The clinical regimens and cell membrane camouflaged nanodrug delivery systems in hematologic malignancies treatment

Hematologic malignancies (HMs), also referred to as hematological or blood cancers, pose significant threats to patients as they impact the blood, bone marrow, and lymphatic system. Despite significant clinical strategies using chemotherapy, radiotherapy, stem cell transplantation, targeted molecular therapy, or immunotherapy, the five-year overall survival of patients with HMs is still low. Fortunately, recent studies demonstrate that the nanodrug delivery system holds the potential to address these challenges and foster effective anti-HMs with precise treatment. In particular, cell membrane camouflaged nanodrug offers enhanced drug targeting, reduced toxicity and side effects, and/or improved immune response to HMs. This review firstly introduces the merits and demerits of clinical strategies in HMs treatment, and then summarizes the types, advantages, and disadvantages of current nanocarriers helping drug delivery in HMs treatment. Furthermore, the types, functions, and mechanisms of cell membrane fragments that help nanodrugs specifically targeted to and accumulate in HM lesions are introduced in detail. Finally, suggestions are given about their clinical translation and future designs on the surface of nanodrugs with multiple functions to improve therapeutic efficiency for cancers

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis

12.1 terabit/second data center interconnects using O-band coherent transmission with QD-MLL frequency combs.

Most current Data Center Interconnects (DCI) use intensity modulation direct detection (IMDD) configurations due to their low complexity and cost. However, significant scaling challenges allow coherent solutions to become contenders in these short reach applications. We present an O-band coherent optical fiber transmission system based on Quantum Dot-Mode Locked Lasers (QD-MLLs) using two independent free-running comb lasers, one each for the carrier and the Local Oscillator (LO). Using a comb-to-comb configuration, we demonstrate a 10 km single mode fiber, O-band, coherent, heterodyne, 12.1 Tbps system operating at 0.47 Tbps/λ using 26 λs. We used fewer comb lines (26 λs), faster symbol rate (56 GBaud) and higher constellation cardinality (32 QAM) relative to the highest capacity C-band systems reported to date. Through design, analysis, and experimentation, we quantify the optimum comb line spacing for this use case. We compare potential configurations for increasing data center interconnect capacities whilst reducing power consumption, complexity, and cost

Simulation of Electrochemical Impedance Spectra of Solid Oxide Fuel Cells Using Transient Physical Models

A general electrochemical impedance spectroscopy ͑EIS͒ modeling approach by directly solving a one-dimensional transient model based on physical conservation laws was applied for simulating EIS spectra of an anode-supported solid oxide fuel cell ͑SOFC͒ button cell consisting of Ni-yttria-stabilized zirconia ͉Ni-scandia-stabilized zirconia ͑ScSZ͉͒ScSZ͉lanthanum strontium manganate ͑LSM͒-ScSZ multiple layers. The transient SOFC model has been solved for imposed sinusoidal voltage perturbations at different frequencies. The results have then been transformed into EIS spectra. Six parameters had to be tuned ͑three for the cathode and three for the anode͒ and have been estimated using data from a symmetric cathode cell and from a button cell. The experimental and simulated EIS spectra were in good agreement for a range of temperatures ͑750-850°C͒, of feed compositions ͑mixture of H 2 /H 2 O/N 2 ͒, and of oxidants ͑air and oxygen͒. This approach can help in interpreting EIS spectra, as illustrated by identifying the contribution of transport limitation. Fuel cell electrochemical systems are usually complex and are governed by coupled physicochemical processes such as chemical and electrochemical reactions, charge transport, and mass transport. 1,2 Because polarization curves can only provide a general description of the cell performance, electrochemical impedance spectroscopy ͑EIS͒ has become widely used in fuel cell research and development because it involves a relatively simple electrical measurement that gives detailed information about the fuel cell system, from mass-transport properties, chemical reaction rates, and dielectric properties to defects, microstructure, compositional influences, etc. 3 In this dynamic technique, usually a voltage perturbation is applied to a system and the amplitude and phase shift of the resulting current response are measured. Measurements can be conducted over a wide range of frequencies, resulting in the construction of impedance spectra. 5 Although the approach is useful and quite powerful, it often has limitations such as: 1. The approach can lead to ambiguities in data interpretations because the equivalent circuits are seldom unique except for only the simplest circuits. An equivalent circuit involving several circuit elements could often be rearranged in various configurations while still yielding the same impedance. 2. Detailed physical and chemical processes in the system cannot be predicted by equivalent-circuit models. For instance, the effects of current distributions and concentration distributions cannot be taken into account when interpreting data from equivalent-circuit models. 3. The measured system could only be approximated by circuit elements when assuming linear response of the system. The impedance is supposed to be independent of the amplitude of the applied signals. However, the electrochemical system could be highly nonlinear, especially for sinusoidal perturbations with high amplitudes. It was suggested that nonlinear EIS ͑NLEIS͒ measurements have several potential advantages. To investigate solid oxide fuel cell ͑SOFC͒ electrode reaction kinetics, Miterdorfer and Gauckler 7-9 used a state-space model ͑SSM͒, which is widely used in control theory for solving complex differential equations. Bieberle and Gauckler 5 studied in depth elementary electrochemical reactions in SOFC anode by both experimental and SSM approaches. To simulate the electrochemical impedance spectra, the models were solved directly through the SSM approach. Bessler 10 presented a computational method for simulating EIS spectra based on transient numerical simulations of the reaction system. The impedance was then calculated in the time domain from the simulated periodic response of the system, maintaining its full nonlinear response. This method has been further validated by detailed modeling studies on SOFC EIS spectra achieved from gas-transport processes. 11 Gewies et al. 12 also applied this method on Ni/yttria-stabilized zirconia ͑YSZ͒ cermet anodes. Zhu and Kee 13 developed a time-accurate model to analyze EIS spectra in anode-supported button cells with internal methane reforming. This model represented significant advantages regarding physical conservation laws, porous media transport within the electrode, and heterogeneous chemistry reactions mechanisms, all of those being solved in the time domain. However, the spatial variations of ion and electron transport throughout the electrode structures were not considered. In this paper, a general approach for EIS spectra simulation is applied by solving a comprehensive set of coupled transient models based on physical conservation laws. This simulation approach is illustrated by considering a transient model of an anode-supported SOFC button cell consisting of Ni-YSZ͉Ni-scandia-stabilized zirconia ͑ScSZ͉͒ScSZ͉LSM-ScSZ multiple layers. The simulation results of the EIS spectra were then compared to the measured EIS spectra under various conditions to prove the validity of both the transient model and the EIS simulation approach. Experimental Testing cell.-The anode-supported SOFC button cell used in this study consisted of a Ni/YSZ anode support layer ͑680 m͒, a Ni/ScSZ anode active interlayer ͑15 m͒, a ScSZ thin-film electrolyte layer ͑20 m͒, and a lanthanum strontium manganate ͑LSM͒/ ScSZ cathode layer ͑15 m͒. 14,1

Subthalamic nucleus dynamics track microlesion effect in Parkinson’s disease

Parkinson’s Disease (PD) is characterized by the temporary alleviation of motor symptoms following electrode implantation (or nucleus destruction), known as the microlesion effect (MLE). Electrophysiological studies have explored different PD stages, but understanding electrophysiological characteristics during the MLE period remains unclear. The objective was to examine the characteristics of local field potential (LFP) signals in the subthalamic nucleus (STN) during the hyperacute period following implantation (within 2 days) and 1 month post-implantation. 15 patients diagnosed with PD were enrolled in this observational study, with seven simultaneous recordings of bilateral STN-LFP signals using wireless sensing technology from an implantable pulse generator. Recordings were made in both on and off medication states over 1 month after implantation. We used a method to parameterize the neuronal power spectrum to separate periodic oscillatory and aperiodic components effectively. Our results showed that beta power exhibited a significant increase in the off medication state 1 month after implantation, compared to the postoperative hyperacute period. Notably, this elevation was effectively attenuated by levodopa administration. Furthermore, both the exponents and offsets displayed a decrease at 1 month postoperatively when compared to the hyperacute postoperative period. Remarkably, levodopa medication exerted a modulatory effect on these aperiodic parameters, restoring them back to levels observed during the hyperacute period. Our findings suggest that both periodic and aperiodic components partially capture distinct electrophysiological characteristics during the MLE. It is crucial to adequately evaluate such discrepancies when exploring the mechanisms of MLE and optimizing adaptive stimulus protocols

Dissociable Modulation of Overt Visual Attention in Valence and Arousal Revealed by Topology of Scan Path

Emotional stimuli have evolutionary significance for the survival of organisms; therefore, they are attention-grabbing and are processed preferentially. The neural underpinnings of two principle emotional dimensions in affective space, valence (degree of pleasantness) and arousal (intensity of evoked emotion), have been shown to be dissociable in the olfactory, gustatory and memory systems. However, the separable roles of valence and arousal in scene perception are poorly understood. In this study, we asked how these two emotional dimensions modulate overt visual attention. Twenty-two healthy volunteers freely viewed images from the International Affective Picture System (IAPS) that were graded for affective levels of valence and arousal (high, medium, and low). Subjects' heads were immobilized and eye movements were recorded by camera to track overt shifts of visual attention. Algebraic graph-based approaches were introduced to model scan paths as weighted undirected path graphs, generating global topology metrics that characterize the algebraic connectivity of scan paths. Our data suggest that human subjects show different scanning patterns to stimuli with different affective ratings. Valence salient stimuli (with neutral arousal) elicited faster and larger shifts of attention, while arousal salient stimuli (with neutral valence) elicited local scanning, dense attention allocation and deep processing. Furthermore, our model revealed that the modulatory effect of valence was linearly related to the valence level, whereas the relation between the modulatory effect and the level of arousal was nonlinear. Hence, visual attention seems to be modulated by mechanisms that are separate for valence and arousal