Aicardi-Goutières syndrome (AGS) is characterized by progressive neurologic decline, cerebral calcification, and variable manifestations of autoimmunity. Seven subtypes of AGS have been defined and aberrant activation of the type I interferon system is a common theme among these conditions. We describe a 13-year-old boy who presented with an unusual constellation of psoriasis, interstitial lung disease (ILD), and pulmonary hypertension in addition to cerebral calcifications and glomerulonephritis. He was found to have late-onset AGS due to a gain-of-function mutation in IFIH1 and over-activation of the type I interferon pathway was confirmed by RNA sequencing. The majority of his clinical manifestations, including ILD, psoriasis and renal disease improved markedly after treatment with the combination of corticosteroids, cyclophosphamide, and the Janus-kinase inhibitor tofacitinib. This case extends the clinical spectrum of AGS and suggests the need for lung disease screening in patients with AGS.

The coexisting oscillations are observed with a memcapacitor‐based circuit that consists of two linear inductors, two linear resistors, and an active nonlinear charge‐controlled memcapacitor. We analyze the dynamics of this circuit and find that it owns an infinite number of equilibrium points and coexisting attractors, which means extreme multistability arises. Furthermore, we also show the stability of the infinite many equilibria and analyze the coexistence of fix point, limit cycle, and chaotic attractor in detail. Finally, an experimental result of the proposed oscillator via an analog electronic circuit is given.

Drug-target binding affinity (DTA) prediction can accelerate the drug screening process, and deep learning techniques have been used in all facets of drug research. Affinity prediction based on deep learning methods has proven crucial to drug discovery, design, and reuse. Among these, the sequence-based approach using 1D sequences of drugs and targets as inputs typically results in the loss of structural information, whereas the structure-based method frequently results in increased computing costs due to the intricate structure of the molecule graph. We propose a sequential multifeature fusion method (SMFF-DTA) to achieve efficient and accurate prediction. SMFF-DTA uses sequential methods to represent the structural information and physicochemical properties of drugs and targets and introduces multiple attention blocks to capture interaction features closely. As demonstrated by our extensive studies, SMFF-DTA outperforms the other methods in terms of various metrics, showing its advantages and effectiveness as a drug-target binding affinity predictor.

Background: Cryptococcal meningitis (CM) is a significant global health issue, particularly affecting individuals with HIV. Amphotericin B (AmB) serves as the cornerstone treatment for CM; however, its clinical application is restricted due to limited penetration of the blood–brain barrier and associated nephrotoxicity.Objective: This study investigates the use of exosomes derived from induced pluripotent stem cells (iPSC-Exos) as carriers for AmB in treating CM, aiming to enhance therapeutic efficacy and safety and reduce AmB toxicity.Methods: Exosomes were extracted from iPSC culture supernatants using ultrafiltration and ultracentrifugation. Their morphology and size were analyzed using transmission electron microscopy (TEM) and nanoparticle flow cytometry (nFCM). Purity was confirmed by Western blotting for markers CD9, CD63, and TSG101. AmB was loaded into iPSC-Exos using a co-incubation method. The cytotoxicity of the iPSC-Exo/AmB complex was evaluated on HEK 293 T and RAW264.7 cells using the CCK-8 assay, while apoptosis was assessed using live/dead cell staining and flow cytometry. The hemolytic effects were tested using rabbit red blood cells. In a C57BL/6 J mouse model of cryptococcal infection, treatment groups (AmB, iPSC-Exo/AmB, and iPSC-Exo) were administered corresponding drugs, with blood and brain samples collected for analysis. The minimum inhibitory concentration (MIC) of iPSC-Exo/AmB and conventional AmB against Cryptococcus was determined.Results: The iPSC-Exo/AmB complex exhibited reduced cytotoxicity in vitro and decreased AmB-induced renal and hepatic toxicity in vivo. Its MIC against Cryptococcus was over eight times lower than conventional AmB, significantly reducing fungal burden in the mouse brain and lowering serum inflammatory factors.Conclusion: The iPSC-Exo/AmB complex is a promising therapeutic strategy that enhances AmB efficacy while reducing toxicity, offering new hope for treating CM and other refractory fungal infections of the central nervous system.

Memristor and memcapacitor are new nonlinear devices with memory. We present a novel memcapacitor model that has the capability of capturing the behavior of a memcapacitor. Based on this model we also design a chaotic oscillator circuit that contains a HP memristor and the memcapacitor model for generating good pseudorandom sequences. Its dynamic behaviors, including equilibrium points, stability, and bifurcation characteristics, are analyzed in detail. It is found that the proposed oscillator can exhibit some complex phenomena, such as chaos, hyperchaos, coexisting attractors, abrupt chaos, and some novel bifurcations. Moreover, a scheme for digitally realizing this oscillator is provided by using the digital signal processor (DSP) technology. Then the random characteristics of the chaotic binary sequences generated from the oscillator are tested via the test suit of National Institute of Standards and Technology (NIST). The tested randomness definitely reaches the standards of NIST and is better than that of the well-known Lorenz system.

Oxygen reduction reaction (ORR) not only needs the excellent electrode materials, but also requires quick mass transfer of dissolved oxygen. To strengthen the ORR and O₂⁻ oxidation desulfurization, pressurized water electrolysis was carried out in this work. The results showed that the desulfurization ratio increased with increasing pressure, indicating that the pressure has strengthened the O₂⁻ generation. As expected, the ORR initial potential shifted from −0.034 V to −0.030 V with increasing pressure from 0.1Mpa to 2Mpa. The peak current, the limit current density and the peak integral area all increased with increasing pressure. On the other hand, the reduction in solution resistance (R_s) and reaction resistance (R_ct) further verified that the pressure can strengthen the transfer of dissolved oxygen and the ORR dynamics. More importantly, the pressure has improved O₂⁻ generated potential in a large parameter window (the width of the metastable zone, the difference between the initial potential and the peak potential of the ORR). The pressure could enhance the O₂⁻ formation, and improve the desulfurization process.