Countermovement jump performance was assessed before (baseline), 30 seconds, 3 minutes, 6 minutes, and 9 minutes following each condition. Jump height, rate of force development, peak power, and vastus lateralis, vastus medialis, and medial gastrocnemius electromyography data were collected. Compared with the baseline, 30%VRT significantly improved jump height at 3 minutes post-exercise by 1.3 cm (P < 0.001) and 6 minutes post-exercise by 1.2 cm (P = 0.005); 40%VRT significantly improved jump height from 30 seconds up to the 9th minute (1.2 to 1.9 cm, P ≤ 0.036). The superior jump height was also accompanied by improved kinetic and electromyography data. No significant changes were observed in the barbell back squat and 20%VRT conditions. In conclusion, back squat at 85% 1-RM with 40% elastic band resistance led to superior vertical jump performance with an optimal time window of 3 minutes.

Association of energy-adjusted dietary inflammatory index and frailty in older adults with nonalcoholic fatty liver disease.

BACKGROUND: Energy-adjusted dietary inflammatory index (E-DII) can represent daily inflammatory dietary components and chronic inflammatory response is an important pathogenesis of aging, nonalcoholic fatty liver disease (NAFLD) and frailty. Therefore, the purpose of this study is to explore the association of E-DII and frailty in older adults with NAFLD. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2005-2016) to investigate the association between E-DII and frailty. The NAFLD status was determined using the US Fatty Liver Index (FLI) value ≥30. The relationship between E-DII and frailty was examined through multivariate weighted logistic regression analysis and smooth curve fitting. Subgroup analyses were conducted, considering various demographic and clinical variables. RESULTS: Our final analysis included 1586 individuals, with an average age of 69.42 years, and 53.15 % of them were males. The overall prevalence of frailty in the study population was 39.42 %. Smooth curve fitting analysis demonstrated a nearly linear relationship between E-DII and H. pylori. Utilizing multivariate weighted logistic regression analysis, we found that the odds ratio (OR) of E-DII for frailty was 1.08 (95%CI, 1.03-1.15). Subgroup analysis further confirmed that E-DII independently increased the risk of frailty. CONCLUSION: Higher E-DII levels were found to be associated with an increased risk of frailty in older adults with NAFLD. However, further studies are required to fully elucidate the precise mechanisms underlying the relationship between E-DII and frailty.

N-acetyltransferase 2 genetic polymorphisms and anti-tuberculosis-drug-induced liver injury: a correlation study.

Background: Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Conclusion: Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.

Neuroimaging anomalies in asymptomatic middle cerebral artery steno-occlusive disease with normal-appearing white matter.

Background: Asymptomatic chronic cerebrovascular steno-occlusive disease is common, but the cognitive function and alterations in the brain's structural and functional profiles have not been well studied. This study aimed to reveal whether and how patients with asymptomatic middle cerebral artery (MCA) steno-occlusive disease and normal-appearing white matter differ in brain structural and functional profiles from normal controls and their correlations with cognitive function. Methods: In all, 26 patients with asymptomatic MCA steno-occlusive disease and 22 healthy controls were compared for neurobehavioral assessments, brain volume, cortical thickness, fiber connectivity density (FiCD) value, and resting-state functional connectivity (FC) using multimodal MRI. We also investigated the associations between abnormal cortical thicknesses, FiCD values, and functional connectivities with the neurobehavioral assessments. Results: Patients performed worse on memory tasks (Auditory Verbal Learning Test-Huashan version) compared with healthy controls. Patients were divided into two groups: the right group (patients with right MCA steno-occlusive disease) and the left group (patients with left MCA steno-occlusive disease). The left group showed significant cortical thinning in the left superior parietal lobule, while the right group showed significant cortical thinning in the right superior parietal lobule and caudal portion of the right middle frontal gyrus. Increased FiCD values in the superior frontal region of the left hemisphere were observed in the left group. In addition, a set of interhemispheric and intrahemispheric FC showed a significant decrease or increase in both the left and right groups. Many functional connectivity profiles were positively correlated with cognitive scores. No correlation was found between cortical thickness, FiCD values, and cognitive scores. Conclusion: Even if the patients with MCA steno-occlusive disease were asymptomatic and had normal-appearing white matter, their cognitive function and structural and functional profiles had changed, especially the FC. Alterations in FC may be an important mechanism underlying the neurodegenerative process in patients with asymptomatic MCA steno-occlusive disease before structural changes occur, so FC assessment may promote the detection of network alterations, which may be used as a biomarker of disease progression and therapeutic efficacy evaluation in these patients.

Near-infrared active ferrocenyl porous organic polymer with photothermal enhanced enzymatic activity for combination antibacterial application.

As a severe ongoing global problem, bacterial contamination exists in every aspect of human life and the search for new antibacterial agents is urgently needed. Herein, a ferrocenyl porous organic polymer (FMC-POP) broad-spectrum antibacterial agent based on synergistic photothermal and peroxidase-like activity was prepared in a facile manner via the copolymerization of ferrocene diformaldehyde and cinnamaldehyde with mannitol through the acid-responsive acetal bond. The photoactive FMC-POP, with high photothermal conversion efficiency (41.45%), could convert not only the near-infrared laser irradiation into local heat to eradicate bacteria, but also low-concentration H2O2 into radical oxygen species (˙OH) that are effective against bacteria. Compared with single-mode photothermal (PTT) and enzymatic therapies, this combination therapy could significantly improve the bactericidal effect, exhibiting a germicidal efficiency of up to 99% (vs. 80.42% for PTT and 70% for enzyme). Thus, our work paves the way for a synergistic non-invasive antimicrobial therapy, which could expand the applications of POP-based artificial enzymes in biomedicine.

Manipulation of crystallization nucleation and thermal degradation of PLA films by multi-morphologies CNC-ZnO nanoparticles.

Currently, the quest for more renewable and biodegradable materials is a scientific priority to address the problems of petroleum-based plastics are difficult to degrade. In this work, cellulose nanocrystals (CNC) have been used as a template and four morphologies of CNC-ZnO nanocomposites were prepared via a hydrothermal method, and CNC-ZnO/polylactic acid (PLA) composite films were obtained by solution casting. We find that CNC-ZnO nanocomposites as heterogeneous nucleating agents improved the crystallinity and the film with flower-like CNC-ZnO was improved by 2.4 %. Ea required for thermal degradation of the PLA films decreased to 66-81 % of that of neat PLA, calculated by the Kissinger method, the Friedman method, and the Flynn-Wall-Ozawa (FWO) method. The R2 model was the solid degradation mechanism of the PLA films, analyzed through the Coats-Redfern method and the Criado method. The H-bond content of the composite films was significantly reduced after thermal aging at 150 °C. We found that three-dimensional CNC-ZnO (ZnO-3) made more prominent contributions to the crystallization, thermal degradation, and thermal aging of PLA films than other dimensional. The thermal properties can be regulated by the dimension, size, and apparent morphology of CNC-ZnO nanoparticles.

Diamond controls epithelial polarity through the dynactin-dynein complex.

Epithelial polarity is critical for proper functions of epithelial tissues, tumorigenesis, and metastasis. The evolutionarily conserved transmembrane protein Crumbs (Crb) is a key regulator of epithelial polarity. Both Crb protein and its transcripts are apically localized in epithelial cells. However, it remains not fully understood how they are targeted to the apical domain. Here, using Drosophila ovarian follicular epithelia as a model, we show that epithelial polarity is lost and Crb protein is absent in the apical domain in follicular cells (FCs) in the absence of Diamond (Dind). Interestingly, Dind is found to associate with different components of the dynactin-dynein complex through co-IP-MS analysis. Dind stabilizes dynactin and depletion of dynactin results in almost identical defects as those observed in dind-defective FCs. Finally, both Dind and dynactin are also required for the apical localization of crb transcripts in FCs. Thus our data illustrate that Dind functions through dynactin/dynein-mediated transport of both Crb protein and its transcripts to the apical domain to control epithelial apico-basal (A/B) polarity.

Clinical characteristics of pediatric hypertension: a multicenter study in China.

OBJECTIVES: Hypertension in children has attracted increasing attention. However, clinical-based studies investigating characteristics and secular trends of pediatric hypertension remain limited. This study aimed to investigate the clinical characteristics and secular trends of different types of hypertension among hospitalized children in China. METHODS: This retrospective analysis was based on medical records from nine tertiary children's hospitals in China during 2010∼2020. A total of 5847 pediatric inpatients (aged <18 years) with the diagnosis of hypertension were enrolled. Information on the clinical characteristics of each patient was obtained from their first admission records. RESULTS: During the past decade, secondary hypertension sustained to be the dominant type of hypertension in children, with the proportion increased from 51.2% during 2010∼2015 to 59.8% during 2016∼2020. The main causes of secondary hypertension were neurologic disorders in children aged 0∼2 years, which changed to renal diseases after 3 years of age. Compared with primary hypertension, secondary hypertension was common in girls (43.1 vs. 23.3%) and children under 5 years of age (32.2 vs. 2.1%). Moreover, over four-fifths of primary hypertensive individuals had obesity and obesity-related comorbidities, and the proportion of clusters of one or more comorbidities increased in the past decade (79.7 → 85.2%). CONCLUSION: Secondary hypertension sustained to be the dominant type of hypertension among children, especially in girls. Renal diseases were the most common causes of secondary hypertension in children, followed by rheumatic immune diseases. For primary hypertension, over four-fifths of inpatients had obesity and obesity-related diseases, and the proportion kept rising.

Structural Network Topology Reveals Higher Brain Resilience in Individuals with Preclinical Alzheimer's Disease.

Introduction: The diagnosis of Alzheimer's disease (AD) requires the presence of amyloid and tau pathology, but it remains unclear how they affect the structural network in the pre-clinical stage. We aimed to assess differences in topological properties in cognitively normal (CN) individuals with varying levels of amyloid and tau pathology, as well as their association with AD pathology burden. Methods: A total of 68 CN individuals were included and stratified by normal/abnormal (-/+) amyloid (A) and tau (T) status based on positron emission tomography results, yielding three groups: A-T- (n = 19), A+T- (n = 28), and A+T+ (n = 21). Topological properties were measured from structural connectivity. Group differences and correlations with A and T were evaluated. Results: Compared with the A-T- group, the A+T+ group exhibited changes in the structural network topology. At the global level, higher assortativity was shown in the A+T+ group and was correlated with greater tau burden (r = 0.29, p = 0.02), while no difference in global efficiency was found across the three groups. At the local level, the A+T+ group showed disrupted topological properties in the left hippocampus compared with the A-T- group, characterized by lower local efficiency (p < 0.01) and a lower clustering coefficient (p = 0.014). Conclusions: The increased linkage in the higher level architecture of the white matter network reflected by assortativity may indicate increased brain resilience in the early pathological state. Our results encourage further investigation of the topological properties of the structural network in pre-clinical AD.

Motor progression phenotypes in early-stage Parkinson's Disease: A clinical prediction model and the role of glymphatic system imaging biomarkers.

BACKGROUND: Substantial heterogeneity of motor symptoms in Parkinson's disease (PD) poses a challenge to disease prediction. OBJECTIVES: The aim of this study was to construct a nomogram model that can distinguish different longitudinal trajectories of motor symptom changes in early-stage PD patients. METHODS: Data on 90 patients with 5-years of follow-up were collected from the Parkinson's Progression Marker Initiative (PPMI) cohort. We used a latent class mixed modeling (LCMM) to identify distinct progression patterns of motor symptoms, and backward stepwise logistic regression with baseline information was conducted to identify the potential predictors for motor trajectory and to develop a nomogram. The performance of the nomogram model was then evaluated using the optimism-corrected C-index for internal validation, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for discrimination, the calibration curve for predictive accuracy, and decision curve analysis (DCA) for its clinical value. RESULTS: We identified two trajectories for motor progression patterns. The first, Class 1 (Motor deteriorated group), was characterized by sustained, continuously worsening motor symptoms, and the second, Class 2 (Motor stable group), had stable motor symptoms throughout the follow-up period. The best combination of 7 baseline variables was identified and assembled into the nomogram: Scopa-AUT [odds ratio (OR), 1.11; p = 0.091], Letter number sequencing (LNS) (OR, 0.76; p = 0.068), the asymmetry index of putamen (OR, 0.95; p = 0.034), mean caudate uptake (OR, 0.14; p = 0.086), CSF pTau/α-synuclein (OR, 0.00; p = 0.011), CSF tTau/Aß (OR, 25434806; p = 0.025), and the index for diffusion tensor image analysis along the perivascular space (ALPS-index) (OR, 0.02; p = 0.030). The nomogram achieved good discrimination, with an original AUC of 0.901 (95% CI, 0.813-0.989), and the bias-corrected concordance index (C-index) with 1,000 bootstraps was 0.834. The calibration curve and DCA also suggested both the high accuracy and clinical usefulness of the nomogram, respectively. CONCLUSIONS: This study proposes an effective nomogram to predict different motor progression patterns in early-stage PD. Furthermore, the imaging biomarker indicating glymphatic function could be an independent predictive factor for PD motor progression.

Regulatory roles of Osteopontin in lung epithelial inflammation and epithelial-telocyte interaction.

BACKGROUND: Lung epithelial cells play important roles in lung inflammation and injury, although mechanisms remain unclear. Osteopontin (OPN) has essential roles in epithelial damage and repair and in lung cancer biological behaviours. Telocyte (TC) is a type of interstitial cell that interacts with epithelial cells to alleviate acute inflammation and lung injury. The present studies aim at exploring potential mechanisms by which OPN regulates the epithelial origin lung inflammation and the interaction of epithelial cells with TCs in acute and chronic lung injury. METHODS: The lung disease specificity of OPN and epithelial inflammation were defined by bioinformatics. We evaluated the regulatory roles of OPN in OPN-knockdown or over-expressed bronchial epithelia (HBEs) challenged with cigarette smoke extracts (CSE) or in animals with genome OPN knockout (gKO) or lung conditional OPN knockout (cKO). Acute lung injury and chronic obstructive pulmonary disease (COPD) were induced by smoking or lipopolysaccharide (LPS). Effects of OPN on PI3K subunits and ERK were assessed using the inhibitors. Spatialization and distribution of OPN, OPN-positive epithelial subtypes, and TCs were defined by spatial transcriptomics. The interaction between HBEs and TCs was assayed by the co-culture system. RESULTS: Levels of OPN expression increased in smokers, smokers with COPD, and smokers with COPD and lung cancer, as compared with healthy nonsmokers. LPS and/or CSE induced over-production of cytokines from HBEs, dependent upon the dysfunction of OPN. The severity of lung inflammation and injury was significantly lower in OPN-gKO or OPN-cKO mice. HBEs transferred with OPN enhanced the expression of phosphoinositide 3-kinase (PI3K)CA/p110α, PIK3CB/p110ß, PIK3CD/p110δ, PIK3CG/p110γ, PIK3R1, PIK3R2 or PIK3R3. Spatial locations of OPN and OPN-positive epithelial subtypes showed the tight contact of airway epithelia and TCs. Epithelial OPN regulated the epithelial communication with TCs, and the down-regulation of OPN induced more alterations in transcriptomic profiles than the up-regulation. CONCLUSION: Our data evidenced that OPN regulated lung epithelial inflammation, injury, and cell communication between epithelium and TCs in acute and chronic lung injury. The conditional control of lung epithelial OPN may be an alternative for preventing and treating epithelial-origin lung inflammation and injury.

The effects of trunk kinematics and EMG activity of wheelchair racing T54 athletes on wheelchair propulsion speeds.

Background: The purpose of this study is to examine the impact of trunk kinematic characteristics and trunk muscle electromyography (EMG) activity on propulsion speeds in wheelchair racing T54 athletes. Method: The Vicon infrared high-speed 3D motion capture system was utilized to acquire kinematic data of the shoulders, elbows, wrists, and trunk from twelve T54 athletes at four different speeds (5.55 m/s, 6.94 m/s, 8.33 m/s, and personal maximum speed). Additionally, the Trigno Wireless EMG system was employed to collect synchronous surface electromyography (EMG) data from the rectus abdominis and erector spinae muscles. The kinematics and EMG data of the trunk were compared across various wheelchair propulsion speeds while also examining the correlation coefficient between wheelchair propulsion speeds and: (1) the range of motion of upper limb joints as well as the trunk; (2) the maximum angular velocities of the upper limbs joints as well as the trunk; and (3) rectus abdominis and erector spinae EMG activity. Two multiple linear stepwise regression models were utilized to examine the impact of variables that had been identified as significant through correlation coefficient tests (1) and (2) on propulsion speed, respectively. Results: There were significant differences in the range of motion (p<0.01) and angular velocity (p<0.01) of the athlete's trunk between different propulsion speeds. The range of motion (p<0.01, r = 0.725) and angular speed (p<0.01, r = 0.882) of the trunk showed a stronger correlation with propulsion speed than did upper limb joint movements. The multiple linear stepwise regression model revealed that the standardized ß values of trunk motion range and angular velocity in athletes were greater than those of other independent variables in both models. In terms of the EMG variables, four of six variables from the rectus abdominis showed differences at different speeds (p<0.01), one of six variables from the erector spinae showed differences at different speeds (p<0.01). All six variables derived from the rectus abdominis exhibited a significant correlation with propulsion speed (p<0.05, r>0.3), while one variable derived from the erector spinae was found to be significantly correlated with propulsion speed (p<0.01, r = 0.551). Conclusion: The movement of the trunk plays a pivotal role in determining the propulsion speed of wheelchair racing T54 athletes. Athletes are advised to utilize trunk movements to enhance their wheelchair's propulsion speed while also being mindful of the potential negative impact on sports performance resulting from excessive trunk elevation. The findings of this study indicate that it would be beneficial for wheelchair racing T54 athletes to incorporate trunk strength training into their overall strength training regimen, with a specific emphasis on enhancing the flexion and extension muscles of the trunk.

Association of Dietary Inflammation Index and Helicobacter pylori Immunoglobulin G Seropositivity in US Adults: A Population-Based Study.

Background: Dietary patterns play important role in Helicobacter pylori (H. pylori) infection. We aimed to investigate the potential relationship between Dietary Inflammation Index (DII) and H. pylori infection in US adults. Methods: This cross-sectional study was based on National Health and Nutrition Examination Survey (1999-2000). Individuals aged ≥20 years who provided a 24 hr dietary intake history and underwent H. pylori testing were included in the analysis. Multivariate weighted logistic regression analysis, smooth curve fitting, and subgroup analysis were used to investigate the relationship between DII and H. pylori infection. Subgroup analyses were based on demographic and clinical variables. Results: There were 4,000 individuals enrolled in our final analysis. The overall mean age was 45.92 years and 46.77% were males. The overall prevalence of H. pylori infection in the study population was 45.9%. The smooth curve fitting analysis indicated a near-linear relationship between DII and H. pylori. In multivariate weighted logistic regression analysis, the odds ratio (OR) of DII is 1.17 (95% confidence interval (CI), 1.09-1.27) for H. pylori infection. In subgroup analysis, DII still increased the risk of H. pylori infection independently. Conclusions: The increased DII levels were associated with an increased risk of H. pylori infection among US adults. Further studies are needed to elucidate the exact mechanisms of DII and H. pylori infection.