A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic.

BACKGROUND AND PURPOSE: There is concern that subvisible aggregates in biotherapeutic drug products pose a risk to patient safety. We investigated the threshold of biotherapeutic aggregates needed to induce immunogenic responses. METHODS AND RESULTS: Highly aggregated samples were tested in cell-based assays and induced cellular responses in a manner that depended on the number of particles. The threshold of immune activation varied by disease state (cancer, rheumatoid arthritis, allergy), concomitant therapies, and particle number. Compared to healthy donors, disease state patients showed an equal or lower response at the late phase (7 days), suggesting they may not have a higher risk of responding to aggregates. Xeno-het mice were used to assess the threshold of immune activation in vivo. Although highly aggregated samples (~ 1,600,000 particles/mL) induced a weak and transient immunogenic response in mice, a 100-fold dilution of this sample (~ 16,000 particles/mL) did not induce immunogenicity. To confirm this result, subvisible particles (up to ~ 18,000 particles/mL, containing aggregates and silicone oil droplets) produced under representative administration practices (created upon infusion of a drug product through an IV catheter) did not induce a response in cell-based assays or appear to increase the rate of adverse events or immunogenicity during phase 3 clinical trials. CONCLUSION: The ability of biotherapeutic aggregates to elicit an immune response in vitro, in vivo, and in the clinic depends on high numbers of particles. This suggests that there is a high threshold for aggregates to induce an immunogenic response which is well beyond that seen in standard biotherapeutic drug products.

Abnormal dynamic reconfiguration of the large-scale functional network in schizophrenia during the episodic memory task.

Episodic memory deficits are the core feature in schizophrenia (SCZ). Numerous studies have revealed abnormal brain activity associated with this disorder during episodic memory, however previous work has only relied on static analysis methods that treat the brain as a static monolithic structure, ignoring the dynamic features at different time scales. Here, we applied dynamic functional connectivity analysis to functional magnetic resonance imaging data during episodic memory and quantify integration and recruitment metrics to reveal abnormal dynamic reconfiguration of brain networks in SCZ. In the specific frequency band of 0.06-0.125 Hz, SCZ showed significantly higher integration during encoding and retrieval, and the abnormalities were mainly in the default mode, frontoparietal, and cingulo-opercular modules. Recruitment of SCZ was significantly higher during retrieval, mainly in the visual module. Interestingly, interactions between groups and task status in recruitment were found in the dorsal attention, visual modules. Finally, we observed that integration was significantly associated with memory performance in frontoparietal regions. Our findings revealed the time-varying evolution of brain networks in SCZ, while improving our understanding of cognitive decline and other pathophysiologies in brain diseases.

Gender effects on the controllability of hemispheric white matter networks.

Male and female adults exhibited significant group differences in brain white matter (WM) asymmetry and WM network controllability. However, gender differences in controllability of hemispheric WM networks between males and females remain to be determined. Based on 1 principal atlas and 1 replication atlas, this work characterized the average controllability (AC) and modal controllability (MC) of hemispheric WM network based on 1 principal dataset and 2 replication datasets. All results showed that males had higher AC of left hemispheric networks than females. And significant hemispheric asymmetry was revealed in regional AC and MC. Furthermore, significant gender differences in the AC asymmetry were mainly found in regions lie in the frontoparietal network, and the MC asymmetry was found in regions involving auditory and emotion process. Finally, we found significant associations between regional controllability and cognitive features. Taken together, this work could provide a novel perspective for understanding gender differences in hemispheric WM asymmetry and cognitive function between males and females.

Altered higher-order coupling between brain structure and function with embedded vector representations of connectomes in schizophrenia.

It has been shown that the functional dependency of the brain exists in both direct and indirect regional relationships. Therefore, it is necessary to map higher-order coupling in brain structure and function to understand brain dynamic. However, how to quantify connections between not directly regions remains unknown to schizophrenia. The word2vec is a common algorithm through create embeddings of words to solve these problems. We apply the node2vec embedding representation to characterize features on each node, their pairwise relationship can give rise to correspondence relationships between brain regions. Then we adopt pearson correlation to quantify the higher-order coupling between structure and function in normal controls and schizophrenia. In addition, we construct direct and indirect connections to quantify the coupling between their respective functional connections. The results showed that higher-order coupling is significantly higher in schizophrenia. Importantly, the anomalous cause of coupling mainly focus on indirect structural connections. The indirect structural connections play an essential role in functional connectivity-structural connectivity (SC-FC) coupling. The similarity between embedded representations capture more subtle network underlying information, our research provides new perspectives for understanding SC-FC coupling. A strong indication that the structural backbone of the brain has an intimate influence on the resting-state functional.

Abnormal information interaction in multilayer directed network based on cross-frequency integration of mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been reported to result in abnormal cross-frequency integration. However, previous studies have failed to consider specific abnormalities in receiving and outputting information among frequency bands during integration. Here, we investigated heterogeneity in receiving and outputting information during cross-frequency integration in patients. The results showed that during cross-frequency integration, information interaction first increased and then decreased, manifesting in the heterogeneous distribution of inter-frequency nodes for receiving information. A possible explanation was that due to damage to some inter-frequency hub nodes, intra-frequency nodes gradually became new inter-frequency nodes, whereas original inter-frequency nodes gradually became new inter-frequency hub nodes. Notably, damage to the brain regions that receive information between layers was often accompanied by a strengthened ability to output information and the emergence of hub nodes for outputting information. Moreover, an important compensatory mechanism assisted in the reception of information in the cingulo-opercular and auditory networks and in the outputting of information in the visual network. This study revealed specific abnormalities in information interaction and compensatory mechanism during cross-frequency integration, providing important evidence for understanding cross-frequency integration in patients with MCI and AD.

A bibliometric and visual analysis of cognitive function in bipolar disorder from 2012 to 2022.

INTRODUCTION: Bipolar disorder (BD) is a chronic psychiatric disorder that combines hypomania or mania and depression. The study aims to investigate the research areas associated with cognitive function in bipolar disorder and identify current research hotspots and frontier areas in this field. METHODOLOGY: Publications related to cognitive function in BD from 2012 to 2022 were searched on the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and Scimago Graphica were used to conduct this bibliometric analysis. RESULTS: A total of 989 articles on cognitive function in BD were included in this review. These articles were mainly from the United States, China, Canada, Spain and the United Kingdom. Our results showed that the journal "Journal of Affective Disorders" published the most articles. Apart from "Biploar disorder" and "cognitive function", the terms "Schizophrenia", "Meta analysis", "Rating scale" were also the most frequently used keywords. The research on cognitive function in bipolar disorder primarily focused on the following aspects: subgroup, individual, validation and pathophysiology. CONCLUSIONS: The current concerns and hotspots in the filed are: "neurocognitive impairment", "subgroup", "1st degree relative", "mania", "individual" and "validation". Future research is likely to focus on the following four themes: "Studies of the bipolar disorder and cognitive subgroups", "intra-individual variability", "Validation of cognitive function tool" and "Combined with pathology or other fields".

SABRE Hyperpolarization of Exchangeable Protons in Methanol-d4 through Dynamic Covalent Bonds.

Utilizing para-hydrogen (p-H2)-induced hyperpolarization to increase the sensitivity of nuclear magnetic resonance, especially signal amplification by reversible exchange (SABRE), has been widely studied. Here, we achieved hyperpolarization of exchangeable protons in methanol-d4 by introducing dynamic covalent bonds as reversible exchange following the SABRE process. To release the hyperpolarized CD3OH, the pyridine-based ligands with aldehyde groups underwent acetal exchange between the aldehyde and hydroxyl groups of CD3OH after being first hyperpolarized by SABRE. Our mechanistic study highlights the importance of the reversible exchange of functional groups and chemical kinetics in realizing hyperpolarization of exchangeable protons in methanol-d4. Our work broadens SABRE's chemical system compatibility and possible applications.

High-Quality Reconstruction for Laplace NMR Based on Deep Learning.

Laplace nuclear magnetic resonance (NMR) exploits relaxation and diffusion phenomena to reveal information regarding molecular motions and dynamic interactions, offering chemical resolution not accessible by conventional Fourier NMR. Generally, the applicability of Laplace NMR is subject to the performance of signal processing and reconstruction algorithms involving an ill-posed inverse problem. Here, we propose a proof-of-concept of a deep-learning-based method for rapid and high-quality spectra reconstruction from Laplace NMR experimental data. This reconstruction method is performed based on training on synthetic exponentially decaying data, which avoids a vast amount of practically acquired data and makes it readily suitable for one-dimensional relaxation and diffusion measurements by commercial NMR instruments.

Analysis of Dynamic Network Reconfiguration in Adults with Attention-Deficit/Hyperactivity Disorder Based Multilayer Network.

Attention-deficit/hyperactivity disorder (ADHD) has been reported exist abnormal topology structure in the brain network. However, these studies often treated the brain as a static monolithic structure, and dynamic characteristics were ignored. Here, we investigated how the dynamic network reconfiguration in ADHD patients differs from that in healthy people. Specifically, we acquired resting-state functional magnetic resonance imaging data from a public dataset including 40 ADHD patients and 50 healthy people. A novel model of a "time-varying multilayer network" and metrics of recruitment and integration were applied to describe group differences. The results showed that the integration scores of ADHD patients were significantly lower than those of controls at every level. The recruitment scores were lower than healthy people except for the whole-brain level. It is worth noting that the subcortical network and the thalamus in ADHD patients exhibited reduced alliance preference both within and between functional networks. In addition, we also found that recruitment and integration coefficients showed a significant correlation with symptom severity in some regions. Our results demonstrate that the capability to communicate within or between some functional networks is impaired in ADHD patients. These evidences provide a new opportunity for studying the characteristics of ADHD brain networks.

Correction: Chen et al. The Total Solubility of the Co-Solubilized PAHs with Similar Structures Indicated by NMR Chemical Shift. Molecules 2021, 26, 2793.

In the original article [...].

Mechanism of the Micellar Solubilization of Curcumin by Mixed Surfactants of SDS and Brij35 via NMR Spectroscopy.

The micellar solubilization mechanism of curcumin by mixed surfactants of SDS and Brij35 was investigated at the molecular scale by NMR spectroscopy. Through the investigation of the micelle formation process, types and structures of mixed micelles and solubilization sites, the intrinsic factors influencing the solubilization capacity were revealed. For systems with αSDS = 0.5 and 0.2, the obtained molar solubilization ratios (MSRs) are consistent with the MSRideal values. However, for αSDS = 0.8, the solubilization capacity of curcumin is weakened compared to the MSRideal. Furthermore, only one single mixed SDS/Brij35 micelles are formed for αSDS = 0.5 and 0.2. However, for αSDS = 0.8, there are separate SDS-rich and Brij35-rich mixed micelles formed. In addition, NOESY spectra show that the interaction patterns of SDS and Brij35 in mixed micelles are similar for three systems, as are the solubilization sites of curcumin. Therefore, for αSDS = 0.5 and 0.2 with single mixed micelles formed, the solubility of curcumin depends only on the mixed micelle composition, which is almost equal to the surfactant molar ratio. Although curcumin is solubilized in both separate micelles at αSDS = 0.8, a less stable micelle structure may be responsible for the low solubility. This study provides new insights into the investigation and application of mixed micelle solubilization.

Deficit of Cross-Frequency Integration in Mild Cognitive Impairment and Alzheimer's Disease: A Multilayer Network Approach.

BACKGROUND: Studies at specific frequencies have shown abnormalities in brain functional networks among mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Previous studies have failed to take into account the possibility that optimal cognitive integration requires interactions between different frequency bands. PURPOSE: To study whether there is abnormal cross-frequency integration in patients' brains during disease progression. STUDY TYPE: Retrospective. POPULATION: Forty-six normal control (NC), 85 patients with MCI, and 31 patients with AD. FIELD STRENGTH/SEQUENCE: 3T. ASSESSMENT: Multilayer network models were constructed for NC, MCI, and AD, and multilayer participation coefficient (MPC) was used to study the changes of the interlayer relationship in the course of disease development. In addition, MPC and an overlapping degree were combined to classify nodes in the network, and the role of key nodes in the interlayer interaction was mainly observed. Finally, the correlation between multilayer network measures and cognitive function was investigated. STATISTICAL TESTS: Pearson chi-squared two-tailed test, one-way analysis of variance (ANOVA), nonparametric Spearman correlation coefficient r, and the false discovery rate. RESULTS: The MPC of the network decreased significantly in MCI (P < 0.05) and AD (P < 0.05). The number of intralayer nodes increased significantly (MCI [P < 0.05], AD [P < 0.05]) and the number of interlayer nodes decreased significantly. Centrality loss between frequencies of a large number of hub nodes, among which the damaged hub nodes included the left hippocampus, left precuneus, right precuneus, left posterior cingulate gyrus, left precentral gyrus, right precentral gyrus, left medial superior frontal gyrus, and right postcentral gyrus. MPC was significantly associated with memory impairment in patients (AD [Spearman's r = 0.526, P < 0.05], MCI [Spearman's r = 0.229, P < 0.05]), and these related regions included damaged hub nodes in patients. DATA CONCLUSION: In the multilayer networks of patients, there was an obvious deficit in cross-frequency integration and the hub nodes were preferentially damaged. Moreover, these vulnerable hubs are associated with patients' cognitive scores. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

A broad-range variable-temperature solid state NMR spectral and relaxation investigation of the water state in Nafion 117.

Understanding the water state in Nafion is not only crucial for operating a proton-exchange membrane (PEM)-based fuel cell, but also intimately related to the elucidation of the proton transport mechanism in a PEM. Although many studies have been published on this subject, some controversies and ambiguities remain unresolved. In this work, we design three different types of Nafion samples by substituting protons with lithium or sodium cations. We also pay special attention to the preparation of samples for carrying out broad-range variable temperature solid state NMR experiments so that no membrane dehydration occurs during the long experimental time at low temperatures. With these precautions and improvements, clear and largely straightforward information could be obtained to ensure minimal ambiguity and complexity in the interpretation of the experimental data. Our results show that about 40-60% of water remains unfrozen at -70 °C, depending on the type of the substituting cation. Both the 1H and 2H spectral and relaxation results indicate that water freezing starts from the center of the nanopores inside Nafion and increases gradually as the temperature decreases. The protons remain dissociated with sulfonate groups even at the lowest temperature we reached (-70 °C), whereas both lithium and sodium are associated with sulfonate groups at most temperatures below 0 °C. The experimental data also suggest that besides frozen and unfrozen water, there is broad distribution of water state and dynamics in Nafion as the temperature is lowered from above zero down to -70 °C. The effect of the size of the substituting cation significantly affects the properties of supercooled water by modifying the cation-water interaction and impeding the rotation of sulfonate groups. These novel results not only help us in establishing a better understanding of the water state in Nafion and its performance as a proton exchange mebrane, but also provide insights into water freezing, antifreeze and supercooling in other nanoscopic environments.

The Total Solubility of the Co-Solubilized PAHs with Similar Structures Indicated by NMR Chemical Shift.

The synergism/inhibition level, solubilization sites and the total solubility (St) of co-solubilization systems of phenanthrene, anthracene and pyrene in Tween 80 and sodium dodecyl sulfate (SDS) are studied by 1H-NMR, 2D nuclear overhauser effect spectroscopy (NOESY) and rotating frame overhauser effect spectroscopy (ROESY). In Tween 80, inhibition for phenanthrene, anthracene and pyrene is observed in most binary and ternary systems. However, in SDS, synergism is predominant. After analysis, we find that the different synergism or inhibition situation between Tween 80 and SDS is related to the different types of surfactants used and the resulting different co-solubilization mechanisms. In addition, we also find that three polycyclic aromatic hydrocarbons (PAHs) have similar solubilization sites in both Tween 80 and SDS, which are almost unchanged in co-solubilization systems. Due to the similar solubilization sites, the chemical shift changes of surfactant and PAH protons follow the same pattern in all solubilization systems, and the order of chemical shift changes is consistent with the order of changes in the St of PAHs. In this case, it is feasible to evaluate St of PAHs by chemical shift. In both Tween 80 and SDS solutions, the ternary solubilization system has relatively high St rankings. Therefore, in practical applications, a good overall solubilization effect can be expected.

Comparative neutralizing potencies of antibodies suggest conservation as well as mechanistic differences in human cytomegalovirus entry into epithelial and endothelial cells.

Antibody neutralization of cytomegalovirus (CMV) entry into diverse cell types is a key consideration for development of vaccines and immunotherapeutics. CMV entry into fibroblasts differs significantly from entry into epithelial or endothelial cells: fibroblast entry is mediated by gB and gH/gL/gO, whereas both epithelial and endothelial cell entry require an additional pentameric complex (PC) comprised of gH/gL/UL128/UL130/UL131A. Because PC-specific antibodies in CMV-seropositive human sera do not affect fibroblast entry but potently block entry into epithelial or endothelial cells, substantially higher neutralizing potencies for CMV-positive sera are observed when assayed using epithelial cells as targets than when using fibroblasts. That certain sera exhibit similar discordances between neutralizing potencies measured using epithelial vs. endothelial cells (Gerna G. et al.J Gen Virol, 89:853-865, 2008) suggested that additional mechanistic differences may also exist between epithelial and endothelial cell entry. To further explore this issue, neutralizing potencies using epithelial and endothelial cells were simultaneously determined for eight CMV-positive human sera, CMV-hyperimmune globulin, and a panel of monoclonal or anti-peptide antibodies targeting specific epitopes in gB, gH, gH/gL, or the PC. No significant differences were observed between epithelial and endothelial neutralizing potencies of epitope-specific antibodies, CMV-hyperimmune globulin, or seven of the eight human sera. However, one human serum exhibited a six-fold higher potency for neutralizing entry into epithelial cells vs. endothelial cells. These results suggest that epitopes exist that are important for epithelial entry but are less critical, or perhaps dispensable, for endothelial cell entry. Their existence should be considered when developing monoclonal antibody therapies or subunit vaccines representing limited epitopes.

Different submicellar solubilization mechanisms revealed by 1H NMR and 2D diffusion ordered spectroscopy (DOSY).

Different submicellar solubilization mechanisms of two systems, Triton X-100 (TX-100)/tetradecane and sodium dodecyl sulfate (SDS)/butyl methacrylate, are revealed on the molecular scale by 1H NMR spectroscopy and 2D diffusion ordered spectroscopy (DOSY). It is evident that the apparent solubilities of both tetradecane and butyl methacrylate are enhanced, even at much lower surfactant concentrations than the CMCs. Solubilized solutes also contribute to the early formation of surfactant micelles. In general, the molar solubilization ratios (MSRs) of both solutes linearly increase as the surfactant concentrations increase. However, variations in MSRs of the two systems are different below and above the CMC, which is probably related to the different solubilization mechanisms. For TX-100/tetradecane, as the TX-100 concentration increases, the tetradecane resonance in the independent state transforms into that of the aggregated state and the corresponding evolution of diffusions is shown in the 2D DOSY spectra. These results demonstrate that below the CMC, tetradecane is first solubilized in TX-100 solutions, and then solubilized in TX-100 micelles above the CMC. For SDS/butyl methacrylate, the appearance of oligomeric SDS resonances below the CMC indicates that butyl methacrylate is partially solubilized in SDS oligomers. Then, when the CMC is reached, the dominant, monomeric SDS molecules aggregate into oligomers, and the similar diffusivity trend of butyl methacrylate with that of SDS indicates that a proportion of butyl methacrylate molecules are solubilized in it. Finally, the fusion of SDS resonances in the two states and the tendency of co-diffusion of SDS and butyl methacrylate indicate that all the SDS molecules gradually aggregate into micelles, and almost all the butyl methacrylate molecules are solubilized in them. In conclusion, above the CMCs, the solubilization manners of these two systems are similar. However, they are different below CMCs. The solubilization of tetradecane by TX-100 is driven by the intermolecular hydrophobic interaction, i.e., molecular-pair formation. However, the polar interaction between functional groups of butyl methacrylate and the polar head of SDS contributes to the solubilization of butyl methacrylate. The different submicellar solubilization mechanisms are mainly caused by the different properties of solutes and surfactants, which also results in different MSRs and solubilization sites in the micelles.

Impact of Antibodies and Strain Polymorphisms on Cytomegalovirus Entry and Spread in Fibroblasts and Epithelial Cells.

Cytomegalovirus (CMV) entry into fibroblasts differs from entry into epithelial cells. CMV also spreads cell to cell and can induce syncytia. To gain insights into these processes, 27 antibodies targeting epitopes in CMV virion glycoprotein complexes, including glycoprotein B (gB), gH/gL, and the pentamer, were evaluated for their effects on viral entry and spread. No antibodies inhibited CMV spread in fibroblasts, including those with potent neutralizing activity against fibroblast entry, while all antibodies that neutralized epithelial cell entry also inhibited spread in epithelial cells and a correlation existed between the potencies of these two activities. This suggests that exposure of virions to the cell culture medium is obligatory during spread in epithelial cells but not in fibroblasts. In fibroblasts, the formation of syncytiumlike structures was impaired not only by antibodies to gB or gH/gL but also by antibodies to the pentamer, suggesting a potential role for the pentamer in promoting fibroblast fusion. Four antibodies reacted with linear epitopes near the N terminus of gH, exhibited strain specificity, and neutralized both epithelial cell and fibroblast entry. Five other antibodies recognized conformational epitopes in gH/gL and neutralized both fibroblast and epithelial cell entry. That these antibodies were strain specific for neutralizing fibroblast but not epithelial cell entry suggests that polymorphisms external to certain gH/gL epitopes may influence antibody neutralization during fibroblast but not epithelial cell entry. These findings may have implications for elucidating the mechanisms of CMV entry, spread, and antibody evasion and may assist in determining which antibodies may be most efficacious following active immunization or passive administration.IMPORTANCE Cytomegalovirus (CMV) is a significant cause of birth defects among newborns infected in utero and morbidity and mortality in transplant and AIDS patients. Monoclonal antibodies and vaccines targeting humoral responses are under development for prophylactic or therapeutic use. The findings reported here (i) confirm that cell-to-cell spread of CMV is sensitive to antibody inhibition in epithelial cells but not fibroblasts, (ii) demonstrate that antibodies can restrict the formation in vitro of syncytiumlike structures that resemble syncytial cytomegalic cells that are associated with CMV disease in vivo, and (iii) reveal that neutralization of CMV by antibodies to certain epitopes in gH or gH/gL is both strain and cell type dependent and can be governed by polymorphisms in sequences external to the epitopes. These findings serve to elucidate the mechanisms of CMV entry, spread, and antibody evasion and may have important implications for the development of CMV vaccines and immunotherapeutics.

A high-affinity native human antibody neutralizes human cytomegalovirus infection of diverse cell types.

Human cytomegalovirus (HCMV) is the most common infection causing poor outcomes among transplant recipients. Maternal infection and transplacental transmission are major causes of permanent birth defects. Although no active vaccines to prevent HCMV infection have been approved, passive immunization with HCMV-specific immunoglobulin has shown promise in the treatment of both transplant and congenital indications. Antibodies targeting the viral glycoprotein B (gB) surface protein are known to neutralize HCMV infectivity, with high-affinity binding being a desirable trait, both to compete with low-affinity antibodies that promote the transmission of virus across the placenta and to displace nonneutralizing antibodies binding nearby epitopes. Using a miniaturized screening technology to characterize secreted IgG from single human B lymphocytes, 30 antibodies directed against gB were previously cloned. The most potent clone, TRL345, is described here. Its measured affinity was 1 pM for the highly conserved site I of the AD-2 epitope of gB. Strain-independent neutralization was confirmed for 15 primary HCMV clinical isolates. TRL345 prevented HCMV infection of placental fibroblasts, smooth muscle cells, endothelial cells, and epithelial cells, and it inhibited postinfection HCMV spread in epithelial cells. The potential utility for preventing congenital transmission is supported by the blockage of HCMV infection of placental cell types central to virus transmission to the fetus, including differentiating cytotrophoblasts, trophoblast progenitor cells, and placental fibroblasts. Further, TRL345 was effective at controlling an ex vivo infection of human placental anchoring villi. TRL345 has been utilized on a commercial scale and is a candidate for clinical evaluation.

CH3NH3PbI(3-x)Cl(x) films with coverage approaching 100% and with highly oriented crystal domains for reproducible and efficient planar heterojunction perovskite solar cells.

Depositing pinhole-free perovskite films is of vital importance for achieving high performance perovskite solar cells, especially in a planar heterojunction device. Here, perovskite films with coverage approaching 100% and with highly oriented crystal domains were obtained by carefully controlling the annealing temperature and duration. Perovskite solar cells with an average efficiency of 12% and a maximum efficiency of 15.17% were achieved in a planar heterojunction structure. Comprehensive characterization and analysis showed that appropriate annealing temperature and duration allowed the perovskite crystals to grow slowly, resulting in highly oriented crystal domains without any internal voids or pinholes. The anisotropic transport properties of perovskite crystals ensure efficient electron and hole transport to their corresponding electrodes.

Aberrant Functional Connectivity in Core-Periphery Structure Based on WSBM in ADHD.

OBJECTIVE: Brain network studies have revealed that the community structure of ADHD is altered. However, these studies have only focused on modular community structure, ignoring the core-periphery community structure. METHOD: This paper employed the weighted stochastic block model to divide the functional connectivity (FC) into 10 communities. And we adopted core score to define the core-periphery structure of FC. Finally, connectivity strength (CS) and disruption index (DI) were used to evaluate the changes of core-periphery structure in ADHD. RESULTS: The core community of visual network showed reduced CS and a positive value of DI, while the CS of periphery community was enhanced. In addition, the interaction between core communities (involving the sensorimotor and visual network) and periphery community of attention network showed increased CS and a negative valve of DI. CONCLUSION: Anomalies in core-periphery community structure provide a new perspective for understanding the community structure of ADHD.