Demonstrating Path-Independent Anyonic Braiding on a Modular Superconducting Quantum Processor.

Anyons, exotic quasiparticles in two-dimensional space exhibiting nontrivial exchange statistics, play a crucial role in universal topological quantum computing. One notable proposal to manifest the fractional statistics of anyons is the toric code model; however, scaling up its size through quantum simulation poses a serious challenge because of its highly entangled ground state. In this Letter, we demonstrate that a modular superconducting quantum processor enables hardware-pragmatic implementation of the toric code model. Through in-parallel control across separate modules, we generate a 10-qubit toric code ground state in four steps and realize six distinct braiding paths to benchmark the performance of anyonic statistics. The path independence of the anyonic braiding statistics is verified by correlation measurements in an efficient and scalable fashion. Our modular approach, serving as a hardware embodiment of the toric code model, offers a promising avenue toward scalable simulation of topological phases, paving the way for quantum simulation in a distributed fashion.

Association of time spent outdoors with the risk of Parkinson's disease: a prospective cohort study of 329,359 participants.

BACKGROUND: Studies on the association between time spent outdoors and the development of Parkinson's disease (PD) are lacking, and whether this relationship differs in different subgroups (age, sex) remains unclear. OBJECTIVE: We here examined the association between time spent outdoors and the incidence of PD in different seasons. METHODS: This study included 329,359 participants from the UK Biobank. Data regarding hours spent outdoors during a typical day were obtained through questionnaires. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for the association between exposure to outdoors duration and PD incidence. Restricted cubic spline was used to explore the potential nonlinear relationship between time spent outdoors and PD risk. To explore the potential mechanisms of time spent outdoors effecting the risk of PD incidence, their association with serum vitamin D was further analysed separately. RESULTS: During a median follow-up of 13.57 years, 2,238 participants developed PD. In summer, time spent outdoors > 5.0 h/day was associated with a reduced PD risk compared with ≤ 2.0 h/day (HR = 0.84, 95% CI, 0.74-0.95). In winter too, time spent outdoors > 2.0 h/day was also associated with a reduced PD risk compared with ≤ 1.0 h/day (HR = 0.85, 95% CI, 0.76-0.94). For annual average time spent outdoors, participants who went outdoors for more than 3.5 h/day had a reduced PD risk than those who went outdoors for ≤ 1.5 h/day (HR = 0.85, 95% CI, 0.75-0.96). Additionally, sex and age differences were observed in the association between time spent outdoors and the PD risk. Moreover, Time spent outdoors was observed to be positively associated with serum vitamin D levels. Compared with serum vitamin D-deficient participants, the risk of PD was reduced by 15% in the sufficient participants. CONCLUSION: In the total population, higher time spent outdoors was linked to a reduced PD risk. However, this association may vary among different age or sex groups.

Analysis of factors influencing the recurrence of diabetic foot ulcers.

OBJECTIVE: The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate. METHODS: A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n = 84) and a non-recurrence group (n = 127). The following data were collected and analyzed for the two groups of patients: general information, foot information, laboratory indicators, diabetes comorbidities, and complications. RESULTS: (1) The overall recurrence rate of diabetic foot ulcers (DFU) within 2 years was 39.8%, indicating a high recurrence rate. (2) Significant differences were observed between the two patient groups in terms of BMI, HbA1c, TBIL, CRP, financial situation, foot deformity, first ulcer on the sole of the foot, previous amputation history, Wagner grade of the first ulcer, osteomyelitis, DFU duration (>60 days), lower limb vascular reconstruction, peripheral arterial disease (PAD), and diabetic peripheral neuropathy (DPN) (t = 2.455; Z = -1.988, -3.731, -3.618; χ2 = 7.88, 5.004, 3.906, 17.178, 16.237, 5.007, 24.642, 4.782, 29.334, 10.253). No significant differences were found for the other indicators. (3) Logistic regression analysis revealed that TBIL (OR = 0.886, p = 0.036) was a protective factor against ulcer recurrence. In contrast, PAD, previous amputation history, DPN, and the first ulcer on the sole of the foot (OR = 3.987, 6.758, 4.681, 2.405; p < 0.05 or p < 0.01) were identified as risk factors for ulcer recurrence. CONCLUSION: Early screening and preventive education targeting high-risk factors such as DPN, PAD and the initial ulcer location on the sole of the foot are essential to mitigate the high long-term recurrence rate of DFU. Furthermore, the protective role of TBIL in preventing ulcer recurrence underscores the importance of monitoring bilirubin levels as part of a comprehensive management strategy for DFU patients.

Optimized expression of Peptidyl-prolyl cis/transisomerase cyclophilinB with prokaryotic toxicity from Sporothrix globosa.

Cyclophilin B (CypB), a significant member of immunophilins family with peptidyl-prolyl cis-trans isomerase (PPIase) activity, is crucial for the growth and metabolism of prokaryotes and eukaryotes. Sporothrix globosa (S. globosa), a principal pathogen in the Sporothrix complex, causes sporotrichosis. Transcriptomic analysis identified the cypB gene as highly expressed in S. globosa. Our previous study demonstrated that the recombinant Escherichia coli strain containing SgcypB gene failed to produce sufficient product when it was induced to express the protein, implying the potential toxicity of recombinant protein to the bacterial host. Bioinformatics analysis revealed that SgCypB contains transmembrane peptides within the 52 amino acid residues at the N-terminus and 21 amino acids near the C-terminus, and 18 amino acid residues within the cytoplasm. AlphaFold2 predicted a SgCypB 3D structure in which there is an independent PPIase domain consisting of a spherical extracellular part. Hence, we chose to express the extracellular domain to yield high-level recombinant protein with PPIase activity. Finally, we successfully produced high-yield, truncated recombinant CypB protein from S. globosa (SgtrCypB) that retained characteristic PPIase activity without host bacterium toxicity. This study presents an alternative expression strategy for proteins toxic to prokaryotes, such as SgCypB. ONE-SENTENCE SUMMARY: The recombinant cyclophilin B protein of Sporothrix globosa was expressed successfully by retaining extracellular domain with peptidyl-prolyl cis-trans isomerase activity to avoid toxicity to the host bacterium.

Nutritional screening and assessment tools for patients with cirrhosis based on the Global Leadership Initiative on Malnutrition criteria.

BACKGROUND: Malnutrition is highly prevalent and associated with complications and mortality in patients with cirrhosis. METHODS: This was a prospective observational study. Patients with cirrhosis were screened using the Nutritional Risk Screening 2002, the Royal Free Hospital-Nutritional Prioritizing Tool and the Skeletal Muscle Index. Then, the sensitivity, specificity, positive and negative predictive values, and consistency with the Global Leadership Initiative on Malnutrition criteria results were calculated. We also analysed the association between nutritional status and short-term prognosis. RESULTS: We enrolled 125 patients with cirrhosis, of whom 59.20% and 60.00% were malnourished based on the Global Leadership Initiative on Malnutrition criteria and Skeletal Muscle Index. Some 53.60% and 65.60%, respectively, were classified medium-to-high nutritional risk by Nutritional Risk Screening 2002 and the Royal Free Hospital-Nutritional Prioritizing Tool. The Royal Free Hospital-Nutritional Prioritizing Tool had the best predictive value, and it was more sensitive and had a better negative predictive value than the Nutritional Risk Screening 2002 Tool. The Skeletal Muscle Index also had good sensitivity and predictive value. The Royal Free Hospital-Nutritional Prioritizing Tool, Skeletal Muscle Index and Global Leadership Initiative on Malnutrition criteria showed high concordance. The 3- and 6-month mortality rates were significantly higher for patients with moderate-to-high nutritional risk or malnutrition, regardless of the tool. CONCLUSIONS: When assessing cirrhosis with the Global Leadership Initiative on Malnutrition criteria, the Royal Free Hospital-Nutritional Prioritizing Tool is best for nutritional screening and the Skeletal Muscle Index is also a good nutritional assessment tool.

Ginsenoside Rg1 attenuates D-galactose-induced neural stem cell senescence via the Sirt1-Nrf2-BDNF pathway.

With the ageing of society's population, neurodegenerative diseases have become an important factor affecting the quality of life and mortality in the elderly. Since its physiopathological processes are complex and the authorized medications have recently been shown to have several adverse effects, the development of safe and efficient medications is urgently needed. In this study, we looked at how ginsenoside Rg1 works to postpone neural stem cell ageing and brain ageing, giving it a solid scientific foundation for use as a therapeutic therapy for neurodegenerative diseases.

Current coffee consumption is associated with decreased striatal dopamine transporter availability in Parkinson's disease patients and healthy controls.

BACKGROUND: Coffee is the most widely consumed psychostimulant worldwide. Emerging evidence indicates that coffee consumption habit significantly reduces the risk of developing Parkinson's disease (PD). However, the effect of coffee consumption on nigrostriatal dopaminergic neurodegeneration is still largely unknown. We therefore aim to investigate the role of coffee consumption in nigrostriatal dopaminergic neurodegeneration using dopamine transporter (DAT) imaging in PD and healthy controls (HC). METHODS: A total of 138 PD patients and 75 HC with questionnaires about coffee consumption, and DAT scans were recruited from the Parkinson's Progression Markers Initiative cohort. Demographic, clinical, and striatal DAT characteristics were compared across subgroups of current, former, and never coffee consumers in PD and HC, respectively. Furthermore, partial correlation analyses were performed to determine whether there was a relationship between coffee cups consumed per day and striatal DAT characteristics in each striatal region. In addition, the factors that may have influenced the loss of nigrostriatal dopaminergic neurons were included in multiple linear regression analyses to identify significant contributing factors to DAT availability in each striatal region. RESULTS: PD patients had lower DAT availability in each striatal region than HC (p < 0.001). In PD patients, there were significant differences in DAT availability in the caudate (p = 0.008, Bonferroni corrected) across three PD subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.01) and never coffee consumers (p = 0.022). In HC, there were significant differences in DAT availability in the caudate (p = 0.031, Bonferroni uncorrected) across three HC subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.022). Moreover, correlation analysis revealed that cups per day were negatively correlated with DAT availability in the caudate in current consumers of PD patients (r = - 0.219, p = 0.047). In addition, multiple linear regression analyses showed that current coffee consumption remained an independent predictor of decreased DAT availability in the caudate in PD patients and HC. CONCLUSIONS: This study demonstrates that current coffee consumption is associated with decreased striatal DAT availability in the caudate. However, the effects of caffeine on striatal DAT may fade and disappear after quitting coffee consumption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01141023.

Application of rhein as an immunostimulant controls spring viremia of carp virus infection.

In recent years, the exploration of natural compounds possessing both immunostimulatory and antiviral activities has attracted growing attention in aquaculture research. Consequently, the pursuit of identifying natural products exhibiting anti-SVCV potential as immunostimulants holds significant promise, offering a pathway to mitigate the economic ramifications inflicted by SVCV outbreaks in aquaculture settings. Among them, rhein emerges as a particularly compelling contender. Boasting a widespread distribution, well-established extraction methods, and multiple biological activities, it has exhibited the capacity to enhance the antiviral activity of host cells in vitro by blocking the viral internalization process, with a peak inhibition rate of 44.0%. Based on this intervention, rhein inhibited apoptosis and mitochondrial damage triggered by SVCV infection, ultimately producing a significant antiviral effect. Moving beyond the laboratory setting, rhein's efficacy translates effectively into in vivo scenarios. It has demonstrated substantial antiviral potency by increasing the expression of antiviral-related genes, most notably, retinoic acid-inducible gene I (RIG-I), interferon-φ (IFN-φ) and IFN-stimulated gene product 15 (ISG15). In concert with this genetic modulation, rhein efficiently reduces the viral load, precipitating a consequential enhancement in the survival rate of SVCV-infected fish, elevating it to an encouraging 16%. In conclusion, the outcomes of our investigation offer a compelling testament to rhein's potential as a valuable immunomodulator in the battle against SVCV infections in aquaculture, and the remarkable attributes exhibited by rhein underscore its viability for future commercial deployment.

Involvement of Microplastics in the Conflict Between Host Immunity Defense and Viral Virulence: Promoting the Susceptibility of Shrimp to WSSV Infection.

As the concentration of microplastics/microspheres (MPs) in coastal and estuarine regions increases, the likelihood of disease outbreaks and epidemics also rises. Our study investigated the impact of polyvinyl chloride MPs (PVC-MPs) on white spot syndrome virus (WSSV) infection in shrimp. The results revealed that PVC-MPs obviously increased WSSV replication in vivo, leading to a high mortality rate among the larvae and facilitating the horizontal transmission of WSSV. Furthermore, the data of WSSV loads detected together with qPCR, agarose gel electrophoresis, and flow cytometry approaches indicated that PVC-MPs could interact with the virus to prolong survival and maintain the virulence of WSSV at different temperatures and pH values. In terms of host resistance, metabolomics and transcriptomics analysis demonstrated that exposure to PVC-MPs upregulated metabolic concentrations and gene expressions associated with phospholipid metabolism that were associated with innate immunity responses. Particularly, PVC-MPs stimulated the synthesis of phosphatidylcholine (PC) and induced lipid peroxidation. The inhibition of PC on Stimulator of Interferon Genes (STING) translocation from the endoplasmic reticulum to the Golgi apparatus reduces expression of the innate immunity genes (IFN-like genes Vago4 and Vago5) regulated by STING signaling pathways, resulting in a significant decrease in the shrimp's resistance to WSSV infection. Notably, a recovery operation in which the exposed larvae were transferred to a MPs-free aquatic environment led to decreased WSSV infectivity over time, indicating the restoration of antiviral properties in shrimp. Overall, these findings highlight that MPs promote shrimp susceptibility to WSSV in two aspects: host immune defense and viral virulence.

Satb2 Regulates EphA7 to Control Soma Spacing and Self-Avoidance of Cortical Pyramidal Neurons.

Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.

Labor Neuraxial Analgesia and Its Association With Perinatal Outcomes in China in 2015-2016: A Propensity Score-Matched Analysis.

BACKGROUND: The use of labor neuraxial analgesia (NA) in China has increased significantly in the past decade, and the current rate of use is unknown. This study aimed to describe the epidemiology of NA based on a large multicenter cross-sectional survey, the China Labor and Delivery Survey (CLDS) (2015-2016), and to evaluate the association between NA and intrapartum caesarean delivery (CD) and maternal and neonatal outcomes. METHODS: The CLDS was a facility-based cross-sectional investigation with a cluster random sampling scheme conducted from 2015 to 2016. A specific weight was assigned to each individual based on the sampling frame. Logistic regression was adopted to analyze the factors associated with the use of NA. A propensity score matching scheme was used to analyze the associations between NA and intrapartum CD and perinatal outcomes. RESULTS: A total of 51,488 vaginal deliveries or intrapartum CD were included in our study, excluding prelabor CDs. The weighted NA rate was 17.3% (95% confidence interval [CI], 16.6-18.0) in this survey population. Nulliparous, previous CD, hypertensive disorders, and labor augmentation were associated with higher use of NA. In the propensity score-matched analysis, NA was associated with reduced risks of intrapartum CD, especially intrapartum CD by maternal request (adjusted odds ratio [aOR], 0.68; 95% CI, 0.60-0.78 and aOR, 0.48; 95% CI, 0.30-0.76, respectively), 3rd or 4th degree perineal laceration (aOR, 0.36; 95% CI, 0.15-0.89), and 5-minute Apgar score ≤3 (aOR, 0.15; 95% CI, 0.03-0.66). CONCLUSIONS: The use of NA may be associated with improved obstetric outcomes, including fewer intrapartum CD, less birth canal trauma, and better neonatal outcomes in China.

Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China.

BACKGROUND: The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. METHODS: A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. RESULTS: Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. CONCLUSIONS: Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

A meta-analysis on the efficacy of vacuum sealing drainage combined with autologous platelet-rich plasma in the treatment of Grade 2 and Grade 3 diabetic foot ulcers.

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.

[Identifying Depressive Disorder With Sleep Electroencephalogram Data: A Study Based on Deep Learning].

Objective: To explore the effectiveness of using deep learning network combined Vision Transformer (ViT) and Transformer to identify patients with depressive disorder on the basis of their sleep electroencephalogram (EEG) signals. Methods: The sleep EEG signals of 28 patients with depressive disorder and 37 normal controls were preprocessed. Then, the signals were converted into image format and the feature information on frequency domain and spatial domain was retained. After that, the images were transmitted to the ViT-Transformer coding network for deep learning of the EEG signal characteristics of the rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with depressive disorder and those in normal controls, respectively, and to identify patients with depressive disorder. Results: Based on the ViT-Transformer network, after examining different EEG frequencies, we found that the combination of delta, theta, and beta waves produced better results in identifying depressive disorder. Among the different EEG frequencies, EEG signal features of delta-theta-beta combination waves in REM sleep achieved 92.8% accuracy and 93.8% precision for identifying depression, with the recall rate of patients with depression being 84.7%, and the F0.5 value being 0.917±0.074. When using the delta-theta-beta combination EEG signal features in NREM sleep to identify depressive disorder, the accuracy was 91.7%, the precision was 90.8%, the recall rate was 85.2%, and the F0.5 value was 0.914±0.062. In addition, through visualization of the sleep EEG of different sleep stages for the whole night, it was found that classification errors usually occurred during transition to a different sleep stage. Conclusion: Using the deep learning ViT-Transformer network, we found that the EEG signal features in REM sleep based on delta-theta-beta combination waves showed better effect in identifying depressive disorder.

[Analysis and Research on Intelligent Management and Control System of Reusable Medical Devices].

Focusing on the influencing factors of the operation and processing process of reusable medical devices, the management problems of reusable medical devices are analyzed from the processing processes of device assembly, packaging, handover, inventory and information recording. In the specific practice of designing the intelligent management and control system of reusable medical devices, the medical processes in different periods from device addition, packaging, disinfection, transfer, transportation, distribution, recycling to scrapping are integrated into the intelligent service system. Through the changes of medical device treatment, this study comprehensively explores the innovative ideas and specific problems in the construction of intelligent process system of hospital disinfection supply center.

Characterization of Histidine Functionalization and Its Timing in the Biosynthesis of Ribosomally Synthesized and Posttranslationally Modified Thioamitides.

Thioamitides are ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products that hold great potential in anticancer drug development. Members in this RiPP family feature a thioamidated peptidyl chain conjugated with a macrocyclic ring system that contains two nonproteinogenic residues, 2-aminovinyl-cysteine (AviCys) and ß-hydroxy-N,N-dimethyl-l-histidine (hdmHis). Focusing on the hdmHis residue that is unique to thioamitides, we report the enzymatic process for His functionalization and, more importantly, the timing of its related reactions with the other posttranslational modifications (PTMs) involved in thioamitide biosynthesis. His functionalization involves the activities of an S-adenosyl-l-methionine-dependent protein and a 2-oxoglutarate-Fe(II) monooxygenase for His bis-N-dimethylation and subsequent ß-hydroxylation in a highly ordered manner. This process relies on the leader peptide sequence of the precursor peptide and on the establishment of the AviCys-containing, C-terminal macrocyclic ring system in particular. In contrast, prior peptide thioamidation is not required. Knowledge gained from the catalytic logic, specificity, and compatibility of His functionalization greatly furthers our understanding of the process through which nature develops thioamitides from a ribosomally synthesized peptide precursor.

Scalable Method for Eliminating Residual ZZ Interaction between Superconducting Qubits.

Unwanted ZZ interaction is a quantum-mechanical crosstalk phenomenon which correlates qubit dynamics and is ubiquitous in superconducting qubit systems. It adversely affects the quality of quantum operations and can be detrimental in scalable quantum information processing. Here we propose and experimentally demonstrate a practically extensible approach for complete cancellation of residual ZZ interaction between fixed-frequency transmon qubits, which are known for long coherence and simple control. We apply to the intermediate coupler that connects the qubits a weak microwave drive at a properly chosen frequency in order to noninvasively induce an ac Stark shift for ZZ cancellation. We verify the cancellation performance by measuring vanishing two-qubit entangling phases and ZZ correlations. In addition, we implement a randomized benchmarking experiment to extract the idling gate fidelity which shows good agreement with the coherence limit, demonstrating the effectiveness of ZZ cancellation. Our method allows independent addressability of each qubit-qubit connection and is applicable to both nontunable and tunable couplers, promising better compatibility with future large-scale quantum processors.

ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors.

Genome-wide association studies uncovered the association of ZNF804A (Zinc-finger protein 804A) with schizophrenia (SZ). In vitro data have indicated that ZNF804A might exert its biological roles by regulating spine and neurite morphogenesis. However, no in vivo data are available for the role of ZNF804A in psychiatric disorders in general, SZ in particular. We generated ZFP804A mutant mice, and they showed deficits in contextual fear and spatial memory. We also observed the sensorimotor gating impairment, as revealed by the prepulse inhibition test, but only in female ZFP804A mutant mice from the age of 6 months. Notably, the PPI difference between the female mutant and control mice was no longer existed with the administration of Clozapine or after the ovariectomy. Hippocampal long-term potentiation was normal in both genders of the mutant mice. Long-term depression was absent in male mutants, but facilitated in the female mutants. Protein levels of hippocampal serotonin-6 receptor and GABAB1 receptor were increased, while those of cortical dopamine 2 receptor were decreased in the female mutants with no obvious changes in the male mutants. Moreover, the spine density was reduced in the cerebral cortex and hippocampus of the mutant mice. Knockdown of ZFP804A impaired the neurite morphogenesis of cortical and hippocampal neurons, while its overexpression enhanced neurite morphogenesis only in the cortical neurons in vitro. Our data collectively support the idea that ZFP804A/ZNF804A plays important roles in the cognitive functions and sensorimotor gating, and its dysfunction may contribute to SZ, particularly in the female patients.

mGluR5/ERK signaling regulated the phosphorylation and function of glycine receptor α1ins subunit in spinal dorsal horn of mice.

Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino-acid insert within the TM3-TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission.

Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory.

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK-/- mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue-cue associative memory.