Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Collagen I protects human keratinocytes HaCaT against UVB injury via restoring PINK1/parkin-mediated mitophagy.

Collagen I is a major component of extracellular matrix in human skin, and is also widely used in a variety of skin-care products. In this study, we investigated the modulatory roles of collagen I on human immortalized keratinocytes HaCaT, especially when cells were irradiated with UVB. Interestingly, the cells grown on plates coated by molecular collagen I, but not fibrillar collagen I, acquired certain resistance against UVB damages, as shown by increased survival and reduced apoptosis. The accumulation of dysfunctional mitochondria in UVB-treated cells was attenuated by molecular collagen I-coating. Interestingly, molecular collagen I rescued the loss of mitochondrial biogenesis in cells treated with UVB. Loss of PINK1/parkin-mediated mitophagy was dominant for the accumulation of dysfunctional mitochondria after UVB irradiation. Of note, cells cultured on molecular collagen I-precoated plates exhibited reserved mitophagy after UVB irradiation, as reflected by the enhanced protein level of PINK1/parkin, increased mitochondrial ubiquitin and the co-localization of lysosomes and mitochondria. Moreover, in UVB-treated cells, inhibiting mitophagy by Cyclosporin A, or by silencing PINK1 or parkin, disturbed the resolution of mitochondrial stress and reduced the protective effect of molecular collagen I, indicating that mitophagy is pivotal for the protection of collagen I against UVB damage in keratinocytes HaCaT. Collectively, this study reveals an unexpected protective role of collagen I, which facilitates mitophagy to rescue cells under UVB irradiation, providing a new direction for clinical application of collagen products.

Janus Flexible Device with Microcone Channels for Sampling and Analysis of Biological Microfluidics.

Controlling the spontaneous directional transport of droplets plays an important role in the application of microchemical reactions and microdroplet detection. Although the relevant technologies have been widely studied, the existing spontaneous droplet transport strategies still face problems of complex structure, single function, and poor flexibility. Inspired by the spontaneous droplet transport strategy in nature, an asymmetric wettability surface with microcone channels (AWS-MC) is prepared on a flexible fabric by combining surface modification and femtosecond laser manufacturing technology. On this surface, the capillary force and Laplace pressure induced by the wettability gradient and the geometric structure gradient drive the droplet transport from the hydrophobic surface to the hydrophilic surface. Notably, droplets in adjacent hydrophilic regions do not exchange substances even if the gap in the hydrophilic region is only 1 mm, which provides an ideal platform for numerous detections by a single drop. The droplet transport strategy does not require external energy and can adapt to the manipulation of various droplet types. Application of this surface in the blood of organisms is demonstrated. This work provides an effective method for microdroplet-directed self-transport and microdroplet detection.

Impaired mitophagy causes mitochondrial DNA leakage and STING activation in ultraviolet B-irradiated human keratinocytes HaCaT.

Ultraviolet B (UVB) irradiation causes skin damages. In this study, we focus on the involvement of mitochondrial disorders in UVB injury. Surprisingly, UVB irradiation increases the amounts of mitochondria in human immortalized keratinocytes HaCaT. However, further analysis shows that ATP levels decreased by UVB treatment in accordance with the collapse of mitochondrial membrane potential (MMP), suggesting an accumulation of dysfunctional mitochondria in UVB-irradiated HaCaT cells. Mitophagy, mainly mediated by PINK1 and parkin, is critical for the elimination of damaged mitochondria. Western blot results show that the levels of both PINK1 and parkin are decreased in UVB-irradiated cells, indicating the impairment of mitophagy. Silencing the expression of PINK1 or parkin by transfection of siRNA shows essentially the same damage to the cells as UVB irradiation does, including increased mitochondrial amount, decreased MMP and ATP production, and enhanced apoptosis, evidencing that repression of PINK1/parkin-mediated mitophagy plays a primary cause of UVB-caused cells damages. We previously found that HaCaT cells exposed to UVB showed activation of the cGAS-STING pathway and apoptosis. Here, silencing PINK1 or parkin also increases the protein levels of cGAS and STING, facilitates nuclear accumulation of NF-κB, and promotes the transcription of IFNß, suggesting for the activation of STING pathway. Mitophagy impairment either by UVB-irradiation or by PINK1/parkin silencing initiates caspase-3-mediated apoptosis, as shown by the activation of caspase-3 and cleavage of PARP, as well as the increase of Hoechst-positive stained cells and Annexin V-positive cells. Further studies find that Bax-mediated permeabilization of mitochondrial membrane is critical for cell apoptosis, as well as the cytosolic leakage of mtDNA in UVB-treated cells, which results in cGAS-STING activation, and these processes are negatively-regulated by PINK1/parkin-mediated mitophagy. This study reveals the involvement of dysfunctional mitochondria due to impaired mitophagy in the damaging effect of UVB irradiation on HaCaT cells. Restoring the mitophagy has the potential to be developed as a new strategy to protect skin from UVB damages.

Increased mitochondrial fission induces NLRP3/cGAS-STING mediated pro-inflammatory pathways and apoptosis in UVB-irradiated immortalized human keratinocyte HaCaT cells.

Ultraviolet B (UVB) irradiation causes skin inflammation and apoptosis. Mitochondria are highly dynamic and undergo constant fusion and fission that are essential for maintaining physiological functions of cells. Although dysfunction of mitochondria has been implicated in skin damages, little is known about the roles of mitochondrial dynamics in these processes. UVB irradiation increases abnormal mitochondrial content but decreases mitochondrial volume in immortalized human keratinocyte HaCaT cells. UVB irradiation resulted in marked upregulation of mitochondrial fission protein dynamin-related protein 1 (DRP1) and downregulation of mitochondrial outer membrane fusion proteins 1 and 2 (MFN1 and MFN2) in HaCaT cells. Mitochondrial dynamics was discovered to be crucial for NLRP3 inflammasome and cGAS-STING pathway activation, as well as the induction of apoptosis. Inhibition of mitochondrial fission by treatments with a DRP1 inhibitor, mdivi-1, or with DRP1-targeted siRNA, efficiently prevented UVB-induced NLRP3/cGAS-STING mediated pro-inflammatory pathways or apoptosis in the HaCaT cells, whereas inhibition of mitochondrial fusion with MFN1and 2 siRNA increased these pro-inflammatory pathways or apoptosis. The enhanced mitochondrial fission and reduced fusion caused the up-regulation of reactive oxygen species (ROS). Application of an antioxidant, N-acetyl-l-cysteine (NAC), which scavenges excessive ROS, attenuated inflammatory responses through suppressing NLRP3 inflammasome and cGAS-STING pathway activation, and rescued cells from apoptosis caused by UVB-irradiation. Together, our findings revealed the regulation of NLRP3/cGAS-STING inflammatory pathways and apoptosis by mitochondrial fission/fusion dynamics in UVB-irradiated HaCaT cells, providing a new strategy for the therapy of UVB skin injury.

Heterogeneous decision-making dynamics of threshold-switching agents on complex networks.

In the classical two-player decision-making scenario, individuals may have different tendencies to take a certain action, given that there exists a sufficient number of neighbors adopting a particular option. This is ubiquitous in many real-life contexts including traffic congestion, crowd evacuation, and minimal vertex cover problem. Under best-response dynamics, we investigate the decision-making behaviors of heterogeneous agents on complex networks. Results of the networked games are twofold: for networks of uniform degree distribution (e.g., the lattice) and fraction of the strategy is of a linear function of the threshold setting. Moreover, the equilibrium analysis is provided and the relationship between the equilibrium dynamics and the change of the threshold value is given quantitatively. Next, if the games are played on networks with non-uniform degree distribution (e.g., random regular and scale-free networks), influence of the threshold-switching will be weakened. Robust experiments indicate that it is not the value of the average degree, but the degree distribution that influences how the strategy evolves affected by the threshold settings. Our result shows that the decision-making behaviors can be effectively manipulated by tuning the parameters in the utility function (i.e., thresholds) of some agents for more regular network structures.

Evolutionary dynamics of N-player sender-receiver game in networks with community structure.

Network typology largely affects the evolutionary dynamics of collective behaviors in many real-world complex systems. As a conventional transmission model, the sender-receiver game paves the way to explore the evolution of honest signals between senders and receivers. In practice, the utilities of an agent often depend not only on pairwise interactions, but also on the group influence of players around them, and thus there is an urgent need for deeper theoretical modeling and investigations on individuals' non-pairwise interactions. Considering the underlying evolutionary game dynamics and multiple community network structures, we explore the evolution of honest behaviors by extending the sender-receiver game to multiple communities. With the new dynamical model of the multi-community system, we perform a stability analysis of the system equilibrium state. Our results reveal the condition to promote the evolution of honest behaviors and provide an effective method for enhancing collaboration behaviors in distributed complex systems. Current results help us to deeply understand how collective decision-making behaviors evolve, influenced by the spread of true information and misinformation in large dynamic systems.

Eltrombopag Inhibits Metastasis in Breast Carcinoma by Targeting HuR Protein.

Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as Snail, Cox-2, and Vegf-c. However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.

Comparative Transcriptome Analysis between Resistant and Susceptible Pakchoi Cultivars in Response to Downy Mildew.

Downy mildew caused by the obligate parasite Hyaloperonospora brassicae is a devastating disease for Brassica species. Infection of Hyaloperonospora brassicae often leads to yellow spots on leaves, which significantly impacts quality and yield of pakchoi. In the present study, we conducted a comparative transcriptome between the resistant and susceptible pakchoi cultivars in response to Hyaloperonospora brassicae infection. A total of 1073 disease-resistance-related differentially expressed genes were identified using a Venn diagram. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly involved in plant-pathogen interaction, plant hormone signal transduction, and other photosynthesis-related metabolic processes. Analysis of the phytohormone content revealed that salicylic acid increased significantly in the resistant material after inoculation with Hyaloperonospora brassicae, whereas the contents of jasmonic acid, abscisic acid, and 1-aminocyclopropane-1-carboxylic acid decreased. Exogenous salicylic acid treatment also significantly upregulated Hyaloperonospora brassicae-induced genes, which further confirmed a crucial role of salicylic acid during pakchoi defense against Hyaloperonospora brassicae. Based on these findings, we suggest that the salicylic-acid-mediated signal transduction contributes to the resistance of pakchoi to downy mildew, and PAL1, ICS1, NPR1, PR1, PR5, WRKY70, WRKY33, CML43, CNGC9, and CDPK15 were involved in this responsive process. Our findings evidently contribute to revealing the molecular mechanism of pakchoi defense against Hyaloperonospora brassicae.

Changes in Diversity and Composition of Rhizosphere Bacterial and Fungal Community between Resistant and Susceptible Pakchoi under Plasmodiophora brassicae.

Plasmodiophora brassicae (P. brassicae) is a soil-born pathogen worldwide and can infect most cruciferous plants, which causes great yield decline and economic losses. It is not well known how microbial diversity and community composition change during P. brassicae infecting plant roots. Here, we employed a resistant and a susceptible pakchoi cultivar with and without inoculation with P. brassicae to analyze bacterial and fungal diversity using 16S rRNA V3-V4 and ITS_V1 regions, respectively. 16S rRNA V3-V4 and ITS_V1 regions were amplified and sequenced separately. Results revealed that both fungal and bacterial diversity increased, and composition was changed in the rhizosphere soil of the susceptible pakchoi compared with the resistant cultivar. In the four groups of R_mock, S_mock, R_10d, and S_10d, the most relatively abundant bacterium and fungus was Proteobacteria, accounting for 61.92%, 58.17%, 48.64%, and 50.00%, respectively, and Ascomycota, accounting for 75.11%, 63.69%, 72.10%, and 90.31%, respectively. A total of 9488 and 11,914 bacteria were observed uniquely in the rhizosphere soil of resistant and susceptible pakchoi, respectively, while only 80 and 103 fungi were observed uniquely in the correlated soil. LefSe analysis showed that 107 and 49 differentially abundant taxa were observed in bacteria and fungi. Overall, we concluded that different pakchoi cultivars affect microbial diversity and community composition, and microorganisms prefer to gather around the rhizosphere of susceptible pakchoi. These findings provide a new insight into plant-microorganism interactions.

Integrated Transcriptome and Proteome Analysis Revealed the Regulatory Mechanism of Hypocotyl Elongation in Pakchoi.

Hypocotyl length is a critical determinant for the efficiency of mechanical harvesting in pakchoi production, but the knowledge on the molecular regulation of hypocotyl growth is very limited. Here, we report a spontaneous mutant of pakchoi, lhy7.1, and identified its characteristics. We found that it has an elongated hypocotyl phenotype compared to the wild type caused by the longitudinal growth of hypocotyl cells. Different light quality treatments, transcriptome, and proteomic analyses were performed to reveal the molecular mechanisms of hypocotyl elongation. The data showed that the hypocotyl length of lhy7.1 was significantly longer than that of WT under red, blue, and white lights but there was no significant difference under dark conditions. Furthermore, we used transcriptome and label-free proteome analyses to investigate differences in gene and protein expression levels between lhy7.1 and WT. At the transcript level, 4568 differentially expressed genes (DEGs) were identified, which were mainly enriched in "plant hormone signal transduction", "photosynthesis", "photosynthesis-antenna proteins", and "carbon fixation in photosynthetic organisms" pathways. At the protein level, 1007 differentially expressed proteins (DEPs) were identified and were mainly enriched in photosynthesis-related pathways. The comprehensive transcriptome and proteome analyses revealed a regulatory network of hypocotyl elongation involving plant hormone signal transduction and photosynthesis-related pathways. The findings of this study help elucidate the regulatory mechanisms of hypocotyl elongation in lhy7.1.

Characterization of a novel marine microbial uricase from Priestia flexa and evaluation of the effects of CMCS conjugation on its enzymatic properties.

A novel uricase producing marine bacterium Priestia flexa alkaAU was isolated and identified. The 16S rDNA and the uricase coding gene were sequenced, analyzed and submitted to GenBank. The uricase from Priestia flexa alkaAU (PFU) was purified, determined to be 58.87 kDa, and conjugated with carboxymethyl chitosan (CMCS) by ionic gelation. CMCS conjugation had no effect on the optimum pH of PFU but decreased the optimum temperature by 10 °C. CMCS conjugation increased the specific activity of PFU by 53% at the human body temperature (37 °C) and small intestine's pH (pH 6.8). Uricase thermostabilizing ability of CMCS was significant in the range of 37-80 °C but not at lower temperatures. For improvement of the pH stability of PFU, CMCS was more effective at pHs 3-5 than pHs 6-11. CMCS increased the half-life of PFU against artificial intestinal fluid by 1.5 folds, which demonstrated the potential capability of CMCS-PFU for oral administration.

Silibinin relieves UVB-induced apoptosis of human skin cells by inhibiting the YAP-p73 pathway.

Excessive exposure to UVB induces skin diseases. Silibinin, a flavonolignan used for treating liver diseases, is found to be effective against UVB-caused skin epidermal and dermal cell damage. In this study we investigated the molecular mechanisms underlying. Human nonmalignant immortalized keratinocyte HaCaT cells and neonatal human foreskin fibroblasts HFFs were exposed to UVB irradiation. We showed that pre-treatment with silibinin dose-dependently decreased UVB-induced apoptosis of HaCaT cells. Furthermore, we showed that silibinin treatment inhibited nuclear translocation of YAP after UVB irradiation. Molecular docking analysis and DARTS assay confirmed the direct interaction of silibinin with YAP. Silencing YAP by siRNA had no influence on the survival of HaCaT cells, whereas inhibiting classical YAP-TEAD signaling pathway by siRNA targeting TEAD1 or its pharmaceutical inhibitor verteporfin further augmented UVB-induced apoptosis, suggesting that YAP-TEAD pathway was prosurvival, which did not participate in the protective effect of silibinin. We then explored the pro-apoptotic YAP-p73 pathway. p73 was upregulated in UVB-irradiated cells, but reduced by silibinin cotreatment. The mRNA and protein levels of p73 target genes (PML, p21 and Bax) were all increased by UVB but decreased by silibinin co-treatment. Inhibiting p73 by using siRNA reduced UVB-induced apoptosis, suggesting that downregulation of p73 was responsible for the cytoprotective effect of silibinin. In HFFs, the upregulated YAP-p73 pathway by UVB irradiation was also suppressed by silibinin. Collectively, YAP-p73 pathway is a major cause of the death of UVB-exposed epidermal HaCaT cells and dermal HFFs. Silibinin directly inhibits YAP-p73 pathway, exerting the protective action on UVB-irradiated skin cells.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

BACKGROUND AND AIMS: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). METHODS: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. RESULTS: In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005-1.023), baseline ALT (HR = 1.014, 95% CI: 1.003-1.024), haemoglobin (HR = 1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003-1.056), baseline AST (HR = 1.036, 95% CI: 1.010-1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304-11.625) and active drinking (HR = 3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. CONCLUSION: Elevation of ALT of ≥3 × ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

Pseudoephedrine and its derivatives antagonize wild and mutated severe acute respiratory syndrome-CoV-2 viruses through blocking virus invasion and antiinflammatory effect.

The coronavirus disease 2019 has infected over 150 million people worldwide and led to over 3 million deaths. Severe acute respiratory syndrome (SARS)-CoV-2 lineages B.1.1.7, B.1.617, B.1.351, and P.1 were reported to have higher infection rates than that of wild one. These mutations were noticed to happen in the receptor-binding domain of spike protein (S-RBD), especially mutations N501Y, E484Q, E484K, K417N, K417T, and L452R. Currently, there is still no specific medicine against the virus; moreover, cytokine storm is also a dangerous factor for severe infected patients. In this study, potential S-RBD-targeted active monomers from traditional Chinese medicine Ephedra sinica Stapf (ephedra) were discovered by virtual screening. NanoBiT assay was performed to confirm blocking activities of the screened compounds against the interaction between SARS-CoV-2 S-RBD and angiotensin-converting enzyme 2 (ACE2). We further analyzed the blocking effect of the active compounds on the interactions of mutated S-RBD and ACE2 by computational studies. Moreover, antiinflammatory activities were evaluated using qRT-PCR, enzyme-linked immune sorbent assay, and Western blot analysis. As a result, pseudoephedrine (MHJ-17) and its derivative (MHJ-11) were found as efficient inhibitors disrupting the interactions between ACE2 and both wild and mutated S-RBDs. In addition, they also have antiinflammatory activities, which can be potential drug candidates or lead compounds for further study.

Target Identification with Improved 2D-VMD for Carrier-Free UWB Radar.

In recent years, the interest in radar automatic target recognition (RATR) based on the carrier-free ultra-wideband (UWB) radar has been increasing. Compared with narrow-band and other bandwidth radars, the echo signal of the carrier-free UWB radar includes more comprehensive and detailed information with respect to the targeted object. In this paper, we first utilized 3ds Max to acquire accurate geometric models and applied a time-domain integral equation (TDIE) for echo signal acquisition under the condition that the transmitted signals had an extremely short duration period. By comparing the simulated waveform with the actual one, the accuracy of the electromagnetic modeling is verified. Furthermore, given that the actual environment is full of noise and clutter, we propose an improved two-dimensional variational mode decomposition (2D-IVMD), and an algorithm is proposed to eliminate noise and extract edge features preliminarily, which lays a foundation for further in-depth feature extraction. Then, the deep conventional neural network (DCNN) is introduced for the final recognition. The results show that the proposed methods achieve promising classification performance under the condition of low signal-to-noise ratio (SNR) values.

Decoding and mapping task states of the human brain via deep learning.

Support vector machine (SVM)-based multivariate pattern analysis (MVPA) has delivered promising performance in decoding specific task states based on functional magnetic resonance imaging (fMRI) of the human brain. Conventionally, the SVM-MVPA requires careful feature selection/extraction according to expert knowledge. In this study, we propose a deep neural network (DNN) for directly decoding multiple brain task states from fMRI signals of the brain without any burden for feature handcrafts. We trained and tested the DNN classifier using task fMRI data from the Human Connectome Project's S1200 dataset (N = 1,034). In tests to verify its performance, the proposed classification method identified seven tasks with an average accuracy of 93.7%. We also showed the general applicability of the DNN for transfer learning to small datasets (N = 43), a situation encountered in typical neuroscience research. The proposed method achieved an average accuracy of 89.0 and 94.7% on a working memory task and a motor classification task, respectively, higher than the accuracy of 69.2 and 68.6% obtained by the SVM-MVPA. A network visualization analysis showed that the DNN automatically detected features from areas of the brain related to each task. Without incurring the burden of handcrafting the features, the proposed deep decoding method can classify brain task states highly accurately, and is a powerful tool for fMRI researchers.

Direct Visualization of Ambipolar Mott Transition in Cuprate CuO_{2} Planes.

Identifying the essence of doped Mott insulators is one of the major outstanding problems in condensed matter physics and the key to understanding the high-temperature superconductivity in cuprates. We report real space visualization of Mott insulator-metal transition in Sr_{1-x}La_{x}CuO_{2+y} cuprate films that cover both the electron- and hole-doped regimes. Tunneling conductance measurements directly on the copper-oxide (CuO_{2}) planes reveal a systematic shift in the Fermi level, while the fundamental Mott-Hubbard band structure remains unchanged. This is further demonstrated by exploring the atomic-scale electronic response of CuO_{2} to substitutional dopants and intrinsic defects in a sister compound Sr_{0.92}Nd_{0.08}CuO_{2}. The results may be better explained in the framework of self-modulation doping, similar to that in semiconductor heterostructures, and form a basis for developing any microscopic theories for cuprate superconductivity.

Structural and functional abnormalities of vision-related brain regions in cirrhotic patients: a MRI study.

PURPOSE: Previous studies have focused on global cerebral alterations observed in cirrhosis. However, little was known about the specific abnormalities of vision-related brain regions in cirrhotic patients. In this study, we sought to explore neurological alterations of vision-related regions by measuring brain resting-state network connectivity, based on the structural investigation in cirrhotic patients without clinical sign of hepatic encephalopathy (HE). METHODS: Structural and functional magnetic resonance image (MRI) data were collected from 20 hepatitis B virus (HBV)-related cirrhotic patients without clinical sign of HE and from 20 healthy controls (HC). Voxel-based morphometric (VBM) analysis and brain functional network analysis were performed to detect abnormalities in cerebral structure and function. RESULTS: Cirrhotic patients showed regions with the most significant gray matter reduction primarily in vision-related brain regions, including the bilateral lingual gyri, left putamen, right fusiform gyrus, and right calcarine gyrus, and other significant gray matter reductions were distributed in bilateral hippocampus. Based on structural investigation focused on vision-related regions, brain functional network analysis revealed decreased functional connectivity between brain functional networks within vision-related regions (primary visual network (PVN), higher visual network (HVN), visuospatial network (VSN)) in the patient group compared with HC group. CONCLUSION: These results indicate that structural and functional impairment were evident in the vision-related brain regions in cirrhotic patients without clinical sign of hepatic encephalopathy. The physiopathology and clinical relevance of these changes could not be ascertained from the present study, which provided a basis for further evolution of the disease.

Superconductor-Insulator Transitions in Exfoliated Bi2Sr2CaCu2O8+δ Flakes.

We realize superconductor-insulator transitions (SIT) in mechanically exfoliated Bi2Sr2CaCu2O8+δ (BSCCO) flakes and address simultaneously their transport properties as well as the evolution of density of states. Back-gating via the solid ion conductor (SIC) engenders a SIT in BSCCO due to the modulation of carrier density by intercalated lithium ions. Scaling analysis indicates that the SIT follows the theoretical description of a two-dimensional quantum phase transition (2D-QPT). We further carry out tunneling spectroscopy in graphite(G)/BSCCO heterojunctions. We observe V-shaped gaps in the critical regime of the SIT. The density of states in BSCCO gets symmetrically suppressed by further going into the insulating regime. Our technique of combining solid state gating with tunneling spectroscopy can be easily applied to the study of other two-dimensional materials.