Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also ...infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.
Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant cancers with high inter- and intra-tumor heterogeneity. A central common signaling mechanism in cancer is proline-directed ...phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 is prevalently overexpressed in human cancers including ~70% of HCC, and promotes tumorigenesis by activating multiple cancer-driving pathways. However, it was challenging to evaluate the significance of targeting Pin1 in cancer treatment until the recent identification of all-trans retinoic acid (ATRA) as a Pin1 inhibitor. Here we systematically investigate functions of Pin1 and its inhibitor ATRA in the development and treatment of HCC. Pin1 knockdown potently inhibited HCC cell proliferation and tumor growth in mice. ATRA-induced Pin1 degradation inhibited the growth of HCC cells, although at a higher IC50 as compared with breast cancer cells, likely due to more active ATRA metabolism in liver cells. Indeed, inhibition of ATRA metabolism enhanced the sensitivity of HCC cells to ATRA. Moreover, slow-releasing ATRA potently and dose-dependently inhibited HCC growth in mice. Finally, chemical or genetic Pin1 ablation blocked multiple cancer-driving pathways simultaneously in HCC cells. Thus, targeting Pin1 offers a promising therapeutic approach to simultaneously stop multiple cancer-driving pathways in HCC.
This letter proposes a new organic trench structure which can enhance the endurance of polycrystalline silicon thin film transistors (TFTs) under mechanical bending stress. It compares conventional ...structure TFTs to devices with an organic trench to examine reliability after undergoing 100,000 iterations of channel width-axis (100,000'WC) compression at R = 2mm. Due to the low Young's modulus of organic materials, stress while undergoing bending strain is desorbed to the buffer layer, which can lower the overall stress in TFTs. Furthermore, an optimal location and ideal length for such an organic trench is evaluated by mechanical bending simulation.
Highlights • Tofacitinib is an oral Janus kinase inhibitor. • Tofacitinib showed superior efficacy vs placebo in Asian patients with psoriasis. • No unexpected safety findings were observed in Asian ...patients vs global studies.
This paper investigates material modifications induced by cosputtering indium-tin oxide (ITO) with gadolinium (Gd) at two different power levels. In addition, resistance switching (RS) properties ...were also verified for use as an insulator in resistive random access memory (RRAM). Comparison of scanning electron microscope (SEM) measurements for the two different cosputtering powers indicated significant changes of the ITO surface. Transparency was also verified by an N&K analyzer measurement, with results indicating a constant in transparency induced by the lower power Gd doping, indicating potential for transparent applications. Furthermore, the mole fraction ratio defined by X-ray photoelectron spectroscopy reveals a Gd 2 O 3 peak, a likely reason for the ITO thin film becoming less conductive. This ITO/Gd:ITO/TiN RRAM can exhibit stable and robust RS characteristics at a lower forming voltage. In addition, lower operating voltages, including both SET and RESET voltages, can be obtained. Reliability tests including endurance and retention were carried out to confirm its RS stability. The RS mechanism of this ITO/Gd:ITO/TiN device was also investigated with the current-voltage (<inline-formula> <tex-math notation="LaTeX">{I} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">{V} </tex-math></inline-formula>) fitting method. Moreover, temperature effects were also applied to verify the high-resistance state (HRS) mechanism. Finally, a conduction model was proposed to clarify the RS characteristics and confirm that the ITO/Gd:ITO/TiN device is appropriate for data storage.
This letter investigates flexible polycrystalline silicon thin film transistor performance variation due to different buffer layer thicknesses. In flexible electronics, thermal expansion stress ...during device fabrication is inevitable. A thicker SiO 2 buffer demonstrates better endurance to thermal expansion stress from the polyimide substrate during device annealing. However, if the SiO 2 buffer thickness is above a critical point, its weak heat dissipation capability causes the optimal ELA crystallization condition to shift. A thermal expansion stress simulation and TEM photos were utilized to verify performance variation. Furthermore, a similar trend was observed in electrical characteristics after negative bias temperature instability.
We have previously investigated the automatic current compliance property for indium tin oxide (ITO) resistance random access memory (RRAM). Traditionally, for the purpose of protecting RRAM, it is ...necessary to set equipment current compliance during the set and forming processes of RRAM devices. ITO RRAM devices, however, have an intrinsic capability to limit their current. This letter examines this ITO RRAM current compliance in depth by applying a varied stop-voltage measurement method, where different negative stop voltages were adopted to manipulate oxygen ions. Combined with material analysis and conduction current fitting, a model was established.
Background: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. ...Methods: Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. Results: The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, p < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. Conclusions: For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.
In this experiment, the electrical performance of zinc oxide based-resistive random access memory (RRAM) is successfully improved by using annealing in ammonia hydroxide solution at low-temperature ...and high pressure to complete ammonium-doped ZnO based-RRAM. The results of material analysis indicate that using CO 2 as ammonia hydroxide carrier during the annealing process leads to the reduction in dangling bond density. This can be clearly observed in the decrease in breakdown voltage during the forming process and a lower operating current during operation. Furthermore, in this ammonium-doped ZnO based-RRAM, we study the molecular doping of NH 3 in ZnO, where the endurance and retention properties are improved as well. These improvements can be attributed to the higher concentration of nitrogen in the switching layer, which can effectively control the active oxygen ions during the operation process.
In this study, an oxidation treatment technique suitable for the material and electronic device applications proceeding at low temperature (only 80 °C) and high pressure (3000 psi) utilizing a carbon ...dioxide (CO2) supercritical fluid (SCF), also known as scCO2, which is supplemented with water molecules, is reported. To demonstrate the possible effects on material and devices for the proposed SCF treatment, an amorphous germanium–sulfur (GeS) thin film and a GeS‐based resistance random access memory (RRAM) device are prepared. After the SCF treatment, electrical measurements confirm that the GeS‐based RRAM device exhibits a lower forming voltage, more stable resistance switching characteristics, and higher concentration distributions of high and low resistance states when compared to the device without SCF treatment. As for the material effects, both chemical and physical properties are examined based on material analyses results. It is concluded that the original amorphous GeS thin film transforms to a polycrystallized GeO film, confirmed by a reaction model for the SCF treatment illustrating possible oxidation and crystallization effects induced by this SCF treatment. This water‐enhanced scCO2 SCF treatment technique, thus, shows its capability as a feasible synthetic method for material modification as well as suitability for device level applications.
In this study, a supercritical fluid (SCF) of carbon dioxide supplemented with water is utilized in a treatment technique, which is applied to germanium‐sulfur‐based (GeS‐based) thin film, and the electronic device is investigated. Both surface chemical and physical properties are examined based on electrical measurements and material analyses to find possible reacting mechanisms arising from the proposed SCF treatment.
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