Thin-film transistor for temporal self-adaptive reservoir computing with closed-loop architecture.

Reservoir computing is a powerful neural network-based computing paradigm for spatiotemporal signal processing. Recently, physical reservoirs have been explored based on various electronic devices with outstanding efficiency. However, the inflexible temporal dynamics of these reservoirs have posed fundamental restrictions in processing spatiotemporal signals with various timescales. Here, we fabricated thin-film transistors with controllable temporal dynamics, which can be easily tuned with electrical operation signals and showed excellent cycle-to-cycle uniformity. Based on this, we constructed a temporal adaptive reservoir capable of extracting temporal information of multiple timescales, thereby achieving improved accuracy in the human-activity-recognition task. Moreover, by leveraging the former computing output to modify the hyperparameters, we constructed a closed-loop architecture that equips the reservoir computing system with temporal self-adaptability according to the current input. The adaptability is demonstrated by accurate real-time recognition of objects moving at diverse speed levels. This work provides an approach for reservoir computing systems to achieve real-time processing of spatiotemporal signals with compound temporal characteristics.

Identification of key modules and driving genes in nonalcoholic fatty liver disease by weighted gene co-expression network analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition, and progresses to liver cirrhosis, and even hepatocellular carcinoma. However, the invasive diagnosis of NAFLD with histopathological evaluation remains risky. This study investigated potential genes correlated with NAFLD, which may serve as diagnostic biomarkers and even potential treatment targets. METHODS: The weighted gene co-expression network analysis (WGCNA) was constructed based on dataset E-MEXP-3291. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the function of genes. RESULTS: Blue module was positively correlated, and turquoise module negatively correlated with the severity of NAFLD. Furthermore, 8 driving genes (ANXA9, FBXO2, ORAI3, NAGS, C/EBPα, CRYAA, GOLM1, TRIM14) were identified from the overlap of genes in blue module and GSE89632. And another 8 driving genes were identified from the overlap of turquoise module and GSE89632. Among these driving genes, C/EBPα (CCAAT/enhancer binding protein α) was the most notable. By validating the expression of C/EBPα in the liver of NAFLD mice using immunohistochemistry, we discovered a significant upregulation of C/EBPα protein in NAFLD. CONCLUSION: we identified two modules and 16 driving genes associated with the progression of NAFLD, and confirmed the protein expression of C/EBPα, which had been paid little attention to in the context of NAFLD, in the present study. Our study will advance the understanding of NAFLD. Moreover, these driving genes may serve as biomarkers and therapeutic targets of NAFLD.

Integration of Protein Nanocage with CpG Motifs: A Virus-Mimicked Core-Shell Nanostructure to Ignite Antitumor Immunity.

The tumor microenvironment typically possesses immunosuppressive properties that hinder the effectiveness of antitumor immune responses, even in the context of immunotherapies. However, it is observed that pathogenic microorganisms can trigger strong immune responses during infection, offering a potential means to counteract the immunosuppressive environment of tumors. In this study, a protein nanocage called CpG@HBc nanocages (NCs) is developed, which mimics the structure of the hepatitis B virus and combines with an immunostimulatory component known as cytosine phosphoguanosine oligonucleotide (CpG). By delivering these immunostimulatory agents, CpG@HBc NCs are able to effectively reverse the suppressive tumor microenvironment, resulting in the inhibition of poorly immunogenic tumors in mice. Through high-dimensional mass cytometry (CyTOF) analysis, remarkable alterations in immune responses is observed induced by CpG@HBc. Treatment with immunogenic CpG@HBc NCs, along with co-injection of an OX40 agonist, sensitized colorectal cancer tumors to T cell immune responses, resulting in significant impairment of tumor growth and robust immune activation. Furthermore, CpG@HBc NCs induced long-term antitumor immunological memory, protecting tumor-cured mice from tumor rechallenge. Overall, these findings highlight the potential of a virus-inspired protein nanocage to mimic anti-viral immunity and offer a unique therapeutic approach for cancer immunotherapy.

Themis suppresses the effector function of CD8+ T cells in acute viral infection.

CD8+ T cells play a central role in antiviral immune responses. Upon infection, naive CD8+ T cells differentiate into effector cells to eliminate virus-infected cells, and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved. Although extensively investigated, the underlying mechanisms of CD8+ T-cell differentiation remain incompletely understood. Themis is a T-cell-specific protein that plays critical roles in T-cell development. Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8+ T-cell homeostasis, cytokine responsiveness, and antibacterial responses. In this study, we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection. We found that preexisting CD8+ T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice. Further analyses showed that in the primary immune response, Themis deficiency promoted the differentiation of CD8+ effector cells and increased their TNF and IFNγ production. Moreover, Themis deficiency impaired memory precursor cell (MPEC) differentiation but promoted short-lived effector cell (SLEC) differentiation. Themis deficiency also enhanced effector cytokine production in memory CD8+ T cells while impairing central memory CD8+ T-cell formation. Mechanistically, we found that Themis mediates PD-1 expression and its signaling in effector CD8+ T cells, which explains the elevated cytokine production in these cells when Themis is disrupted.

Effects of Source/Drain Electrodes on the Performance of InSnO Thin-Film Transistors.

Oxide thin-film transistors (TFTs) are of increasing interest in the field of advanced displays. In this work, we explore Al, InSnO (ITO), Ti, and Mo as source/drain electrodes of ITO TFTs. A comparison study is conducted on the electrical properties of ITO TFTs with the four categories of source/drain electrodes. Interestingly, the ITO TFT with an Al source/drain electrode exhibits better device performance, such as a field-effect mobility (µFE) of 26.45 cm2/Vs, a reasonable turn-on voltage (VON) of 2.7 V, and a steep subthreshold swing (SS) of 201.50 mV/decade. The contact properties of ITO TFTs are further analyzed, and the results show that the device with an Al electrode exhibits lower contact resistance than the other devices. However, the devices with the four electrode materials all reveal excellent stability under negative bias illumination stress (NBIS) with |ΔVTH| < 1 V. This work paves the way for the practical applications of ITO TFTs in next-generation displays.

Mechanisms of Scaling Effect for Emerging Nanoscale Interconnect Materials.

The resistivity of Cu interconnects increases rapidly with continuously scaling down due to scatterings, causing a major challenge for future nodes in M0 and M1 layers. Here, A Boltzmann-transport-equation-based Monte Carlo simulator, including all the major scattering mechanisms of interconnects, is developed for the evaluation of electron transport behaviors. Good agreements between our simulation and the experimental results are achieved for Cu, Ru, Co, and W, from bulk down to 10 nm interconnects. The line resistance values of the four materials with the inclusion of liner and barrier thicknesses are calculated in the same footprint for a fair comparison. The impact of high aspect ratio on resistivity is analyzed for promising buried power rail materials, such as Ru and W. Our results show that grain boundary scattering plays the most important role in nano-scale interconnects, followed by surface roughness and plasma excimer scattering. Surface roughness scattering is the origin of the resistivity decrease for high-aspect-ratio conductive rails. In addition, the grain sizes for the technical nodes of different materials are extracted and the impact of grain size on resistivity is analyzed.

Structural Engineering Effects on Hump Characteristics of ZnO/InSnO Heterojunction Thin-Film Transistors.

Transparent conductive oxides (TCO) have been extensively investigated as channel materials for thin-film transistors (TFTs). In this study, highly transparent and conductive InSnO (ITO) and ZnO films were deposited, and their material properties were studied in detail. Meanwhile, we fabricated ZnO/ITO heterojunction TFTs, and explored the effects of channel structures on the hump characteristics of ZnO/ITO TFTs. We found that Vhump-VON was negatively correlated with the thickness of the bottom ZnO layer (10, 20, 30, and 40 nm), while it was positively correlated with the thickness of the top ITO layer (3, 5, 7, and 9 nm), where Vhump is the gate voltage corresponding to the occurrence of the hump and VON is the turn-on voltage. The results demonstrated that carrier transport forms dual current paths through both the ZnO and ITO layers, synthetically determining the hump characteristics of the ZnO/ITO TFTs. Notably, the hump was effectively eliminated by reducing the ITO thickness to no more than 5 nm. Furthermore, the hump characteristics of the ZnO/ITO TFTs under positive gate-bias stress (PBS) were examined. This work broadens the practical application of TCO and provides a promising method for solving the hump phenomenon of oxide TFTs.

Themis is indispensable for IL-2 and IL-15 signaling in T cells.

To perform their antiviral and antitumor functions, T cells must integrate signals both from the T cell receptor (TCR), which instruct the cell to remain quiescent or become activated, and from cytokines that guide cellular proliferation and differentiation. In mature CD8+ T cells, Themis has been implicated in integrating TCR and cytokine signals. We investigated whether Themis plays a direct role in cytokine signaling in mature T cells. Themis was required for IL-2- and IL-15-driven CD8+ T cell proliferation both in mice and in vitro. Mechanistically, we found that Themis promoted the activation of the transcription factor Stat and mechanistic target of rapamycin signaling downstream of cytokine receptors. Metabolomics and stable isotope tracing analyses revealed that Themis deficiency reduced glycolysis and serine and nucleotide biosynthesis, demonstrating a receptor-proximal requirement for Themis in triggering the metabolic changes that enable T cell proliferation. The cellular, metabolic, and biochemical defects caused by Themis deficiency were corrected in mice lacking both Themis and the phosphatase Shp1, suggesting that Themis mediates IL-2 and IL-15 receptor-proximal signaling by restraining the activity of Shp1. Together, these results not only shed light on the mechanisms of cytokine signaling but also provide new clues on manipulating T cells for clinical applications.

Investigation on Transparent, Conductive ZnO:Al Films Deposited by Atomic Layer Deposition Process.

Transparent electrodes are a core component for transparent electron devices, photoelectric devices, and advanced displays. In this work, we fabricate fully-transparent, highly-conductive Al-doped ZnO (AZO) films using an atomic layer deposition (ALD) system method of repeatedly stacking ZnO and Al2O3 layers. The influences of Al cycle ratio (0, 2, 3, and 4%) on optical property, conductivity, crystallinity, surface morphology, and material components of the AZO films are examined, and current conduction mechanisms of the AZO films are analyzed. We found that Al doping increases electron concentration and optical bandgap width, allowing the AZO films to excellently combine low resistivity with high transmittance. Besides, Al doping induces preferred-growth-orientation transition from (002) to (100), which improves surface property and enhances current conduction across the AZO films. Interestingly, the AZO films with an Al cycle ratio of 3% show preferable film properties. Transparent ZnO thin film transistors (TFTs) with AZO electrodes are fabricated, and the ZnO TFTs exhibit superior transparency and high performance. This work accelerates the practical application of the ALD process in fabricating transparent electrodes.

Effects of Channel Thickness on Electrical Performance and Stability of High-Performance InSnO Thin-Film Transistors.

InSnO (ITO) thin-film transistors (TFTs) attract much attention in fields of displays and low-cost integrated circuits (IC). In the present work, we demonstrate the high-performance, robust ITO TFTs that fabricated at process temperature no higher than 100 °C. The influences of channel thickness (tITO, respectively, 6, 9, 12, and 15 nm) on device performance and positive bias stress (PBS) stability of the ITO TFTs are examined. We found that content of oxygen defects positively correlates with tITO, leading to increases of both trap states as well as carrier concentration and synthetically determining electrical properties of the ITO TFTs. Interestingly, the ITO TFTs with a tITO of 9 nm exhibit the best performance and PBS stability, and typical electrical properties include a field-effect mobility (µFE) of 37.69 cm2/Vs, a Von of -2.3 V, a SS of 167.49 mV/decade, and an on-off current ratio over 107. This work paves the way for practical application of the ITO TFTs.

Fully transparent high performance thin film transistors with bilayer ITO/Al-Sn-Zn-O channel structures fabricated on glass substrate.

In this work, fully transparent high performance double-channel indium-tin-oxide/Al-Sn-Zn-O thin-film transistors (ITO/ATZO TFTs) are successfully fabricated on glass by radio frequency (RF) magnetron sputtering. The ITO layer acts as the bottom channel layer to increase the channel carrier concentration. The top ATZO channel layer, which is deposited via high oxygen partial pressure in the sputtering process, is useful to control the minimum off-state current. After annealing, the ITO/ATZO TFT demonstrates outstanding electrical performances, including a high ON/OFF current ratio (Ion/Ioff) of 3.5 × 108, a steep threshold swing (SS) of 142.2 mV/decade, a superior saturation mobility (µsat) of 246.0 cm2/Vs, and a threshold voltage VT of 0.5 V. The operation mechanisms for double-channel structures are also clarified.

Bi-layer Channel AZO/ZnO Thin Film Transistors Fabricated by Atomic Layer Deposition Technique.

This letter demonstrates bi-layer channel Al-doped ZnO/ZnO thin film transistors (AZO/ZnO TFTs) via atomic layer deposition process at a relatively low temperature. The effects of annealing in oxygen atmosphere at different temperatures have also been investigated. The ALD bi-layer channel AZO/ZnO TFTs annealed in dry O2 at 300 °C exhibit a low leakage current of 2.5 × 10-13A, I on/I off ratio of 1.4 × 107, subthreshold swing (SS) of 0.23 V/decade, and high transmittance. The enhanced performance obtained from the bi-layer channel AZO/ZnO TFT devices is explained by the inserted AZO front channel layer playing the role of the mobility booster.

Hydroxylation of 3-nitrotyrosine and its derivatives by gamma irradiation.

Radiation-induced hydroxylation of 3-nitrotyrosine (3-NY) and its derivatives in aqueous solution were investigated as a function of gamma-radiation dose. Irradiated 3-NY, 3-nitrotyrosine ethyl ester (3-NYE) and 3-NY containing peptide Gly-nitroTyr-Gly were separated and analyzed with reverse-phase HPLC and UV-Vis absorption spectroscopy. The structures of the hydroxylated products were confirmed by electrospray ionization mass spectrometry and (1)H-NMR spectrometry. The amounts of the hydroxylated products in irradiated 3-NY and Gly-nitroTyr-Gly solutions increased with increasing radiation dose. Tandem electrospray ionization mass spectrometry (ESI-Mass(2)) was performed to investigate the hydroxylation of peptide Gly-nitroTyr-Gly. These studies showed that the hydroxylation occurred at 3-NY residue. We also found that the identification of 3-NY hydroxylation in peptide could be identified by ion scanning for the specific immonium ion at m/z 197.0.