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Rheumatoid arthritis (RA) is a chronic inflammatory disease which is closely related to genetic background. Single‐nucleotide polymorphisms (SNPs) have been found to play an important role in the development of RA. This study intends to investigate the links between gene polymorphisms in the interleukin‐23 receptor (IL23R) and interleukin 17A (IL17A) and susceptibility to RA in the Western Chinese Han population. Four SNPs (rs6693831 T > C, rs1884444 G > T, and rs7517847 T > G in IL23R gene, and rs2275913 G > A in IL17A gene) were genotyped in 246 RA patients and 362 healthy controls by high resolution melting analysis. The comparative analyses among genotype distributions, clinical indicators, and IL‐17A and IL‐23R levels in RA patients were also performed. The study revealed that the SNP rs6693831 and rs1884444 of IL23R had a significant association with RA susceptibility. The frequencies of rs6693831 genotype CC and allele C were significantly higher in the RA group and associated with higher RA risk compared with genotype TT and allele T (OR = 7.797, 95% confidence interval [CI] = 4.072–14.932 and OR = 5.984, 95%CI = 3.190–11.224, respectively). The TT genotype of rs1884444 appeared to decrease the RA risk compared with the GG genotype (OR =.251, 95%CI =.118–.536). The genotype CC and allele C of rs6693831 and the genotype GG and allele G of rs1884444 may be risk factors for RA. IL23R gene polymorphisms may be involved in the risk of RA susceptibility in the Western Chinese Han population. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) plays a significant role as an epigenetic mechanism, which is involved in various cancers' progress via regulating mRNA modification. As a crucial m6A "reader", YTHDF1 is able to alter m6A-modified mRNA and promote the protein translation process in multiple cancers. However, the role of YTHDF1 in lung cancer has not been fully investigated. This study focuses on elucidating the function of YTHDF1 in the development of lung cancer and its underlying mechanism. We demonstrated that YTHDF1 was highly expressed in lung carcinoma progression; then, the loss of function experiments in lung cell lines confirmed that knockdown of YTHDF1 suppressed cell proliferation, migration and invasion and induced ferroptosis of lung cancer cells. Further functional assays showed that ferritin (FTH) was identified as the key target of YTHDF1 in lung cancer cells. Furthermore, the overexpression of ferritin in YTHDF1-depleted cells partially restored lung cancer cell suppression. Collectively, our data suggested that the upregulation of YTHDF1 promotes lung cancer carcinogenesis by accelerating ferritin translation in an m6A-dependent manner. We hope that our findings may provide a new target for lung cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: The process of aging and metabolism are intricately linked, thus rendering the identification of reliable biomarkers related to metabolism crucial for delaying the aging process. However, research of reliable markers that reflect aging profiles based on machine learning is scarce. Methods: Serum samples were obtained from aged mice (18-month-old) and young mice (3-month-old). LC-MS was used to perform a comprehensive analysis of the serum metabolome and machine learning was used to screen potential aging-related biomarkers. Results: In total, aging mice were characterized by 54 different metabolites when compared to control mice with criteria: VIP ≥ 1, q-value < 0.05, and Fold-Change ≥ 1.2 or ≤0.83. These metabolites were mostly involved in fatty acid biosynthesis, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, and the citrate cycle (TCA cycle). We merged the comprehensive analysis and four algorithms (LR, GNB, SVM, and RF) to screen aging-related biomarkers, leading to the recognition of oleic acid. In addition, five metabolites were identified as novel aging-related indicators, including oleic acid, citric acid, D-glutamine, trypophol, and L-methionine. Conclusions: Changes in the metabolism of fatty acids and conjugates, organic acids, and amino acids were identified as metabolic dysregulation related to aging. This study revealed the metabolic profile of aging and provided insights into novel potential therapeutic targets for delaying the effects of aging. [ABSTRACT FROM AUTHOR]

Background: To investigate the prevalence and risk factors of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM) in a suburb (Qingpu) of Shanghai, China. Methods: A population-based cross-sectional study. A total of 7462 residents with T2DM in Qingpu were enrolled according to the resident health archives from January 2020 to December 2020. Blood and urine samples of the subjects were collected. Disc- and macula-centred retinal images were taken to assess DR. SPSS was used to analyse and investigate the prevalence and risk factors of DR. Results: The fundus images of 6380 (85.5%) subjects were of sufficiently good quality for grading. The average (range) age of 6380 subjects was 63.46±7.77 (28–92) years. Six hundred forty-four subjects were diagnosed with DR. The prevalence of DR was 10.1% (95% CI 9.4%-10.8%), with mild, moderate, and severe non-proliferative retinopathy and proliferative retinopathy being 2.1%, 6.3%, 1.3% and 0.4%, respectively. The prevalence of bilateral DR was 6.5%. Higher T2DM duration (OR, 1.057), fasting plasma glucose (OR, 1.063), glycated hemoglobinA1c (OR, 1.269), urea nitrogen (OR, 1.059), and urinary albumin (OR, 1.001) were associated with the higher DR prevalence. Conclusion: The prevalence of DR among Chinese adults with T2DM in Qingpu was 10.1%, in which non-proliferative DR was more common. Higher fasting plasma glucose and glycated hemoglobinA1c are well-known risk factors of DR, consistent with the findings in our study. Our study didn't find the risk between lipid indicators and DR. However, several renal function indicators, like higher urea nitrogen and urinary albumin, were risk factors for DR in this study. Appropriate diagnosis and intervention should be taken in time to prevent and control DR development. [ABSTRACT FROM AUTHOR]

Introduction. Acetaminophen is a common medication involved in deliberate and accidental self-poisoning. The acetaminophen treatment nomogram is used to guide acetylcysteine treatment. It is rare to develop hepatotoxicity with an initial acetaminophen concentration below the nomogram line. We present a case of acetaminophen ingestion with an initial concentration below the nomogram line that developed hepatic failure, due to a delayed peak acetaminophen concentration secondary to coingesting medications that slow gastric emptying. Case Report. A 43-year-old (55 kg) female presented after ingesting an unknown quantity of acetaminophen, clonidine, and alcohol. Her acetaminophen level was 41 mg/L (256 μmol/L) at 4.5 h post-ingestion, well below the nomogram line, and ALT was 25 U/L. Hence, acetylcysteine was not commenced. She was intubated for decreased level of conscious. A repeat acetaminophen level 4 h later was 39 mg/L (242 μmol/L), still below the nomogram line. She was extubated 24 h later.At 38 h post-ingestion she developed abdominal pain, the repeat acetaminophen level was 85 mg/L (560 μmol/L), ALT was 489 U/L, and acetylcysteine was commenced. The patient developed hepatic failure with a peak ALT of 7009 U/L and INR of 7.5 but made a full recovery. It was discovered that she had ingested a combination acetaminophen product containing dextromethorphan and chlorphenamine. Acetaminophen metabolites were measured, including nontoxic glucuronide and sulfate conjugates and toxic cytochrome P450 (CYP) metabolites. The metabolite data demonstrated increasing CYP metabolites in occurrence with the delayed acetaminophen peak concentration. Discussion. Opioids and antimuscarinic agents are known to delay gastric emptying and clonidine may also have contributed. These coingested medications resulted in delayed acetaminophen absorption. This case highlights the issue of altered pharmacokinetics when patients coingest gut slowing agents. [ABSTRACT FROM AUTHOR]

• The rs73620203 locus is correlated with RA susceptibility, and the genotypes carrying the T allele are protective factors of RA. The same findings were illustrated in female RA patients. • Among the three genotypes CC, CT, and TT of rs73620203, serum osteocalcin and BALP levels were significantly lower in the TT genotype than in the CC and CT genotypes, while serum β-CTX levels were not significantly different. • It is inferred that T allele at rs73620203 in TGIF gene may be related to the role of the rs73620203 locus in regulating the TGIF gene expression and thus regulating the function of the Smad signaling pathway. • It is suggested that TGIF gene polymorphisms perhaps can be regarded as novel markers for predicting the risk of developing RA. To explore the association of single nucleotide polymorphisms (SNPs) in the transforming growth interacting factor (TGIF) gene with bone metabolism markers and rheumatoid arthritis (RA) susceptibility. Three SNPs were genotyped in 155 RA patients and 168 healthy controls using high-resolution melting (HRM) analysis. The serum levels of osteocalcin, bone alkaline phosphatase (BALP), and β type I collagen-crosslinked C telopeptide (β-CTX) were detected using electrochemical luminescence in 108 patients randomly selected from the RA group. Genotype and allele frequency analysis showed that rs73620203 was associated with bone erosion in RA (P = 0.012 and P = 0.003, respectively), and individuals carrying the T allele for rs73620203 showed a decreased RA risk (OR = 0.59, 95% CI = 0.42–0.84; P = 0.003). In sex-specific analysis, the rs73620203 polymorphism was associated with susceptibility to RA in women (P = 0.022 and P = 0.006, respectively). In addition, RA patients with three genotypes at the rs73620203 locus showed significant differences in serum osteocalcin and BALP (P = 0.006 and P = 0.037, respectively). Haplotype analysis revealed that the haploid ATG and GCA frequencies were significantly lower in the RA group (P = 0.036, OR = 0.693; P = 0.002, OR = 0.189, respectively), while the haploid ACA frequency of the RA group was enhanced (P < 0.01, OR = 5.058). Our study provides the first evidence that rs73620203 is associated with RA susceptibility and the relationship between TGIF gene SNPs and the regulation of bone metabolism in RA patients. [ABSTRACT FROM AUTHOR]

Guest-induced reversible crystal-to-amorphous-to-crystal transformation was obtained in a Co(ii)-based metal–organic framework (MOF), DPPB-1, accompanied by a colour change. In this study, amorphous samples (DPPB-2) exhibited a notably high adsorption capacity for methanol (8.25 mmol g−1) and ethanol (7.99 mmol g−1). These samples also showed a high adsorption selectivity for methanol or ethanol over volatile organic compounds, which was further confirmed by density functional theory (DFT) calculations and non-covalent interaction (NCI) analysis. Such unique properties endowed DPPB-1 with a promising potential for applications in the field of methanol/ethanol separation and sensing materials. [ABSTRACT FROM AUTHOR]

The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN) in patients with deep brain stimulation (DBS) electrodes. We found that STN LFP activities in the gamma (55-90 Hz) and beta (13-30m Hz) bands were most informative about gripping force, and that a first order dynamic linear model with these STN LFP features as inputs can be used to decode the temporal profile of gripping force. Our results enhance the understanding of how the basal ganglia control gripping force, and also suggest that deep brain LFPs could potentially be used to decode movement parameters related to force and movement vigour for the development of advanced human-machine interfaces. [ABSTRACT FROM AUTHOR]

Voluntary movements are followed by a post-movement electroencephalography ( EEG) beta rebound, which increases with practice and confidence in a task. We hypothesized that greater beta modulation reflects less load on cognitive resources and may thus be associated with faster reactions to new stimuli. EEG was recorded in 17 healthy subjects during rhythmically paced index finger tapping. In a STOP condition, participants had to interrupt the upcoming tap in response to an auditory cue, which was timed such that stopping was successful only in ~ 50% of all trials. In a second condition, participants carried on tapping twice after the stop signal ( CONTINUE condition). Thus the conditions were distinct in whether abrupt stopping was required as a second task. Modulation of 12-20 Hz power over motor and parietal areas developed with time on each trial and more so in the CONTINUE condition. Reduced modulation in the STOP condition went along with reduced negative mean asynchronies suggesting less confident anticipation of the timing of the next tap. Yet participants were more likely to stop when beta modulation prior to the stop cue was more pronounced. In the STOP condition, expectancy of the stop signal may have increased cognitive load during movement execution given that the task might have to be stopped abruptly. However, within this condition, stopping ability was increased if the preceding tap was followed by a relatively larger beta increase. Significant, albeit weak, correlations confirmed that increased post-movement beta power was associated with faster reactions to new stimuli, consistent with reduced cognitive load. [ABSTRACT FROM AUTHOR]

The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4–8 Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC–STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. [ABSTRACT FROM AUTHOR]

Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. [ABSTRACT FROM AUTHOR]

Monitoring and evaluating movement errors to guide subsequent movements is a critical feature of normal motor control. Previously, we showed that the postmovement increase in electroencephalographic (EEG) beta power over the sensorimotor cortex reflects neural processes that evaluate motor errors consistent with Bayesian inference (Tan et al., 2014). Whether such neural processes are limited to this cortical region or involve the basal ganglia is unclear. Here, we recorded EEG over the cortex and local field potential (LFP) activity in the subthalamic nucleus (STN) from electrodes implanted in patients with Parkinson's disease, while they moved a joystick-controlled cursor to visual targets displayed on a computer screen. After movement offsets, we found increased beta activity in both local STN LFP and sensorimotor cortical EEG and in the coupling between the two, which was affected by both error magnitude and its contextual saliency. The postmovement increase in the coupling between STN and cortex was dominated by information flow from sensorimotor cortex to STN. However, an information drive appeared from STN to sensorimotor cortex in the first phase of the adaptation, when a constant rotation was applied between joystick inputs and cursor outputs. The strength of the STN to cortex drive correlated with the degree of adaption achieved across subjects. These results suggest that oscillatory activity in the beta band may dynamically couple the sensorimotor cortex and basal ganglia after movements. In particular, beta activity driven from the STN to cortex indicates task-relevant movement errors, information that may be important in modifying subsequent motor responses. [ABSTRACT FROM AUTHOR]

Parkinson’s disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson’s disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = −4.4, p<0.001). There was significant coherence between the two sides in the beta range in 19 of the subjects. Coherence was selectively attenuated in the low beta range following levodopa (t22 = −2.7; p = 0.01). We also separately analysed amplitude co-modulation and phase synchronisation in the beta band and found significant amplitude co-modulation and phase locking values in 17 and 16 subjects respectively, off medication. There was a dissociable effect of levodopa on these measures, with a significant suppression only in low beta phase locking value (t22 = −2.8, p = 0.01) and not amplitude co-modulation. The absolute mean values of amplitude co-modulation (0.40±0.03) and phase synchronisation (0.29±0.02) off medication were, however, relatively low, suggesting that the two basal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei. [ABSTRACT FROM AUTHOR]

Abstract: The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. Here we investigated the relationship between frequency-specific oscillatory activities in the subthalamic nucleus (STN) and manual grips made with different efforts. The latter were self-rated using the 10 level Borg scale ranging from 0 (no effort) to 10 (maximal effort). STN LFP activities were recorded in patients with Parkinson's Disease (PD) who had undergone functional surgery. Patients were studied while motor performance was improved by dopaminergic medication. In line with previous studies we observed power increase in the theta/alpha band (4–12Hz), power suppression in the beta band (13–30Hz) and power increase in the gamma band (55–90Hz) and high frequency band (101–375Hz) during voluntary grips. Beta suppression deepened, and then reached a floor level as effort increased. Conversely, gamma and high frequency power increases were enhanced during grips made with greater effort. Multiple regression models incorporating the four different spectral changes confirmed that the modulation of power in the beta band was the only independent predictor of effort during grips made with efforts rated <5. In contrast, increases in gamma band activity were the only independent predictor of effort during grips made with efforts ≥5. Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function is thought to be impaired in untreated PD where task-related reactivity in these two bands is deficient. [Copyright &y& Elsevier]

Abstract: Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson''s disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5–12Hz (in the theta/alpha band) independently predicted better performance—reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55–375Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13–23Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5–12Hz and 55–375Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13–25Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip. [Copyright &y& Elsevier]

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson’s disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson’s disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5–12 Hz) and high-gamma/high-frequency (55–375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (&leq;13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual’s peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli. [ABSTRACT FROM AUTHOR]

Background. Fu Fang Zhen Zhu Tiao Zhi (FTZ) is a traditional Chinese herbal prescription widely used to treat dyslipidemia, metabolic diseases, and diabetic coronary disorders. Cardiomyocyte death and loss of regenerative ability cause cardiac dysfunction and heart failure. FTZ can effectively treat diabetic cardiomyopathy and macrovascular diseases; however, the mechanism behind the phenomenon is still unclear. Here, we determined the mechanism of action of FTZ in treating myocardial infarction. Methods. Male C57BL/6 mice were treated with 2.4 or 1.2 g/kg FTZ, or administered saline by oral gavage daily for four weeks, and a 24-hour ligation was administered to the artery. Echocardiography was used to evaluate cardiac function. Hematoxylin and eosin and Evans blue/triphenyltetrazolium chloride staining were carried out by staining the cardiac tissue, used to evaluate cardiac function and infarct size. Using western blotting and reverse transcriptase-polymerase chain reaction, we determined the relative levels of NOD-like receptor protein (NLRP) 3, ASC, cleaved caspase-l (C-Caspase-1), GSDMD, and GSDMD-N. TUNEL, immunohistochemical, and immunofluorescence staining were used to determine cell death and NLRP3 expression. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-1β and IL-18. Results. FTZ reduced ischemia-induced cardiomyocyte cell death in vivo and H2O2-induced cell death in vitro by maintaining cardiac architecture and restoring cardiac function. FTZ decreased the NLRP3 expression and inhibited pyroptosis-correlated genes, including NLRP3, ASC, GSDMD, C-Caspase-1, and GSDMD-N. NLRP3 overexpression impaired the efficacy of FTZ by inducing pyroptosis. Conclusion. FTZ could preserve cardiac function resulting from ischemic insult by inhibiting pyroptosis, which was partially reversed by NLRP3 overexpression, indicating that NLRP3 could be a potential target of FTZ in treating myocardial infarction. [ABSTRACT FROM AUTHOR]

Summary: The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren''s syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. [ABSTRACT FROM AUTHOR]

Manoeuverability is a key requirement for successful terrestrial locomotion, especially on variable terrain, and is a deciding factor in predator-prey interaction. Compared with straight-line running, bend running requires additional leg force to generate centripetal acceleration. In humans, this results in a reduction in maximum speed during bend running and a published model assuming maximum limb force as a constraint accurately predicts how much a sprinter must slow down on a bend given his maximum straight-line speed. In contrast, greyhounds do not slow down or change stride parameters during bend running, which suggests that their limbs can apply the additional force for this manoeuvre. We collected horizontal speed and angular velocity of heading of horses while they turned in different scenarios during competitive polo and horse racing. The data were used to evaluate the limits of turning performance. During high-speed turns of large radius horizontal speed was lower on the bend, as would be predicted from a model assuming a limb force limit to running speed. During small radius turns the angular velocity of heading decreased with increasing speed in a manner consistent with the coefficient of friction of the hoof-surface interaction setting the limit to centripetal force to avoid slipping. [ABSTRACT FROM AUTHOR]

Patients with Parkinson's disease can show brief but dramatic normalization of motor activity in highly arousing situations, a phenomenon often termed paradoxical kinesis. We sought to mimic this in a controlled experimental environment. Nine patients with Parkinson's disease and nine age‐matched healthy controls were asked to grip a force dynamometer as quickly and strongly as possible in response to a visual cue. A loud (96 dB) auditory stimulus was delivered at the same time as the visual cue in ∼50% of randomly selected trials. In patients with Parkinson's disease, the experiment was conducted after overnight withdrawal of antiparkinsonian drugs and again 1 h after patients had taken their usual morning medication. Patients showed improvements in the peak rate of force development and the magnitude of force developed when loud auditory stimuli accompanied visual cues. Equally, they showed improvements in the times taken to reach the peak rate of force development and their maximal force. The paradoxical facilitatory effect of sound was similar whether patients were off or on their usual antiparkinsonian medication, and could be reproduced in age‐matched healthy controls. We conclude that motor improvement induced by loud auditory stimuli in Parkinson's disease is related to a physiological phenomenon which survives both with and after withdrawal of antiparkinsonian medication. The potential independence of the mediating pathways from the dopaminergic system provides impetus for further investigation as it may yield a novel nondopaminergic target for therapeutic manipulation in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Could task performance be constrained by our ability to fully engage necessary neural processing through effort of will? The StartReact phenomenon suggests that this might be the case, as voluntary reaction times are substantially reduced by loud sounds. Here, we show that loud auditory stimulation can also be associated with an improvement in the force and speed of force development when 18 healthy subjects are repeatedly asked to make a maximal grip as fast and as strongly as possible. Peak grip force was increased by 7.2 ± 1.4% (SEM) ( P < 0.0001), and the rate of force development was increased by 17.6 ± 2.0% ( P ≪ 0.00001), when imperative visual cues were accompanied by a loud auditory stimulus rather than delivered alone. This implies that loud auditory stimuli may allow motor pathways to be optimised beyond what can be achieved by effort of will alone. [ABSTRACT FROM AUTHOR]

Abstract: Consistent measurement of maximum running speed overground is problematic due to the difficulty in precise, continual measurement of speed, and the substantial workload in accelerating the body promoting the onset of fatigue. Treadmills remove the requirement for acceleration which enables more repeats. They also allow experiments to be carried out in controlled environments and where space is limited, but they usually depend on manual and subjective speed control. Here we used a draw-wire position sensor and a proportional–derivative (PD) controller to automatically adjust treadmill belt speed of a large equine treadmill. The feedback loop took the real-time position and velocity of the runner relative to the front of the treadmill as input. This control system allowed runners to accelerate from walking speed to a peak running speed within a few strides and then decelerate as quickly as they wished. We used the system to evaluate the variation in maximum speed determination that results from one trial to 10 trials, in eleven individuals. Three trials gave a maximum speed 97.8% of that achieved after ten. The approach used is appropriate for any treadmill where the running zone length is greater than three metres and the speed controller can be externally controlled. Subjects ran 11.5% faster on the treadmill than overground, part of which can be explained by the removal of aerodynamic drag and the fatigue of overground running. Additional factors may, however, contribute to athletes running faster on a treadmill, for instance some aspect of stability or control. [Copyright &y& Elsevier]

Abstract: Both GPS and inertial measurement units (IMUs) have been extensively used in biomechanical studies. Expensive high accuracy GPS units can provide information about intrastride speed and position, but their application is limited by their size and cost. Single and double integration of acceleration from IMU provides information about short-term fluctuations in speed and position, but suffers from integration error over a longer period of time. The integration of GPS and IMU has been widely used in large and expensive units designed for survey and vehicle navigation. Here we propose a data fusion scheme, which is a Kalman filter based complementary filter and enhances the frequency response of the GPS and IMU used alone. We also report the design of a small (28g) low cost GPS/IMU unit. Its accuracy after post-processing with the proposed data fusion scheme for determining average speed and intrastride variation was compared to a traditional high cost survey GPS. The low cost unit achieved an accuracy of 0.15ms−1 (s.d.) for horizontal speed in cycling and human running across a speed range of 3–10ms−1. The stride frequency and vertical displacement calculated based on measurements from the low cost GPS/IMU units had an s.d. of 0.08Hz and 0.02m respectively, compared to measurements from high performance OEM4 GPS units. [Copyright &y& Elsevier]

Background: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. Objective: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. Methods: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). Results: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian‐parafascicular complex (CM‐pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 μs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow‐up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. Conclusion: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population. [ABSTRACT FROM AUTHOR]

Economic security is a core theoretical issue in economics. In modern economic conditions, the ups and downs caused by economic instability in any economic system will affect the stability of the financial market, bring huge losses to the economy, and affect the development of the whole national economy. Therefore, research on the regularity of economic security and economic fluctuations is one of the important contents to ensure economic stability and scientific development. Accurate monitoring and forecasting of economic security are an indispensable link in economic system regulation, and it is also an important reference factor for any economic organization to make decisions. This article focuses on the construction of an economic security early warning system as the main research content. It integrates cloud computing and data mining technologies and is supported by CNN-SVM algorithm and designs an early warning model that can adaptively evaluate and warn the economic security state. Experiments show that when the CNN network in the model uses ReLU activation function and SVM uses RBF function, the prediction accuracy can reach 0.98, and the prediction effect is the best. The data set is verified, and the output Q province's 2018 economic security early warning comprehensive index is 0.893. The 2019 economic security early warning index is 0.829, which is consistent with the actual situation. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous vagus nerve stimulation (VNS) showed early evidence of efficacy for the gait treatment of Parkinson's disease (PD). Objectives: Providing data on neurophysiological and clinical effects of transauricular VNS (taVNS). Methods: Ten patients with recording deep brain stimulation (DBS) have been enrolled in a within participant design pilot study, double‐blind crossover sham‐controlled trial of taVNS. Subthalamic local field potentials (β band power), Unified Parkinson's Disease Rating Scales (UPDRS), and a digital timed‐up‐and‐go test (TUG) were measured and compared with real versus sham taVNS during medication‐off/DBS‐OFF condition. Results: The left taVNS induced a reduction of the total β power in the contralateral (ie, right) subthalamic nucleus and an improvement of TUG time, speed, and variability. The taVNS‐induced β reduction correlated with the improvement of gait speed. No major clinical changes were observed at UPDRS. Conclusions: taVNS is a promising strategy for the management of PD gait, deserving prospective trials of chronic neuromodulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Fufang Zhenzhu TiaoZhi (FTZ), a Chinese medicinal decoction, has continuously been used to treat metabolic syndrome. Atherosclerosis is the main pathological basis of cardiovascular disease. The N6 methyladenosine (m6A) modification is a highly dynamic and reversible process involving a variety of important biological processes. Here, we investigated the therapeutic effects and mechanism of FTZ in diabetes-accelerated atherosclerosis. Doppler ultrasonography was used to examine the carotid intima-media thickness and plaque area in diabetic atherosclerosis patients. HFD mice were injected with streptozotocin to induce diabetes. HE and Oil red O staining were used to assess the effect of FTZ on lipid deposition. HUVECs were induced with HG/ox-LDL as a model of diabetic atherosclerosis. Furthermore, application of m6A methylation level kit, qRT-PCR, Western blot, tunel staining, reactive oxygen species staining and mPTP staining were performed to analyze the detailed mechanism. Clinical trials of FTZ have shown obvious effect of lowering blood glucose and blood lipids. These effects were reversed after FTZ intervention. Compared with the control, lipid deposition decreased significantly after FTZ administration. FTZ reduced endothelial cell apoptosis. At the same time, we found that FTZ reversed the increase of methylation reader YTHDF2 caused by ox-LDL treatment. Subsequently, we discovered that YTHDF2 degraded SIRT3 mRNA, leading to endothelial cell apoptosis and oxidative stress. FTZ attenuated diabetes-accelerated atherosclerosis by decreasing blood glucose and serum lipids levels, and increased endothelial cell antioxidant capacity, inhibited endothelial cell apoptosis via inhibiting YTHDF2-mediated m6A modification of SIRT3 mRNA, which reduced mRNA degradation. [Display omitted] • FTZ plays a significant inhibitory role in diabetes-accelerated atherosclerosis via YTHDF2-dependent m6A manner. • FTZ mediates m6A modification via regulating YTHDF2. • SIRT3 is one of the underlying targets for the therapeutic effect of FTZ on diabetes-accelerated atherosclerosis. [ABSTRACT FROM AUTHOR]

Although the educational potential of social media has been widely acknowledged, it remains unclear whether social media use might present opportunities for the development of math identity. This study drew on the socialization framework of math identity to examine the relationships between social media use for math learning, bicultural identity integration, ethnic‐math beliefs and math identity among ethnic minority high school students in China. Structural equation modelling results showed that (a) social media use was positively related to math identity; (b) high bicultural identity integration was positively associated with math identity, while biased ethnic‐math beliefs were negatively related to math identity and (c) social media use suppressed the socialization process of math identity, weakening the maladaptive roles of low bicultural identity integration and biased ethnic‐math beliefs in shaping math identity. Our findings highlight the beneficial role of social media use in student math learning. Theoretical and practical implications are discussed. Practitioner notesWhat is already known about this topicSocial media use for learning is associated with students' academic motivation, engagement and academic achievement.Social media use may have affordances for identity development, especially for ethnic minorities.The formation of ethnic minority students' math identity is intertwined with their math and ethnic socialization.What this paper addsSocial media use for math learning was directly and positively related to ethnic minorities' math identity.This study quantitatively confirmed the associations of bicultural identity integration and ethnic‐math beliefs with math identity.Social media use suppressed the relations of bicultural identity integration and ethnic‐math beliefs with math identity.Implications for practice and/or policyPromoting social media use for math learning benefits ethnic minority students' math identity.Social media use for math learning could alleviate the maladaptive role of low bicultural identity integration and biased ethnic‐math beliefs in math identity development.Ethnic minority students' math identity socialization processes merit attention. [ABSTRACT FROM AUTHOR]

After irradiation, double-stranded DNA leaked into the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to the production of type I interferon (IFNI). In this study, we sought to probe the effect of ionizing radiation on activity of cGAS-STING-IFNI pathway in normoxic or hypoxic glioma cells and explore a more effective method to activate the signaling pathway, thereby activating the anti-tumor immune response and improving the therapeutic effect of radiotherapy for glioma. Human glioma cells U251 and T98G cultured in normoxia or hypoxia (1% O2) were irradiated with different doses of X-ray. The relative expressions of cGAS, IFN-I stimulated genes (ISGs), and three-prime repair exonuclease 1 (TREX1) were detected by qPCR. The expression levels of interferon regulatory factor 3 (IRF3) and p-IRF3 proteins were detected by Western blot. The production of cGAMP and IFN-β in the supernatant was detected by ELISA assay. U251 and T98G cell lines with stable knockdown of TREX1 were established after transfection with lentivirus vectors. EdU cell proliferation assay was used to screen suitable metal ions concentrations. The phagocytosis of DCs was observed by immunofluorescence microscope. The phenotype of DCs was detected by flow cytometry. The migration ability of DCs was detected by a transwell experiment. We found that cytosolic dsDNA, 2′3′-cGAMP, cGAS and ISGs expression, and IFN-β in cell supernatant were all increased with the doses of X-ray in the range of 0–16 Gy in normoxic glioma cells. Nevertheless, hypoxia significantly inhibited the radiation-induced dose-dependent activation of cGAS-STING-IFNI pathway. Furthermore, manganese (II) ion (Mn2+) significantly improved cGAS-STING-IFNI pathway activation induced by X-ray in both normoxic and hypoxic glioma cells, thereby promoting the maturation and migration of DCs. The responses of cGAS-STING-IFNI pathway to ionizing radiation were mainly investigated under normoxic condition, but the experiments described here indicated that hypoxia could hinder the pathway activation. However, Mn2+ showed radiosensitizing effects on the pathway under either normoxic or hypoxic conditions demonstrating its potential as a radiosensitizer for glioma through activating an anti-tumor immune response. [ABSTRACT FROM AUTHOR]

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Community Eye Clinics (CEC) increase accessibility of specialist ophthalmic services in the community, reducing demand for tertiary eye services. This paper aims to evaluate the impact of CEC on first-visit referrals from Hougang Polyclinic (HOU) to Tan Tock Seng Hospital Ophthalmology Specialist Outpatient Clinic (SOC).A retrospective analysis was performed on first-visit referrals from Hougang Polyclinic (HOU) to Tan Tock Seng Hospital Ophthalmology Specialist Outpatient Clinic (SOC) over a similar 3-months period before and after the introduction of CEC in August 2018 (1 January to 31 March in 2018 and 2019, respectively). Data pertaining to patients’ presenting complaints, referral reasons, final diagnoses, follow-up plans, and need for ophthalmic intervention were obtained.We included 978 patients in our study. There was a 27.5% reduction in the number of first-visit referrals seen at SOC after the establishment of CEC. Patients were more likely to be referred on to sub-specialty eye clinics (10.8% vs. 12.9%, p= p = .304) and receive more ophthalmic interventions (15% vs. 16.3%, p = .066) than prior to CEC.The CEC provides greater accessibility to eye care within the community. Optometrists are upskilled to manage patients with stable eye conditions, whilst eye specialists can provide timely care to the SOC for patients with more severe eye conditions. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor (CAR)-T immunotherapy fails to treat solid tumors due in part to immunosuppressive microenvironment. Excess lactate produced by tumor glycolysis increases CAR-T immunosuppression. The mechanism of lactate inducing the formation of immunosuppressive microenvironment remains to be further explored. Methods: Immunocyte subpopulations and molecular characteristics were analyzed in the orthotopic xenografts of nude mice using flow cytometry assay and immunohistochemical staining after oxamate, a lactate dehydrogenase A (LDHA) inhibitor, and control T or CAR-T cells injection alone or in combination. RT-qPCR, western blot, flow cytometry, immunofluorescence, luciferase reporter assay, chromatin immunoprecipitation and ELISA were performed to measure the effect of lactate on the regulation of CD39, CD73 and CCR8 in cultured glioma stem cells, CD4 + T cells or macrophages. Results: Oxamate promoted immune activation of tumor-infiltrating CAR-T cells through altering the phenotypes of immune molecules and increasing regulatory T (Treg) cells infiltration in a glioblastoma mouse model. Lactate accumulation within cells upregulated CD39, CD73 and CCR8 expressions in both lactate-treated cells and glioma stem cells-co-cultured CD4 + T cells and macrophages, and intracellular lactate directly elevated the activities of these gene promotors through histone H3K18 lactylation. Conclusions: Utilizing lactate generation inhibitor not only reprogramed glucose metabolism of cancer stem cells, but also alleviated immunosuppression of tumor microenvironment and reduced tumor-infiltrating CAR-Treg cells, which may be a potential strategy to enhance CAR-T function in glioblastoma therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • The beta frequency strongest associated with motor slowing may differ from the individual beta peak at rest or largest movement-modulation frequency. • The timing of beta bursts and triggering of adaptive deep brain stimulation differ across varying frequencies in the beta range. • A clinical neurophysiological interrogation step can optimize the feedback signal selection for adaptive deep brain stimulation. Subthalamic nucleus (STN) beta activity (13–30 Hz) is the most accepted biomarker for adaptive deep brain stimulation (aDBS) for Parkinson's disease (PD). We hypothesize that different frequencies within the beta range may exhibit distinct temporal dynamics and, as a consequence, different relationships to motor slowing and adaptive stimulation patterns. We aim to highlight the need for an objective method to determine the aDBS feedback signal. STN LFPs were recorded in 15 PD patients at rest and while performing a cued motor task. The impact of beta bursts on motor performance was assessed for different beta candidate frequencies: the individual frequency strongest associated with motor slowing, the individual beta peak frequency, the frequency most modulated by movement execution, as well as the entire-, low- and high beta band. How these candidate frequencies differed in their bursting dynamics and theoretical aDBS stimulation patterns was further investigated. The individual motor slowing frequency often differs from the individual beta peak or beta-related movement-modulation frequency. Minimal deviations from a selected target frequency as feedback signal for aDBS leads to a substantial drop in the burst overlapping and in the alignment of the theoretical onset of stimulation triggers (to ∼ 75% for 1 Hz, to ∼ 40% for 3 Hz deviation). Clinical-temporal dynamics within the beta frequency range are highly diverse and deviating from a reference biomarker frequency can result in altered adaptive stimulation patterns. A clinical-neurophysiological interrogation could be helpful to determine the patient-specific feedback signal for aDBS. [ABSTRACT FROM AUTHOR]

Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or adapting actions depending on their outcome. However, the corresponding electrophysiological correlates in the basal ganglia and the extent to which these causally contribute to action adaptation in humans is unclear. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus, a core area of the basal ganglia, in 16 patients with Parkinson's disease (PD) on medication using temporarily externalized deep brain stimulation (DBS) electrodes. Patients as well as 16 age- and gender-matched healthy participants attempted to produce forces as close as possible to a target force to collect a maximum number of points. The target force changed over trials without being explicitly shown on the screen so that participants had to infer target force based on the feedback they received after each movement. Patients and healthy participants were able to adapt their force according to the feedback they received (P < 0.001). At the neural level, decreases in subthalamic beta (13 to 30 Hz) activity reflected poorer outcomes and stronger action adaptation in 2 distinct time windows (Pcluster-corrected < 0.05). Stimulation of the subthalamic nucleus reduced beta activity and led to stronger action adaptation if applied within the time windows when subthalamic activity reflected action outcomes and adaptation (Pcluster-corrected < 0.05). The more the stimulation volume was connected to motor cortex, the stronger was this behavioral effect (Pcorrected = 0.037). These results suggest that dynamic modulation of the subthalamic nucleus and interconnected cortical areas facilitates adaptive behavior. This study shows that activity in the subthalamic nucleus reflects action outcomes and consequent adaptation in humans. This can be modified through bursts of electrical stimulation, with the potential to restore healthy brain function in people with neurological disorders like Parkinson's disease. [ABSTRACT FROM AUTHOR]

The primary aim of this investigation was to improve the chiral separation performance of graphene oxide (GO) based composite membranes via tuning the interlayer spacing between GO sheets using the association of poly( L -Glutamic acid sodium), P L GA, onto the surface of GO sheets. Results show that: i) compared with conventional chiral separation membranes, these membranes exhibit superior chiral resolution properties, which are 1–2 orders of magnitude higher in the flux and greater in the enantioselectivity; ii) compared with pristine L-Glutamic modified GO membranes, they also afford a significant improvement in enantioselectivity with a slight reduction in flux. In present work, it is demonstrated that in such composite membranes, the incorporated P L GA can not only serve as an additional chiral recognizing agent, facilitating the transport of D-isomer of the chiral probe, but also as a kind of filler, reducing the size of pores or channels between GO sheets. Especially, both roles can significantly contribute to enhancing the enantioselectivitiy of composite membranes. Our findings indicate that the combination of GO-based materials and polypeptides might offer unusual control in the selectivity and the flux of the corresponding composite membranes, achieved by regulating the interlayer spacing between GO sheets, and thus such composite membranes have a potential to simultaneously facilitate high-flux and high-selectivity and a promising application in a great number of enantio- and bio-separations. [ABSTRACT FROM AUTHOR]

Background: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation. Objective: We aimed to explore if enhanced theta power was also present in STN and if stimulation‐induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia. Methods: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus. Results: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely‐tuned gamma oscillations, and an increase in aperiodic exponents in STN‐LFPs. Both power suppression and ERNA localize to STN. Based on this, single‐pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases. Conclusions: Our results show that STN stimulation–induced spectral changes are a nondisease‐specific response to high‐frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE−/− mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE−/− mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis. [ABSTRACT FROM AUTHOR]

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation. • The new quantification AFS comprehensively captures variations in amplitude and frequency stability of neural oscillations. • AFS quantification indicates better correlation than amplitude or frequency stability with symptom alleviation. • AFS can be implemented in real-time for adaptive deep brain stimulation. [ABSTRACT FROM AUTHOR]

Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson's disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson's disease, and that together these different states predict motor impairment with high fidelity. Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz. Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients' hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone. We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems. [ABSTRACT FROM AUTHOR]

Low-frequency oscillations in the basal ganglia are prominent in patients with Parkinson's disease off medication. Correlative and more recent interventional studies potentially implicate these rhythms in the pathophysiology of Parkinson's disease. However, effect sizes have generally been small and limited to bradykinesia. In this study, we investigate whether these effects extend to rigidity and are maintained in the on-medication state. We studied 24 sides in 12 patients on levodopa during bilateral stimulation of the STN at 5, 10, 20, 50, 130 Hz and in the off-stimulation state. Passive rigidity at the wrist was assessed clinically and with a torque-based mechanical device. Low-frequency stimulation at ≤20 Hz increased rigidity by 24 % overall ( p = 0.035), whereas high-frequency stimulation (130 Hz) reduced rigidity by 18 % ( p = 0.033). The effects of low-frequency stimulation (5, 10 and 20 Hz) were well correlated with each other for both flexion and extension ( r = 0.725 ± SEM 0.016 and 0.568 ± 0.009, respectively). Clinical assessments were unable to show an effect of low-frequency stimulation but did show a significant effect at 130 Hz ( p = 0.002). This study provides evidence consistent with a mechanistic link between oscillatory activity at low frequency and Parkinsonian rigidity and, in addition, validates a new method for rigidity quantification at the wrist. [ABSTRACT FROM AUTHOR]

Background: High‐frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor. Objective: We proposed to close the loop of thalamic stimulation by detecting tremor‐provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary. Methods: Eight patients with essential tremor participated in this study. Patient‐specific support vector machine classifiers were first trained using data recorded while the patient performed tremor‐provoking movements. Then, the trained models were applied in real‐time to detect these movements and triggered the delivery of stimulation. Results: Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor‐evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor‐free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation. Conclusions: The results suggest that responsive thalamic stimulation for essential tremor based on tremor‐provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

• Bursts of beta activity have been linked to motor impairment in Parkinson's disease. • Termination of bursts is associated with characteristic changes in oscillation shape. • These suggest input drive desynchronization, increased theta activity and phase slips. Phasic bursts of beta band synchronisation have been linked to motor impairment in Parkinson's disease (PD). However, little is known about what terminates bursts. We used the Hilbert–Huang transform to investigate beta bursts in the local field potential recorded from the subthalamic nucleus in nine patients with PD on and off levodopa. The sharpness of the beta waveform extrema fell as burst amplitude dropped. Conversely, an index of phase slips between waveform extrema, and the power of concurrent theta activity increased as burst amplitude fell. Theta activity was also increased on levodopa when beta bursts were attenuated. These phenomena were associated with reduction in coupling between beta phase and high gamma activity amplitude. We discuss how these findings may suggest that beta burst termination is associated with relative desynchronization of the beta drive, increase in competing theta activity and increased phase slips in the beta activity. We characterise the dynamical nature of beta bursts, thereby permitting inferences about underlying activities and, in particular, about why bursts terminate. Understanding the dynamical nature of beta bursts may help point to interventions that can cause their termination and potentially treat motor impairment in PD. [ABSTRACT FROM AUTHOR]

Background: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised.Methods: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings.Results: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz).Conclusions: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness. [ABSTRACT FROM AUTHOR]

Highlights • Beta desynchronization during leg movements involves higher beta frequencies. • Limb specific spectral changes evident for contralateral and ipsilateral movements. • Spatial distinction of limb-specific movements is evident at gamma frequencies. Abstract Objective Functional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson's disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements. Methods We recorded local field potentials (LFPs) from the subthalamic nucleus using segmented "directional" DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs. Results We found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies. Conclusion Limb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads. Significance These findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract At present, the separation of racemates is still a great challenge, since they are enantiomers, having similar chemical structures and physical properties. Here, we proposed a new strategy for efficiently separating chiral compounds, i.e., stereoselectively hydrolyzing the individual enantiomer of racemates via enzyme, followed by a simple magnetic separation using Fe 3 O 4 nanoparticles, may implement a complete resolution of racemates. In this work, d -aminoacylase was selected as enzyme, and phenylalanine and methionine as chiral models. The use of d -aminoacylase can hydrolyze d -enantiomer, while l -enantiomer cannot. Magnetic nanoparticles of Fe 3 O 4 @SiO 2 -NH 2 -COOH composites were designed and synthesized for the amidation reaction with the hydrolyzed d -amino acids from the mixture. With the help of a magnetic field, d -form amino acids can be readily separated at a large scale and the resultant resolving performances indicated that this method exhibited a higher selectivity, compared with common chiral separation techniques. The enantiomeric excess (e.e.) values are 75% and 98% for racemic N-acyl-phenylalanine and methionine, respectively, which solely rely on the hydrolysis capability of used enzymes. This result suggests that our method is feasible, simple, easy to scale-up and high-efficient for the chiral resolution. These findings demonstrate that this strategy could provide new opportunities for improving enantioseparation performances for a host of enantio- and bio-substance with both high-yield and high-selectivity. [ABSTRACT FROM AUTHOR]

Exaggerated activity in the beta band (13–35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment. [ABSTRACT FROM AUTHOR]