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.

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.

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.

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.

The AlN lattice-polarity inversion in a high-temperature-annealed c-oriented AlN/sapphire originated from the diffusion of Al and O atoms from sapphire.

AlN films are widely used owing to their superior characteristics, including an ultra-wide bandgap, high breakdown field, and radiation resistance. High-temperature annealing (HTA) makes it easy to obtain high-quality AlN films, with the advantages of a simple process, good repeatability, and low cost. However, it is always found that there is a lattice-polarity inversion from a N-polarity near the sapphire to an Al-polarity in the HTA c-oriented AlN/sapphire. Currently, the formation mechanism is still unclear, which hinders its further wide applications. Therefore, the formation mechanism of the polarity inversion and its impacts on the quality and stress profile of the upper AlN in the HTA c-oriented AlN/sapphire were investigated. The results imply that the inversion originated from the diffusion of the Al and O atoms from the sapphire. Due to the presence of abundant Al vacancies (VAl) in the upper AlN, Al atoms in the sapphire diffuse into the upper AlN during the annealing to fill the VAl, resulting in the O-terminated sapphire, leading to the N-polar AlN. Meanwhile, O atoms in the sapphire also diffuse into the upper AlN during the annealing, forming an AlxOyNz layer and causing the inversion from N- to Al-polarity. The inversion has insignificant impacts on the quality and stress distribution of the upper AlN. Besides, this study predicts the presence of a two-dimensional electron gas at the inversion interface. However, the measured electron concentration is much lower than that predicted, which may be due to the defect compensation, low polarization level, and strong impurity scattering.

Centimeter-Transferable III-Nitride Membrane Enabled by Interfacial Adhesion Control for a Flexible Photosensitive Device.

Flexible III-nitride-based optoelectronic devices are crucial for the next-generation foldable/wearable lighting sterilization and sensor working in the ultraviolet (UV) region. However, the strong bonding effect at the epitaxial interface of III-nitride and bare sapphire substrate makes it difficult for epilayer separation and flexible applications. Although the emerging van der Waals epitaxy (vdWE) with graphene insertion layer offers a feasible route for weakening the interfacial adhesion, the intact centimeter-transferable III-nitride membrane still remains challenging. The spontaneous delamination occurs due to the too weak interfacial adhesion of pure vdW force, and on the contrary, the structural damage of graphene by high-temperature hydrogen etching during the III-nitride growth might also cause separation failure. Up to now, the efficient control of vdWE interfacial adhesion is still an on-going research hotspot. Herein, we demonstrate the interfacial adhesion control of III-nitride vdWE by utilizing graded high-temperature nitridation treatment of the graphene insertion layer, which generates defects and N doping in different levels. The corresponding epitaxial modes of pure-vdWE, quasi-vdWE, and mixed epitaxy are achieved according to the interfacial adhesion difference. It reveals that the quasi-vdWE enabled by small graphene defects and proper N doping triggers the low formation energy for AlN nucleation; meanwhile, the proper interfacial adhesion ensures the growth integrality and intact separation of III-nitride membrane in the centimeter scale. The UV resin-assisted bonding technique is proposed for the successful transfer of III-nitride onto a flexible substrate. The flexible photodetector is fabricated by using a graphene monolayer as the photocarrier transport channel, and it achieves a high device yield of 90%, retaining ∼60% of its initial performance after 250 bending cycles. This work offers the promising strategy for controlling vdWE interfacial adhesion, and the separable and transferable III-nitride membrane lays the foundation for advances of future UV foldable and wearable devices.

Discovery of [5,5'-bibenzo[d][1,3]dioxol]-6-substituted amine derivatives as potent proprotein convertase subtilisin/kexin type 9 inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hyperlipidemia. In discovery of novel small molecules that interfere PCSK9/LDLR protein-protein interaction (PPI), structural modification was performed based on our previously derived compounds. A series of [5,5'-bibenzo[d][1,3]dioxol]-6-amine analogs were designed and synthesized for the activity evaluation. In the PCSK9/LDLR PPI impairing test, molecules D28 and D29, exhibited remarkable inhibitory potency with IC50 values of 8.30 and 6.70 µM compared with SBC-115337 (17.89 µM), respectively. Molecular docking predicted the binding pattern of compounds D28 and D29 in the LDLR binding site of PCSK9. Hydrophobic interactions play an important role in the binding of aromatic molecular fragments to the pockets in the PCSK9/LDLR binding interface. Further LDLR expression and LDL uptake studies revealed that both D28 and D29 restored LDLR expression on the surface of hepatic HepG2 cells and improved extracellular LDL uptake in the presence of PCSK9. It is significant that molecules D28 and D29 exhibited potential for the treatment of hyperlipidemia in current in vitro investigations. Generally, lead compounds with novel structures were developed in the present study for further design of lipid-lowering molecules by targeting PCSK9/LDLR PPI.

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.

Predicting tumor deposits in patients with rectal cancer: Using the models of multiple mathematical parameters derived from diffusion-weighted imaging.

PURPOSE: Using mono-exponential, bi-exponential, and stretched-exponential models of multi-b-value diffusion-weighted imaging (DWI) to predict tumor depositions (TDs) in patients with rectal cancer (RC). MATERIAL AND METHODS: This retrospective study, between January 2018 and November 2021, enrolled 30 TDs-positive and 38 TDs-negative of patients with rectal cancer. The mathematical parameters including ADC from mono-exponential model, D, D* and f from bi-exponential model, and DDC and α from stretched-exponential model, clinical factors (such as age, gender, pathological stage, etc.) and image features (such as length, thickness, location, etc.) from tumor characteristics were obtained to identify the two groups of patients. The results were evaluated by the receiver operating characteristic curve (ROC) analysis and area under the ROC curve (AUC). Multivariate binary logistic regression analysis was conducted to determine the independent risk factors. RESULTS: The D* and α values, pt. stage, tumor location, mesorecta fascia (MRF) / peritoneum status and percentage of rectal wall circumference invaded (PCI) were significantly different between the TDs-positive and TDs-negative groups (P < 0.001, P < 0.001, P = 0.029, P = 0.008, P < 0.001 and P = 0.002, respectively), with the AUC were 0.838, 0.901, 0.618, 0.698 0.694 and 0.758, respectively. The D* and α values were proved to be independent risk factors after multivariate binary logistic regression analysis (p = 0.022 and 0.004, respectively). The AUC of the model consisting of the D* and α values was 0.913 (95 % CI 0.820 âˆ¼ 0.968).The combined model constructed by D*, α and tumor location demonstrated superior diagnostic performance, with the AUC, sensitivity, specificity, and accuracy of 0.947 (95 % confidence interval, CI, 0.865-0.987), 0.900, 0.868 and 0.853, respectively. CONCLUSION: Multiple mathematical parameters can be used as preoperative auxiliary diagnostic tools to predict TDs of RC. The combined model constructed by D*, α and tumor location show better diagnostic performance for TDs.

Development and validation of a high-resolution T2WI-based radiomic signature for the diagnosis of lymph node status within the mesorectum in rectal cancer.

Purpose: The aim of this study was to explore the feasibility of a high-resolution T2-weighted imaging (HR-T2WI)-based radiomics prediction model for diagnosing metastatic lymph nodes (LNs) within the mesorectum in rectal cancer. Method: A total of 604 LNs (306 metastatic and 298 non-metastatic) from 166 patients were obtained. All patients underwent HR-T2WI examination and total mesorectal excision (TME) surgery. Four kinds of segmentation methods were used to select region of interest (ROI), including method 1 along the border of LNs; method 2 along the expanded border of LNs with an additional 2-3 mm; method 3 covering the border of LNs only; and method 4, a circle region only within LNs. A total of 1,409 features were extracted for each method. Variance threshold method, Select K Best, and Lasso algorithm were used to reduce the dimension. All LNs were divided into training and test sets. Fivefold cross-validation was used to build the logistic model, which was evaluated by the receiver operating characteristic (ROC) with four indicators, including area under the curve (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). Three radiologists with different working experience in diagnosing rectal diseases assessed LN metastasis respectively. The diagnostic efficiencies with each of four segmentation methods and three radiologists were compared to each other. Results: For the test set, the AUCs of four segmentation methods were 0.820, 0.799, 0.764, and 0.741; the ACCs were 0.725, 0.704, 0.709, and 0.670; the SEs were 0.756, 0.634, 0.700, and 0.589; and the SPs were 0.696, 0.772, 0.717, and 0.750, respectively. There was no statistically significant difference in AUC between the four methods (p > 0.05). Method 1 had the highest values of AUC, ACC, and SE. For three radiologists, the overall diagnostic efficiency was moderate. The corresponding AUCs were 0.604, 0.634, and 0.671; the ACCs were 0.601, 0.632, and 0.667; the SEs were 0.366, 0.552, and 0.392; and the SPs were 0.842, 0.715, and 0.950, respectively. Conclusions: The proposed HR-T2WI-based radiomic signature exhibited a robust performance on predicting mesorectal LN status and could potentially be used for clinicians in order to determine the status of metastatic LNs in rectal cancer patients.

Intravoxel incoherent motion DWI with different mathematical models in predicting rectal adenoma with and without canceration.

PURPOSE: To evaluate the clinical value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) with mono-exponential (ME), bi-exponential (BE), and stretched-exponential (SE) models for predicting rectal adenomas with canceration. MATERIAL AND METHODS: Sixty patients with postoperative pathology-confirmed rectal adenoma (n = 31) and adenoma with canceration (n = 29) were enrolled and underwent IVIM-DWI scanning. The ME-derived apparent diffusion coefficient (ADC), BE-derived true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), SE-derived distributed diffusion coefficient (DDC), and water molecular diffusion heterogeneity index (α) were measured. The differences in each parameter between adenoma and canceration were compared. Multivariate binary logistic regression analysis was used to establish models for predicting rectal adenomas with canceration. Receiver operating characteristic curve analysis was applied to evaluate diagnostic performances of each model in terms of sensitivity, specificity, accuracy, and area under the curve (AUC). RESULTS: The AUCs of ADC, D, D*, f, DDC and α were 0.851 (95 % confidence interval, CI, 0.735-0.930), 0.895 (95 % CI, 0.789-0.960), 0.720 (95 % CI, 0.589-0.828), 0.791 (95 % CI, 0.667-0.886), 0.841 (95 % CI, 0.724-0.923) and 0.738 (95 % CI, 0.608-0.834), respectively. The AUCs of BE and SE models were 0.927 (95 % CI, 0.829-0.978) and 0.874 (95 % CI, 0.763-0.946), respectively. The AUC, sensitivity, specificity, and accuracy of the derived four values (ADC, D, f, and DDC) from the combination of three models were 0.950, 96.6 % (95 % CI, 95.3-97.6 %), 80.6 % (95 % CI, 78.0-82.9 %), and 88.3 % (95 % CI, 86.2-90.2 %), respectively. CONCLUSION: ADC can easily and effectively predict rectal adenomas with canceration. The BE model has a better combination of sensitivity and specificity for the diagnosis of rectal adenoma canceration.

Van der Waals Epitaxy of c-Oriented Wurtzite AlGaN on Polycrystalline Mo Substrates for Enhanced Heat Dissipation.

The epitaxy of III-nitrides on metallic substrates is competitive due to the advantages of vertical carrier injection, enhanced heat dissipation, and flexible application in various III-nitride-based devices. However, the serious lattice mismatch, atom diffusion, and interface reaction under the rigorous growth conditions have caused enormous obstacles. Based on the thermal and chemical stability of the graphene layer, we propose the van der Waals epitaxy of c-oriented wurtzite AlGaN on the polycrystalline Mo substrate by high-temperature metal-organic chemical vapor deposition. The insertion of a graphene layer interrupts the chaotic epitaxial relationship between the polycrystalline metal and epilayers, resulting in the single-crystalline orientation along the wurtzite (0002) plane and residual stress release in AlGaN because of the weak van der Waals interaction. We also demonstrate that the epitaxy of AlGaN on Mo metal possesses enhanced heat dissipation ability, in which the epilayer temperature is controlled at only 28.7 °C by the heating of a ∼54 °C hot plate. The heat dissipation enhancement for the present epitaxial structures provides a desirable strategy for the fabrication of efficient ultraviolet devices with excellent stability and lifetime.

Morphology and carrier mobility of high-B-content BxAl1-xN ternary alloys from an ab initio global search.

The excellent properties of III-nitrides and their alloys have led to significant applications in optoelectronic devices. Boron, the lightest IIIA group element, makes it possible to extend the flexibility of III-nitride alloys. However, both BxAl1-xN and BxGa1-xN ternary alloys suffer from poor material quality during crystal growth, their B contents in experimental reports are no higher than 22%, and the underlying mechanism is still unclear. Herein, ab initio global calculation by particle swarm optimization combined with density functional theory is carried out to identify the ground structures of BxAl1-xN alloys with different B contents (x = 0.25, 0.5, and 0.75). Furthermore, the electronic properties and intrinsic carrier mobility are studied. For B0.25Al0.75N and B0.75Al0.25N, quasi-wurtzite and quasi-hexagonal structures are energetically favourable, respectively, indicating a wurtzite-to-hexagonal structural transition due to the three-coordinated B atoms being incorporated into the lattice. When the B content is 50%, B0.5Al0.5N shows a ten-membered ring structure with an indirect bandgap of 3.52 eV and strong anisotropy of mobility. Our results uncover the mechanism of the structural and electronic property evolution with B content and pave a route for the application of B-containing III-nitride alloys.

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.

Comparison of electroconvulsive therapy and magnetic seizure therapy in schizophrenia: Structural changes/neuroplasticity.

Electroconvulsive therapy (ECT) can effectively reduce the symptoms of schizophrenia, but may also impair cognitive function. A potential alternative is magnetic seizure therapy (MST), which has shown comparable efficacy with less severe cognitive disruption. This study compared ECT to MST for clinical efficacy and cognitive side effects. In addition, we examined the possible contributions of hippocampal volume changes and enhanced brain derived neurotrophic factor (BDNF) signaling to the therapeutic responses. Thirty-four confirmed schizophrenia patients were allocated to receive ECT (n = 16) or MST (n = 18) over a 4-week period. Schizophrenia symptoms were measured by PANSS, cognition by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum BDNF and its precursor proBDNF by ELISA at baseline and following ECT or MST. Both treatments reduced PANSS scores with comparable efficacy, while MST was superior for preservation of RBANS language score. ECT significantly increased the volumes of the bilateral hippocampus and multiple subfields, while MST had no effect on hippocampal volume. The change in right hippocampal volume was correlated with proBDNF change among ECT and MST non-responders (< 25% decrease in PANSS score). MST reduced schizophrenia symptoms as effectively as ECT with slightly better preservation of cognitive function.

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.

Diagnostic and Staging Value of Serum Angiotensin-Converting Enzyme in Sarcoidosis.

OBJECTIVE: To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis. METHODS: Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. RESULTS: A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L, P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients (P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients (P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = -0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819. CONCLUSION: sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis.

Functional reconfiguration of cerebellum-cerebral neural loop in schizophrenia following electroconvulsive therapy.

Recent evidence highlights the role of the cerebellum-cerebral loop in the pathophysiology of schizophrenia (SZ). Electroconvulsive therapy (ECT) is clinically applied to augment the effect of antipsychotic drugs. The study aims to address whether the cerebellum-cerebral loop is involved in the mechanisms of ECT's augmentation effect. Forty-two SZ patients and 23 healthy controls (HC) were recruited and scanned using resting-state functional MRI (rs-fMRI). Twenty-one patients received modified ECT plus antipsychotics (MSZ group), and 21 patients took antipsychotics only (DSZ group). All patients were re-scanned four weeks later. Brain functional network was constructed according to the graph theory. The sub-network exhibited longitudinal changes after ECT or medications were constructed. For the MSZ group, a sub-network involving default-mode network and cerebellum showed significant longitudinal changes. For the DSZ group, a different sub-network involving the thalamus, frontal and occipital cortex was found to be altered in the follow-up scan. In addition, the changing FC of the left cerebellar crus2 region was correlated with the changing scores of the psychotic symptoms only in the MSZ group but not in the DSZ group. In conclusion, the cerebral-cerebellum loop is possibly involved in the antipsychotic mechanisms of ECT for schizophrenia.

Magnetic Seizure Therapy Compared to Electroconvulsive Therapy for Schizophrenia: A Randomized Controlled Trial.

Background: Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). However, reports on the use of MST for patients with schizophrenia, particularly in developing countries, which is a main indication for ECT, are limited. Methods: From February 2017 to July 2018, 79 inpatients who met the DSM-5 criteria for schizophrenia were randomized to receive 10 sessions of MST (43 inpatients) or ECT (36 inpatients) over the course of 4 weeks. At baseline and 4-week follow-up, the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess symptom severity and cognitive functions, respectively. Results: Seventy-one patients who completed at least half of the treatment protocol were included in the per-protocol analysis. MST generated a non-significant larger antipsychotic effect in terms of a reduction in PANSS total score [g = 0.17, 95% confidence interval (CI) = -0.30, 0.63] and response rate [relative risk (RR) = 1.41, 95% CI = 0.83-2.39]. Twenty-four participants failed to complete the cognitive assessment as a result of severe psychotic symptoms. MST showed significant less cognitive impairment over ECT in terms of immediate memory (g = 1.26, 95% CI = 0.63-1.89), language function (g =1.14, 95% CI = 0.52-1.76), delayed memory (g = 0.75, 95% CI = 0.16-1.35), and global cognitive function (g = 1.07, 95% CI = 0.45-1.68). The intention-to-treat analysis generated similar results except for the differences in delayed memory became statistically insignificant. Better baseline cognitive performance predicted MST and ECT response. Conclusions: Compared to bitemporal ECT with brief pulses and age-dose method, MST had similar antipsychotic efficacy with fewer cognitive impairments, indicating that MST is a promising alternative to ECT as an add-on treatment for schizophrenia. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02746965.

Proteomic Profiling Identifies Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Encoded LANASIM-Associated Proteins in Hypoxia.

Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.