Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Temporal interference stimulation targets deep primate brain.

Temporal interference (TI) stimulation, a novel non-invasive stimulation strategy, has recently been shown to modulate neural activity in deep brain regions of living mice. Yet, it is uncertain if this method is applicable to larger brains and whether the electric field produced under traditional safety currents can penetrate deep regions as observed in mice. Despite recent model-based simulation studies offering positive evidence at both macro- and micro-scale levels, the absence of electrophysiological data from actual brains hinders comprehensive understanding and potential application of TI. This study aims to directly measure the spatiotemporal properties of the interfered electric field in the rhesus monkey brain and to validate the effects of TI on the human brain. Two monkeys were involved in the measurement, with implantation of several stereo-electroencephalography (SEEG) depth electrodes. TI stimulation was applied to anesthetized monkeys using two pairs of surface electrodes at differing stimulation parameters. Model-based simulations were also conducted and subsequently compared with actual recordings. Additionally, TI stimulation was administered to patients with motor disorders to validate its effects on motor symptoms. Through the integration of computational electric field simulation with empirical measurements, it was determined that the temporally interfering electric fields in the deep central regions are capable of attaining a magnitude sufficient to induce a subthreshold modulation effect on neural signals. Additionally, an improvement in movement disorders was observed as a result of TI stimulation. This study is the first to systematically measure the TI electric field in living non-human primates, offering empirical evidence that TI holds promise as a more focal and precise method for modulating neural activities in deep regions of a large brain. This advancement paves the way for future applications of TI in treating neuropsychiatric disorders.

Subthalamic and pallidal oscillations and their couplings reflect dystonia severity and improvements by deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear. OBJECTIVE: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment. METHODS: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy. RESULTS: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations. CONCLUSIONS: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. RESULTS: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. CONCLUSIONS: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson's disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson's disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait. Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson's disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking. We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials. These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel 'bandwidth model,' which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

Low-frequency oscillations link frontal and parietal cortex with subthalamic nucleus in conflicts.

Low-frequency oscillations (LFOs, 28 Hz) in the subthalamic nucleus(STN) are known to reflect cognitive conflict. However, it is unclear if LFOs mediate communication and functional interactions among regions implicated in conflict processing, such as the motor cortex (M1), premotor cortex (PMC), and superior parietal lobule (SPL). To investigate the potential contribution of LFOs to cognitive conflict mediation, we recorded M1, PMC, and SPL activities by right subdural electrocorticography (ECoG) simultaneously with bilateral STN local field potentials (LFPs) by deep brain stimulation electrodes in 13 patients with Parkinson's disease who performed the arrow version of the Eriksen flanker task. Elevated cue-related LFO activity was observed across patients during task trials, with the earliest onset in PMC and SPL. At cue onset, LFO power exhibited a significantly greater increase or a trend of a greater increase in the PMC, M1, and STN, and less increase in the SPL during high-conflict (incongruent) trials than in low-conflict (congruent) trials. The local LFO power increases in PMC, SPL, and right STN were correlated with response time, supporting the notion that these structures are critical hubs for cognitive conflict processing. This power increase was accompanied by increased functional connectivity between the PMC and right STN, which was correlated with response time across subjects. Finally, ipsilateral PMC-STN Granger causality was enhanced during high-conflict trials, with direction from STN to PMC. Our study indicates that LFOs link the frontal and parietal cortex with STN during conflicts, and the ipsilateral PMC-STN connection is specifically involved in this cognitive conflict processing.

Learning Protein Embedding to Improve Protein Fold Recognition Using Deep Metric Learning.

Protein fold recognition refers to predicting the most likely fold type of the query protein and is a critical step of protein structure and function prediction. With the popularity of deep learning in bioinformatics, protein fold recognition has obtained impressive progress. In this study, to extract the fold-specific feature to improve protein fold recognition, we proposed a unified deep metric learning framework based on a joint loss function, termed NPCFold. In addition, we also proposed an integrated machine learning model based on the similarity of proteins in various properties, termed NPCFoldpro. Benchmark experiments show both NPCFold and NPCFoldpro outperform existing protein fold recognition methods at the fold level, indicating that our proposed strategies of fusing loss functions and fusing features could improve the fold recognition level.

Local field potentials in Parkinson's disease: A frequency-based review.

Deep brain stimulation (DBS) surgery offers a unique opportunity to record local field potentials (LFPs), the electrophysiological population activity of neurons surrounding the depth electrode in the target area. With direct access to the subcortical activity, LFP research has provided valuable insight into disease mechanisms and cognitive processes and inspired the advent of adaptive DBS for Parkinson's disease (PD). A frequency-based framework is usually employed to interpret the implications of LFP signatures in LFP studies on PD. This approach standardizes the methodology, simplifies the interpretation of LFP patterns, and makes the results comparable across studies. Importantly, previous works have found that activity patterns do not represent disease-specific activity but rather symptom-specific or task-specific neuronal signatures that relate to the current motor, cognitive or emotional state of the patient and the underlying disease. In the present review, we aim to highlight distinguishing features of frequency-specific activities, mainly within the motor domain, recorded from DBS electrodes in patients with PD. Associations of the commonly reported frequency bands (delta, theta, alpha, beta, gamma, and high-frequency oscillations) to motor signs are discussed with respect to band-related phenomena such as individual tremor and high/low beta frequency activity, as well as dynamic transients of beta bursts. We provide an overview on how electrophysiology research in DBS patients has revealed and will continuously reveal new information about pathophysiology, symptoms, and behavior, e.g., when combining deep LFP and surface electrocorticography recordings.

Many-Body Chern Number from Statistical Correlations of Randomized Measurements.

One of the main topological invariants that characterizes several topologically ordered phases is the many-body Chern number (MBCN). Paradigmatic examples include several fractional quantum Hall phases, which are expected to be realized in different atomic and photonic quantum platforms in the near future. Experimental measurement and numerical computation of this invariant are conventionally based on the linear-response techniques that require having access to a family of states, as a function of an external parameter, which is not suitable for many quantum simulators. Here, we propose an ancilla-free experimental scheme for the measurement of this invariant, without requiring any knowledge of the Hamiltonian. Specifically, we use the statistical correlations of randomized measurements to infer the MBCN of a wave function. Remarkably, our results apply to disklike geometries that are more amenable to current quantum simulator architectures.

Application value of hand-sewn anastomosis in totally laparoscopic total gastrectomy for gastric cancer.

BACKGROUND: Digestive tract reconstruction in totally laparoscopic total gastrectomy can be divided into two types: instrument anastomosis and hand-sewn anastomosis. This study explored the feasibility and safety of hand-sewn sutures in esophagojejunostomy of totally laparoscopic total gastrectomy, compared with instrument anastomosis using an overlap linear cutter. METHODS: This retrospective cohort study was conducted from January 2017 to January 2020 at one institution. The clinical data of 50 patients who underwent totally laparoscopic total gastrectomy, with an average follow-up time of 12 months, were collected. The clinicopathologic data, short-term survival prognosis, and results of patients in the hand-sewn anastomosis (n=20) and the overlap anastomosis (n=30) groups were analyzed. RESULTS: There were no significant differences between the groups in sex, age, body mass index, American Society of Anesthesiologists score, tumor location, preoperative complications, abdominal operation history, tumor size, pTNM stage, blood loss, first postoperative liquid diet, exhaust time, or postoperative length of hospital stay. The hand-sewn anastomosis group had a significantly prolonged operation time (204±26.72min versus 190±20.90min, p=0.04) and anastomosis time (58±22.0min versus 46±15.97min, p=0.029), and a decreased operation cost (CNY 77,100±1700 versus CNY 71,900±1300, p<0.0001). Postoperative complications (dynamic ileus, abdominal infection, and pancreatic leakage) occurred in three patients (15%) in the hand-sewn anastomosis group and in four patients (13.3%) in the overlap anastomosis group (anastomotic leakage, anastomotic bleeding, dynamic ileus, and duodenal stump leakage). CONCLUSION: The hand-sewn anastomosis method of esophagojejunostomy under totally laparoscopic total gastrectomy is safe and feasible and is an important supplement to linear and circular stapler anastomosis. It may be more convenient regarding obesity, a relatively high position of the anastomosis, edema of the esophageal wall, and short jejunal mesentery.

Universal Logical Gates on Topologically Encoded Qubits via Constant-Depth Unitary Circuits.

A fundamental question in the theory of quantum computation is to understand the ultimate space-time resource costs for performing a universal set of logical quantum gates to arbitrary precision. Here we demonstrate that non-Abelian anyons in Turaev-Viro quantum error correcting codes can be moved over a distance of order of the code distance, and thus braided, by a constant depth local unitary quantum circuit followed by a permutation of qubits. Our gates are protected in the sense that the lengths of error strings do not grow by more than a constant factor. When applied to the Fibonacci code, our results demonstrate that a universal logical gate set can be implemented on encoded qubits through a constant depth unitary quantum circuit, and without increasing the asymptotic scaling of the space overhead. These results also apply directly to braiding of topological defects in surface codes. Our results reformulate the notion of braiding in general as an effectively instantaneous process, rather than as an adiabatic, slow process.

Subthalamic nucleus deep brain stimulation suppresses neuroinflammation by Fractalkine pathway in Parkinson's disease rat model.

Subthalamic nucleus deep brain stimulation (STN-DBS) is widely used to treat patients with Parkinson's disease (PD), and recent studies have shown that it is more beneficial for early stages, suggesting a potential neuroprotective effect. And the neuroinflammation plays an indispensable role in progress of PD. However, the underlying mechanisms are not well understood. The aim of this study was to investigate the effect of STN-DBS on neuroinflammation and the potential pathway. To address this question, we established a rat PD model by unilateral 6-hydroxydopamine injection into the left striatum and implanted stimulation leads into the ipsilateral STN to deliver electrical stimulation for a week. The neuroprotective effects of STN-DBS were examined by molecular biology techniques, including western blotting, immunohistochemistry and so on. We found that motor deficits were alleviated by STN-DBS, with increased survival of dopaminergic neurons in the substantia nigra (SN). Furthermore, STN-DBS decreased Fractalkine (CX3CL1) and its receptor (CX3CR1) expression. Meanwhile, the suppressed microglia activation and nuclear factor-κB expression, decrease in the levels of pro-inflammatory cytokine interleukin (IL)-1ß and IL-6 and increase in anti-inflammatory cytokine IL-4, downregulated IL-1 receptor, extracellular signal-regulated kinase (ERK) and cleaved-caspase3 were also observed in SN of PD models received STN-DBS. In conclusion, we observed a significant association between the suppressed neuroinflammation and STN-DBS, which may be attributed to CX3CL1/CX3CR1 signaling. These results provide novel insight into the mechanistic basis of STN-DBS therapy for PD.

Isolation and identification of two Serratia marcescens strains from silkworm, Bombyx mori.

Bacterial septicemia commonly occurs and usually cause huge losses in sericulture industry. Here, two pathogenic bacterial strains were isolated from dead silkworm and named as ZJ-1 and ZJ-2. Phenotypic and genotypic analysis results revealed that both of these two strains are closely related to Serratia marcescens (S. marcescens). The morphological as well as physiological and biochemical characteristics of ZJ-1 were accordant with S. marcescens mentioned in Bergey's manual of determinative bacteriology, whereas ZJ-2 showed some discrepancies such as the utilization of malonate and starch, fermentation of maltose and sucrose, and tests of urease, etc. Surprisingly, ZJ-2 could produce red pigment at high temperature (37°) but ZJ-1 could not. Besides, by analyzing the lethal concentration 50 (LC50) of ZJ-1 and ZJ-2, it was found that the virulence of ZJ-2 was lower than that of ZJ-1. These results revealed that ZJ-1 and ZJ-2 were two different strains of S. marcescens and that ZJ-2 was expected to be a safe (low-toxicity) and efficient strain for the production of red pigment. Nonetheless, further research in molecular level is needed to understand the regulation mechanism of pigment production and infection of ZJ-2.

Identification and subcellular localization of splicing factor arginine/serine-rich 10 in the microsporidian Nosema bombycis.

Splicing factors are important components of RNA editing in eukaryotic organisms and can produce many functional and coding genes, which is an indispensable step for the correct expression of corresponding proteins. In this study, we identified splicing factor arginine/serine-rich 10 protein in the microsporidian Nosema bombycis and named it NbSRSF10. The NbSRSF10 gene contains a complete ORF of 1449 bp in length that encodes a 482-amino acid polypeptide. The isoelectric point (pI) of the protein encoded by NbSRSF10 gene was 4.94. NbSRSF10 has a molecular weight of 54.6 kD and has no signal peptide. NbSRSF10 is comprised of arginine (11.41%), glutamic acid (11.41%) and serine (9.54%) among the total amino acids, and 7 α-helix, 7 ß-sheet and 15 random coils in secondary structure, and contains 71 phosphorylation sites, 22 N-glycosylation sites and 20 O-glycosylation sites. The three-dimensional structure of NbSRSF10 is similar to that of transformer-2 beta of Homo sapiens (hTra2-ß). Indirect immunofluorescence showed that the NbSRSF10 is localized in the cytoplasm of the dormant microsporidian spore and is transferred to the nuclei when N. bombycis develops into the proliferative and sporogonic phase. qPCR revealed that the relative expression of NbSRSF10 increased in the meronts stage and was found at a relatively low level in the sporogonic phase of development of N. bombycis, and was up-regulated again during infection in the host cell and early proliferative phase of second life cycle. These results suggested that the NbSRSF10 may participate in the whole life cycle and play an important role in transcription regulation of N. bombycis.

lncRNA CCAT1 contributes to the growth and invasion of gastric cancer via targeting miR-219-1.

Gastric cancer (GC) is one of the most malignant tumors that seriously threaten human health. Increased reports have indicated that long noncoding RNAs (lncRNAs) are associated with GC. This study aims to investigate the regulatory role of colon cancer-associated transcript-1 (CCAT1) in GC. The results exhibited the fact that CCAT1 was expressed higher in 57 GC tissue samples than in 57 paired adjacent normal tissue samples. The expression of CCAT1 was also increased in GC cell lines (MKN45, Hs746T, and SGC-7901) compared with the gastric epithelial cell line GES-1. Besides this, decreased cell proliferation with increased cell apoptosis was detected in SGC-7902 cells transfected with CCAT1 short hairpin RNA (shRNA). At the same time, a lower cell invasion ability was measured in SCG-7901 cells transfected with CCAT1 shRNA.In addition, miR-219-1 was predicted and convinced a direct target of CCAT1. The expression of miR-219-1 was decreased in GC tissues and GC cell lines. Further studies demonstrated that the roles of CCAT1 in cell proliferation, apoptosis, and invasion were inhibited by miR-219-1. Finally, in vivo experiment indicated that tumor growth of GC was suppressed through knockdown of CCAT1. In conclusion, these results suggested that CAT1 promotes the tumorigenesis and progression of GC by negatively regulating miR-219-1.

Photon Pair Condensation by Engineered Dissipation.

Dissipation can usually induce detrimental decoherence in a quantum system. However, engineered dissipation can be used to prepare and stabilize coherent quantum many-body states. Here, we show that, by engineering dissipators containing photon pair operators, one can stabilize an exotic dark state, which is a condensate of photon pairs with a phase-nematic order. In this system, the usual superfluid order parameter, i.e., single-photon correlation, is absent, while the photon pair correlation exhibits long-range order. Although the dark state is not unique due to multiple parity sectors, we devise an additional type of dissipators to stabilize the dark state in a particular parity sector via a diffusive annihilation process which obeys Glauber dynamics in an Ising model. Furthermore, we propose an implementation of these photon pair dissipators in circuit-QED architecture.

Scale-Invariant Continuous Entanglement Renormalization of a Chern Insulator.

The multiscale entanglement renormalization ansatz (MERA) postulates the existence of quantum circuits that renormalize entanglement in real space at different length scales. Chern insulators, however, cannot have scale-invariant discrete MERA circuits with a finite bond dimension. In this Letter, we show that the continuous MERA (cMERA), a modified version of MERA adapted for field theories, possesses a fixed point wave function with a nonzero Chern number. Additionally, it is well known that reversed MERA circuits can be used to prepare quantum states efficiently in time that scales logarithmically with the size of the system. However, state preparation via MERA typically requires the advent of a full-fledged universal quantum computer. In this Letter, we demonstrate that our cMERA circuit can potentially be realized in existing analog quantum computers, i.e., an ultracold atomic Fermi gas in an optical lattice with light-induced spin-orbit coupling.

The Accuracy and Feasibility of Robotic Assisted Lead Implantation in Nonhuman Primates.

OBJECTIVES: Deep brain stimulation (DBS) and stereo-electroencephalography (SEEG) electrode implantation are the most important and frequent manipulations in nonhuman primates (NHP) neuromodulation research. However, traditional methods tend to be arduous and inaccurate. MATERIALS AND METHODS: Twelve adult male rhesus monkeys were selected for the study, with six subthalamic nucleus (STN) DBS, six anterior nucleus of the thalamus (ANT) DBS and six hippocampus-SEEG (Hippo-SEEG) electrodes implantation. Mean Euclidean errors of entrance and the target were calculated by postoperative image fusion, and the correlation between entrance and target error, as well as the differences among the various manipulations, were analyzed. The accuracy of target was further confirmed by gross anatomy examination. Moreover, the time consumption was recorded. RESULTS: The mean (±SD) Euclidean errors of the target point and entry point of the three manipulations were STN-DBS: 1.05 ± 0.54 mm and 0.52 ± 0.17 mm; ANT-DBS: 1.12 ± 0.74 mm and 0.58 ± 0.24 mm; and Hippo-SEEG: 2.68 ± 1.03 mm and 1.47 ± 0.63 mm. Significant differences were observed in both target and entry point errors between the DBS and Hippo-SEEG groups, with superior accuracy in the DBS group. The entrance errors had a significantly positive correlation with the target errors in the STN-DBS and Hippo-SEEG groups. Moreover, the time consumption in robotic surgery was much shorter than that in the traditional method, without any severe complications. CONCLUSION: The application of robot-assisted lead implantation in NHP neuromodulation research is feasible, accurate, safe, and efficient, and can prospectively be beneficial to neurological studies.