In Situ Growth of Wafer-Scale Patterned Graphene and Fabrication of Optoelectronic Artificial Synaptic Device Array Based on Graphene/n-AlGaN Heterojunction for Visual Learning.

The unique optical and electrical properties of graphene-based heterojunctions make them significant for artificial synaptic devices, promoting the advancement of biomimetic vision systems. However, mass production and integration of device arrays are necessary for visual imaging, which is still challenging due to the difficulty in direct growth of wafer-scale graphene patterns. Here, a novel strategy is proposed using photosensitive polymer as a solid carbon source for in situ growth of patterned graphene on diverse substrates. The growth mechanism during high-temperature annealing is elucidated, leading to wafer-scale graphene patterns with exceptional uniformity, ideal crystalline quality, and precise control over layer number by eliminating the release of volatile from oxygen-containing resin. The growth strategy enables the fabrication of two-inch optoelectronic artificial synaptic device array based on graphene/n-AlGaN heterojunction, which emulates key functionalities of biological synapses, including short-term plasticity, long-term plasticity, and spike-rate-dependent plasticity. Moreover, the mimicry of visual learning in the human brain is attributed to the regulation of excitatory and inhibitory post-synapse currents, following a learning rule that prioritizes initial recognition before memory formation. The duration of long-term memory reaches 10 min. The in situ growth strategy for patterned graphene represents the novelty for fabricating fundamental hardware of an artificial neuromorphic system.

Highly reflective Ni/Pt/Al p-electrode for improving the efficiency of an AlGaN-based deep ultraviolet light-emitting diode.

In this work, we propose a highly reflective Ni/Pt/Al p-electrode for AlGaN-based deep ultraviolet (DUV) light-emitting diodes (LEDs) with a wavelength of 276 nm. AlGaN-based DUV LEDs with traditional Al-based reflectivity electrodes suffer from device degradation and wall-plug efficiency (WPE) droop due to the Al diffusion during electrode annealing. By inserting a Pt layer between the Ni contact layer and the Al reflective layer, the contact characteristics of the p-electrode can be optimized by blocking the diffusion of the O and Al atoms, maintaining a high reflectivity of over 80% near 280 nm. Compared to the AlGaN-based DUV LEDs with Ni/Au traditional p-electrodes and Ni/Al traditional reflective p-electrodes, the WPE of the LED with a highly reflective Ni/Pt/Al p-electrode is improved by 10.3% and 30.5%, respectively. Besides, compared to the other novel reflective p-electrodes using multiple annealing or evaporation processes reported for the AlGaN-based DUV LEDs, we provide a new, to the best of our knowledge, optimization method for single evaporation and annealing p-type reflective electrodes, featured with a simpler and more convenient process flow.

Heterojunction polarization enhancement and shielding for AlGaN-based solar-blind ultraviolet avalanche detectors.

AlGaN-based solar-blind ultraviolet avalanche detectors have huge potentials in the fields of corona discharge monitoring, biological imaging, etc. Here, we study the impact of the heterojunction polarization-related effects on the AlGaN-based solar-blind ultraviolet avalanche detectors. Our work confirms that the polarization heterojunction is beneficial to reducing avalanche bias and lifting avalanche gain by improving the electric field in the depletion region, while the polarization-induced fixed charges will lead to a redistribution of the electrons, in turn shielding the charges and weakening the electric field enhancement effect. This shielding effect will need external bias to eliminate, and that is why the polarization heterojunction cannot work at relatively low bias but has an enhancement effect at high bias. Controlling the doping level between the hetero-interface can affect the shielding effect. An unintentionally doped polarization heterojunction can effectively reduce the shielding effect, thus reducing the avalanche bias. The conclusions also hold true for the negative polarization regime. We believe our findings can provide some useful insights for the design of the AlGaN-based solar-blind ultraviolet detectors.

Does Electroencephalography Seizure Duration Account for an Adequate Treatment of Magnetic Seizure Therapy for Schizophrenia?

OBJECTIVES: A seizure lasting >15 s has been considered to indicate treatment for magnetic seizure therapy (MST), a modification of electroconvulsive therapy (ECT), without much validation. This study aimed to investigate whether this seizure duration was suitable for the treatment of schizophrenia. METHODS: Altogether, 34 and 33 in-patients with schizophrenia received 10 sessions of MST and ECT, respectively. Clinical symptoms were assessed using the Positive and Negative Symptom Scale at baseline and at the 4-week follow-up. Electroencephalogram (EEG) was monitored during each MST or ECT treatment using bifrontal electrodes. RESULTS: The proportion of participants who achieved the 15-second threshold was only 28.6% in the MST group, with a significant difference between responders and nonresponders. For patients receiving MST, the average EEG seizure duration correlated with the percentage of Positive and Negative Symptom Scale reduction (t(32) = 2.51, P = 0.017, uncorrected; t(32) = 2.00, P = 0.055, corrected with clinical characteristics). The average EEG seizure duration predicted the clinical response at a trend level (Z = 1.76, P = 0.078) with an optimal cutoff of 11.3 seconds. All patients in the ECT group achieved the 15-second threshold. However, their average EEG seizure duration was uncorrelated with clinical improvement. CONCLUSIONS: The duration of EEG seizures may be associated with the antipsychotic effects of MST. This association may have been influenced by various clinical and technical factors. More research is needed to define the specific criteria for adequate MST in schizophrenia in order to achieve personalized dosing.

Predictors of Electroconvulsive Therapy Outcome in Major Depressive Disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective therapy for major depressive disorder (MDD) patients. However, few clinical predictors are available to predict the treatment outcome. This study aimed to characterize the response trajectories of MDD patients undergoing ECT treatment and to identify potential clinical and demographic predictors for clinical improvement. METHODS: We performed a secondary analysis on data from a multicenter, randomized, blinded, controlled trial with 3 ECT modalities (bifrontal, bitemporal, unilateral). The sample consisted of 239 patients whose demographic and clinical characteristics were investigated as predictors of ECT outcomes. RESULTS: The results of growth mixture modeling suggested there were 3 groups of MDD patients: a non-remit group (n = 17, 7.11%), a slow-response group (n = 182, 76.15%), and a rapid-response group (n = 40, 16.74%). Significant differences in age, education years, treatment protocol, types of medication used, Hamilton Depression Scale, Hamilton Anxiety Scale score, Mini-Mental State Examination score, and Clinical Global Impression score at baseline were observed across the groups. CONCLUSIONS: MDD patients exhibited distinct and clinically relevant response trajectories to ECT. The MDD patients with more severe depression at baseline are associated with a rapid response trajectory. In contrast, MDD patients with severe symptoms and older age are related to a less response trajectory. These clinical predictors may help guide treatment selection.

Rapid establishment of murine gastrointestinal organoids using mechanical isolation method.

Gastrointestinal (GI) diseases, including pathological dysplasia, inflammation, neoplasia and injury, suffer millions of patients globally per year. Organoids, three-dimensional cell mass structures supported by biomaterials in dishes, are currently used as a research model for diseases of the small intestine. However, the traditional enzymatic-digestion method for establishing small-intestinal organoids (EnzyOs) is time consuming and often loses the bulk of crypts, a more efficient and reliable method needs to be developed. In this study, using mouse GI organoids as a model, we formulated a rapid mechanical isolation method that could efficiently isolate and culture villi-crypts into small intestinal organoids (MechOs). Primary duodenum organoids generated by MechOs displayed three types of morphology: spheroid, semi-budding and budding, while EnzyOs produced much less budding. Moreover, primary duodenum organoids from MechOs could be subcultured and presented similar gene expression profiles of small intestine specific markers as that from EnzyOs. Importantly, the MechOs method could also be used to generate other types of organoids derived from the stomach, jejunum-ileum, sigmoid-rectum and bile cysts. Taken together, the results show that MechOs could efficiently and economically generate digestive system organoids, providing a potential basis of epithelial organoids for the clinical treatment of gastroenterological diseases.

Comprehensive role of SARS-CoV-2 spike glycoprotein in regulating host signaling pathway.

Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literature, the characteristics and pathogenic mechanisms of the virus, and epidemiological and clinical features of the disease are being rapidly discovered. The spike glycoprotein (S protein), as a key antigen of SARS-CoV-2 for developing vaccines, antibodies, and drug targets, has been shown to play an important role in viral entry, tissue tropism, and pathogenesis. In this review, we summarize the molecular mechanisms of interaction between S protein and host factors, especially receptor-mediated viral modulation of host signaling pathways, and highlight the progression of potential therapeutic targets, prophylactic and therapeutic agents for prevention and treatment of SARS-CoV-2 infection.

Identification of pimavanserin tartrate as a potent Ca2+-calcineurin-NFAT pathway inhibitor for glioblastoma therapy.

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor, and 95% of patients die within 2 years after diagnosis. In this study, aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ), we carried out research to discover a novel alternative drug targeting the oncogenic NFAT signaling pathway for GBM therapy. To accelerate the drug's clinical application, we took advantage of a drug repurposing strategy to identify novel NFAT signaling pathway inhibitors. After screening a set of 93 FDA-approved drugs with simple structures, we identified pimavanserin tartrate (PIM), an effective 5-HT2A receptor inverse agonist used for the treatment of Parkinson's disease-associated psychiatric symptoms, as having the most potent inhibitory activity against the NFAT signaling pathway. Further study revealed that PIM suppressed STIM1 puncta formation to inhibit store-operated calcium entry (SOCE) and subsequent NFAT activity. In cellula, PIM significantly suppressed the proliferation, migration, division, and motility of U87 glioblastoma cells, induced G1/S phase arrest and promoted apoptosis. In vivo, the growth of subcutaneous and orthotopic glioblastoma xenografts was markedly suppressed by PIM. Unbiased omics studies revealed the novel molecular mechanism of PIM's antitumor activity, which included suppression of the ATR/CDK2/E2F axis, MYC, and AuroraA/B signaling. Interestingly, the genes upregulated by PIM were largely associated with cholesterol homeostasis, which may contribute to PIM's side effects and should be given more attention. Our study identified store-operated calcium channels as novel targets of PIM and was the first to systematically highlight the therapeutic potential of pimavanserin tartrate for glioblastoma.

Ameliorative effect of acetylshikonin on cigarette smoke-induced lung inflammation in mice.

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Acetylshikonin was the active principle component of Purple Gromwell that show anti-oxidative and anti-inflammatory effect. However, no data are available to elucidate the protective effect of acetylshikonin on COPD. Acetylshikonin could attenuate smoke-induced lung pathological changes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein 1 (MCP-1) productions, and tissue damages caused by oxidative stress. Furthermore, acetylshikonin was found to enhance the expression of Nrf2 and Nur77-mediated COX-2 in vivo and in vitro.

Uncovering the Mechanism Behind the Improved Stability of 2D Organic-Inorganic Hybrid Perovskites.

2D organic-inorganic hybrid perovskites (OIHPs) may resolve the stability problem of bulk OIHPs. First-principles calculations are employed to investigate the mechanism behind their favorable material properties. Two processes are identified to play a critical role: First, the 2D structure supports additional distortions that enhance the intrinsic structural stability. Second, the surface terminations of 2D OIHPs suppress degradation effects due to humidity. Having uncovered the stabilization mechanism, 2D OIHPs are designed with optimal stability and favorable electronic properties.

Multicenter randomized controlled trial of bifrontal, bitemporal, and right unilateral electroconvulsive therapy in major depressive disorder.

AIM: Electroconvulsive therapy (ECT) has been shown to be the most effective and rapid treatment for severe depression. Electrode placement is one of the most important factors that affect ECT's efficacy and side-effects profile. Bifrontal, bitemporal, and unilateral are the three most used electrode placements. Very few studies have directly compared the efficacy and cognitive side-effects of the three placements. The aim of this study was to compare the efficacy and cognitive side-effects associated with bifrontal, bitemporal, and unilateral electrode placements. METHODS: This multicenter randomized, blinded, controlled trial included 40 patients in each of the three groups. Most of the patients (94.8%) completed six ECT treatments. We used mixed-model analyses to compare differences in 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression (CGI) scores among the three groups and the five times series (baseline, Week 1, Week 2, Week 3, and Week 4). The cognitive outcome was Mini-Mental State Examination (MMSE) score. RESULTS: HAMD-17 and CGI scores did not differ significantly across the groups (HAMD-17 scores: z = -1.13, P = 0.259; CGI scores: z = -0.35, P = 0.729). MMSE scores at pre- and post-ECT were similar across the three groups (F = 2.06, P = 0.133). However, subgroup analysis using paired t-tests showed that MMSE scores improved in the right unilateral and bifrontal groups (t = 2.745, P = 0.0098; t = 2.464, P = 0.0204), but did not change in the bitemporal group (t = 1.188, P = 0.2461). CONCLUSION: The efficacy of right unilateral and bifrontal ECT placement was similar to that of bitemporal ECT. The physical side-effects were also similar across the three groups. Right unilateral and bifrontal ECT placement were associated with improved cognitive outcomes, but bitemporal ECT placement was not.

Modulating the Surface State of SiC to Control Carrier Transport in Graphene/SiC.

Silicon carbide (SiC) with epitaxial graphene (EG/SiC) shows a great potential in the applications of electronic and photoelectric devices. The performance of devices is primarily dependent on the interfacial heterojunction between graphene and SiC. Here, the band structure of the EG/SiC heterojunction is experimentally investigated by Kelvin probe force microscopy. The dependence of the barrier height at the EG/SiC heterojunction to the initial surface state of SiC is revealed. Both the barrier height and band bending tendency of the heterojunction can be modulated by controlling the surface state of SiC, leading to the tuned carrier transport behavior at the EG/SiC interface. The barrier height at the EG/SiC(000-1) interface is almost ten times that of the EG/SiC(0001) interface. As a result, the amount of carrier transport at the EG/SiC(000-1) interface is about ten times that of the EG/SiC(0001) interface. These results offer insights into the carrier transport behavior at the EG/SiC heterojunction by controlling the initial surface state of SiC, and this strategy can be extended in all devices with graphene as the top layer.

Divergence of a Tandem Duplication of Manganese Superoxide Dismutase in Nosema bombycis.

Manganese superoxide dismutase (MnSOD) is a key enzyme in the protection of cells from oxidative stress. A tandem duplication of the MnSOD gene (NbMnSOD1 and NbMnSOD2) in the genome of Nosema bombycis, a parasite of the silkworm Bombyx mori, was previously identified. Here, we compare the protein structures of NbMnSOD1 and NbMnSOD2 and characterize these two proteins in terms of cellular localization, timing of transcription, protein structure, and enzyme activity. Despite a similarity in the primary sequence of NbMnSOD1 and NbMnSOD2, the latter shows a remarkable degree of amino acid sequence difference on the protein's surface and in the active site, where there is a substitution of a phenylalanine for a histidine in NbMnSOD2. Immuno-electron microscopy demonstrates that NbMnSOD1 is present in the cytosol of mature spores, whereas NbMnSOD2 is localized on the polar tube and the spore wall. Immunofluorescence confirms the localization of NbMnSOD2 on the polar tube of the germinated spore. Quantitative measurement of gene expression (qRT-PCR) demonstrates production of both alleles during the first day of infection followed by a dramatic decrease during the second to fourth day of infection. From the fifth day onward, the two alleles show a complementary pattern of expression. The qRT-PCR of the host manganese superoxide dismutase (BmMnSOD) shows a notable increase in transcription upon infection, leading to a three-fold spike by the first day of infection, followed by a decrease in transcription. Measurement of overall MnSOD activity shows a similar peak at day 1 followed by a decrease to a constant rate of enzyme activity. The differences in cellular localization and pattern of gene expression of NbMnSOD2 compared to NbMnSOD1, as well as the differences in protein structure seen for NbMnSOD2 compared to other microsporidial MnSODs, strongly suggest a unique, recently evolved role for NbMnSOD2.

The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases.

Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green leafy vegetables, orange and yellow fruits that form the macular pigment of the human eyes. It was hypothesized that they protect against visual disorders and cognition diseases, such as age-related macular degeneration (AMD), age-related cataract (ARC), cognition diseases, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, uveitis and diabetic retinopathy. The mechanism by which they are involved in the prevention of eye diseases may be due their physical blue light filtration properties and local antioxidant activity. In addition to their protective roles against light-induced oxidative damage, there are increasing evidences that L and Z may also improve normal ocular function by enhancing contrast sensitivity and by reducing glare disability. Surveys about L and Z supplementation have indicated that moderate intakes of L and Z are associated with decreased AMD risk and less visual impairment. Furthermore, this review discusses the appropriate consumption quantities, the consumption safety of L, side effects and future research directions.

The well-accepted notion that gene amplification contributes to increased expression still remains, after all these years, a reasonable but unproven assumption.

"Gene amplification causes overexpression" is a longstanding and well-accepted concept in cancer genetics. However, raking the whole literature, we find only statistical analyses showing a positive correlation between gene copy number and expression level, but do not find convincing experimental corroboration for this notion, for most of the amplified oncogenes in cancers. Since an association does not need to be an actual causal relation, in our opinion, this widespread notion still remains a reasonable but unproven assumption awaiting experimental verification.

[Comparative Analysis of Content of Four Alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea].

OBJECTIVE: To establish an assay method for simultaneous determination of peimine, peiminine, peimissine and hupehenine and to make a comparative analysis of the content of four alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea for the first time. METHODS: A Unitary C18 column(250 mm x 4.6 mm, 5 µm) was chosen with acetonitrile-water (containing 0.05% diethylamine) as mobile phase in a gradient program. The column temperature was 35 degrees C and the flow-rate was 1.0 mL/min. RESULTS: There was high content of peiminine and the content of peimissine was inferior to peiminine in Fritillaria hupehensis. Relatively speaking, peimine and hupehenine were much lower than the other two ingredients. Fritillaria ebeiensis var. purpurea also contained high levels of peiminine, the minimum content of peimine and equivalent content of peimissine comparing with Fritillaria hupehensis. In addition, it didn't contain hupehenine in Fritillaria ebeiensis var. purpurea. CONCLUSION: This method is simple and fast, and it has good separation, reproducibility and reliable results. Also, it can be used as basis for the quality evaluation of Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea.

Sequence analysis of EBV immediate-early gene BZLF1 and BRLF1 in lymphomas.

The immediate-early (IE) genes, BZLF1 and BRLF1, play an important role in switching Epstein-Barr virus from the latent to the lytic state. The functions of the two IE genes and their respective proteins: ZEBRA and Rta have been well studied, but little is known about their DNA coding sequence variations and disease association. In order to investigate the sequence variation patterns and elucidate their association with lymphomas, BZLF1 and BRLF1 were analyzed in 26 and 33 lymphomas using PCR-direct sequencing method respectively. Three sequence variation types of BZLF1 gene were identified. The type BZLF1-A and BZLF1-B was detected in 34.6% (9/26) and 57.7% (15/26) of the tumor specimens, respectively. Among the three functional domains of ZEBRA, the transactivation domain had the most mutations. Three variation types were also identified in BRLF1 gene where type BR1-A and BR1-C were detected in 27.3% (9/33) and 69.7% (23/33) of specimens, respectively. Among the three functional domains of Rta, the dimerization domain was well conserved while multiple mutations were detected in both the DNA binding domain and the transactivation domain. The variation types BZLF1-B and BR1-C were more frequent in the lymphomas, compared with the throat washing samples from the healthy donors. These results suggest that the type BZLF1-B and BR1-C may be associated with the tumorigenesis of lymphoma.

Nonvolatile and reconfigurable two-terminal electro-optic duplex memristor based on III-nitride semiconductors.

With the fast development of artificial intelligence (AI), Internet of things (IOT), etc, there is an urgent need for the technology that can efficiently recognize, store and process a staggering amount of information. The AlScN material has unique advantages including immense remnant polarization, superior temperature stability and good lattice-match to other III-nitrides, making it easy to integrate with the existing advanced III-nitrides material and device technologies. However, due to the large band-gap, strong coercive field, and low photo-generated carrier generation and separation efficiency, it is difficult for AlScN itself to accumulate enough photo-generated carriers at the surface/interface to induce polarization inversion, limiting its application in in-memory sensing and computing. In this work, an electro-optic duplex memristor on a GaN/AlScN hetero-structure based Schottky diode has been realized. This two-terminal memristor shows good electrical and opto-electrical nonvolatility and reconfigurability. For both electrical and opto-electrical modes, the current on/off ratio can reach the magnitude of 104, and the resistance states can be effectively reset, written and long-termly stored. Based on this device, the "IMP" truth table and the logic "False" can be successfully reproduced, indicating the huge potential of the device in the field of in-memory sensing and computing.

Effect and Regulation Mechanism of Post-deposition Annealing on the Ferroelectric Properties of AlScN Thin Films.

Integrating ferroelectric AlScN with III-N semiconductors to enhance the performance and tunability of nitride devices requires high-quality AlScN films. This work focuses on the effect and regulation mechanism of post-annealing in pure N2 on the crystal quality and ferroelectric properties of AlScN films. It is found that the crystal quality improves with increasing annealing temperatures. Remarkably, the leakage current of AlScN films caused by grain boundaries could be reduced by four orders of magnitude after annealing at 400 °C. The crystal growth dynamics simulations and band structure calculations indicate that the energy supplied by the temperature facilitates the evolution of abnormally oriented grains to have a better c-axis orientation, resulting in the defect states at the Fermi-level disappearing, which is mainly the reason for the leakage current decrease. More interestingly, the reduction of leakage current leads to the previously leaking region exhibiting ferroelectric properties, which is of great significance to improve the ferroelectricity of AlScN and ensure the uniformity of devices. Furthermore, annealing enhances the tensile strain on the film, which flattens the energy landscape of ferroelectric switching and reduces the coercive field. However, the risk of incorporation of oxygen will also be increased if the annealing temperatures are higher than 400 °C, which will not only reduce the relative displacement of metal atoms and nitrogen atoms in AlScN but also enhance the ferroelectric depolarization field, leading to the remnant polarization decreasing dramatically. These discoveries facilitate a deeper understanding of the influencing mechanism on the ferroelectric properties of AlScN films and provide a direction for obtaining high-quality AlScN.

Wafer-Scale Growth and Transfer of High-Quality MoS2 Array by Interface Design for High-Stability Flexible Photosensitive Device.

Transition metal disulfide compounds (TMDCs) emerges as the promising candidate for new-generation flexible (opto-)electronic device fabrication. However, the harsh growth condition of TMDCs results in the necessity of using hard dielectric substrates, and thus the additional transfer process is essential but still challenging. Here, an efficient strategy for preparation and easy separation-transfer of high-uniform and quality-enhanced MoS2 via the precursor pre-annealing on the designed graphene inserting layer is demonstrated. Based on the novel strategy, it achieves the intact separation and transfer of a 2-inch MoS2 array onto the flexible resin. It reveals that the graphene inserting layer not only enhances MoS2 quality but also decreases interfacial adhesion for easy separation-transfer, which achieves a high yield of ≈99.83%. The theoretical calculations show that the chemical bonding formation at the growth interface has been eliminated by graphene. The separable graphene serves as a photocarrier transportation channel, making a largely enhanced responsivity up to 6.86 mA W-1, and the photodetector array also qualifies for imaging featured with high contrast. The flexible device exhibits high bending stability, which preserves almost 100% of initial performance after 5000 cycles. The proposed novel TMDCs growth and separation-transfer strategy lightens their significance for advances in curved and wearable (opto-)electronic applications.