Memristive devices are promising candidates to emulate biological computing. However, the typical switching voltages (0.2-2 V) in previously described devices are much higher than the amplitude in ...biological counterparts. Here we demonstrate a type of diffusive memristor, fabricated from the protein nanowires harvested from the bacterium Geobacter sulfurreducens, that functions at the biological voltages of 40-100 mV. Memristive function at biological voltages is possible because the protein nanowires catalyze metallization. Artificial neurons built from these memristors not only function at biological action potentials (e.g., 100 mV, 1 ms) but also exhibit temporal integration close to that in biological neurons. The potential of using the memristor to directly process biosensing signals is also demonstrated.
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•A dual responsive ratiometric fluorescent probe for N2H4 and HSO3− was developed.•Different color changes based on different sensing mechanisms for N2H4 and HSO3−.•It has high ...selectivity and low detection limit for N2H4 and HSO3−.•Good recovery was achieved in industrial water for detecting N2H4 and HSO3−.•It has good biocompatibility.
Hydrazine and bisulfite are poisonous to the environment and human health, hence it is necessary to monitor hydrazine and bisulfite in the environment and living cells. In this study, we reported a smart fluorescent probe (CMCA) for discriminative detection of hydrazine and bisulfite. The single fluorescent probe can respond to hydrazine and bisulfite with two different sets of colorimetric and ratiometric fluorescence signals together with high selectivity, fast response and low detection limit. The discriminative sensing behaviors of the probe for hydrazine and bisulfite were ascribed to different reaction mechanisms, which were confirmed by 1H NMR and HR-MS spectra. The probe has been successfully used to discriminatively determine hydrazine and bisulfite in industrial wastewater with good recoveries. Furthermore, the probe was employed to visualize hydrazine and bisulfite in live cells from different fluorescence channels with good performance. Therefore, this probe has great potential applications for discriminative detection of hydrazine and bisulfite in the environment and living cells.
Background
The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first‐line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded ...significant results. However, it is not clear whether this treatment option is cost‐effective in China. The purpose of this study is to evaluate the cost‐effectiveness of tislelizumab plus GP for the first‐line treatment of R/M NPC from the perspective of the Chinese healthcare system.
Methods
A partitioned survival model with three discrete health states was constructed to evaluate the cost‐effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE‐309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality‐adjusted life years (QALYs), total cost, and incremental cost–benefit ratio (ICER).
Results
The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost‐effective at the willingness‐to‐pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD‐L1 expression had little impact on the ICER of this regimen.
Conclusion
In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first‐line treatment, is more cost‐effective than the GP regimen in China.
Lithospheric deformation of the Tibetan plateau is caused by subduction of the Indian (northward) and Asian (southward) plates. The effects of this interaction on inner reaches of the Asian ...continent, between the Tibetan plateau and the North China craton (NCC) for example, remain uncertain due to poor geophysical data coverage in northeastern Tibet (NE Tibet). We provide here detailed knowledge of the lithospheric structure beneath NE Tibet as determined from a dense broadband seismic profile traversing NE Tibet to the westernmost NCC. Receiver function imaging reveals several significant features, including a north-dipping intracrustal converter (NC), Moho offset/overlap beneath major fault zones, and a low velocity layer (LVL) in the middle-lower crust. The lithosphere–asthenosphere boundary (LAB) is clearly defined and appears as a south-dipping interface that runs continuously from the Alxa interior to the Qilian orogen. Interpretation of these observations, combined with other seismic evidence, implies that the NCC lithospheric mantle has been persistently underthrust beneath the Qilian orogen. This process forms the thick-skinned crustal accretionary wedges, which develop above a middle-lower intracrustal decollement. Our results provide further deep-geophysical constraints on the Cenozoic post-collisional evolution of the convergent boundary between NE Tibet and the NCC and help clarify the mechanism of plateau growth in this boundary area.
•Receiver functions image detailed lithospheric structure beneath NE Tibet.•Lithosphere–asthenosphere boundary dips southward continuously from Alxa to Qilian.•North China craton's lithospheric mantle may underthrust beneath the Qilian orogen.•Mantle underthrusting facilitates plateau growth in a manner of crustal wedges.•Our observations can be well accommodated in a model of stepwise mantle subduction.
Neuromorphic computing based on spikes offers great potential in highly efficient computing paradigms. Recently, several hardware implementations of spiking neural networks based on traditional ...complementary metal-oxide semiconductor technology or memristors have been developed. However, an interface (called an afferent nerve in biology) with the environment, which converts the analog signal from sensors into spikes in spiking neural networks, is yet to be demonstrated. Here we propose and experimentally demonstrate an artificial spiking afferent nerve based on highly reliable NbO
Mott memristors for the first time. The spiking frequency of the afferent nerve is proportional to the stimuli intensity before encountering noxiously high stimuli, and then starts to reduce the spiking frequency at an inflection point. Using this afferent nerve, we further build a power-free spiking mechanoreceptor system with a passive piezoelectric device as the tactile sensor. The experimental results indicate that our afferent nerve is promising for constructing self-aware neurorobotics in the future.
Threshold switches with Ag or Cu active metal species are volatile memristors (also termed diffusive memristors) featuring spontaneous rupture of conduction channels. The temporal dynamics of the ...conductance evolution is closely related to the electrochemical and diffusive dynamics of the active metals which could be modulated by electric field strength, biasing duration, temperature, and so on. Microscopic pictures by electron microscopy and quantitative thermodynamics modeling are examined to give insights into the underlying physics of the switching. Depending on the time scale of the relaxation process, such devices find a variety of novel applications in electronics, ranging from selector devices for memories to synaptic devices for neuromorphic computing.
Volatile threshold switches with Ag or Cu active metals in solid electrolytes feature electrical‐bias‐induced conduction channel formation and spontaneous rupture of the conduction channel upon cessation of the external bias, which shows unique delay and relaxation dynamics in conductance evolution and can be tuned for a variety of novel electronic applications, including selectors, synapses, neurons, true random number generators, etc.
The uplift mechanism and geodynamic model of the northeastern (NE) Tibetan Plateau remain controversial. Two competing models have been proposed for the uplift of the NE Tibetan Plateau, including ...crustal shortening through folding or thrust faulting and the middle-lower crustal flow model. Here, we applied the joint inversion of surface wave dispersions and receiver functions with P-wave velocity constraints on a dense linear broadband seismic array to obtain the Vs and Vp/Vs profiles of the crust and uppermost mantle across northeastern Tibet. The inversion yields robust structural images that show stark Vs and Vp/Vs jumps across the West Qinling fault from the Songpan-Ganzi and Kunlun-West Qinling terranes (south) to the Qilian and North China terranes (north). The results reveal that regional low-Vs/high-Vp/Vs anomalies present in the middle-to-lower crust, which may be the signature of viscous flow, are distinctly limited south of the West Qinling fault. In contrast, the imaged physical properties of the crust and mantle lithosphere north of this fault manifest a rigid pattern, which is inferred to be originated from the North China craton underthrust below the northern margin of the Tibetan plateau. Our seismic imaging indicates that the NE corner of the Tibetan Plateau does not currently serve as the flow channel of the ductile material from the central and northern Tibet.
•Joint inversion produces crustal Vs and Vp/Vs structures across NE Tibet.•Revealing a distinct lithospheric property contrast across the West Qinling fault.•North of the West Qinling fault is manifested as a rigid pattern.•Inferred crustal flow is limited south of the West Qinling fault.
This work aimed to investigate tumor-infiltrating immune cells (TIICs) and immune-associated genes in the tumor microenvironment of osteosarcoma. An algorithm known as ESTIMATE was applied for immune ...score assessment, and osteosarcoma cases were assigned to the high and low immune score groups. Immune-associated genes between these groups were compared, and an optimal immune-related risk model was built by Cox regression analyses. The deconvolution algorithm (referred to as CIBERSORT) was applied to assess 22 TIICs for their amounts in the osteosarcoma microenvironment. Osteosarcoma cases with high immune score had significantly improved outcome (P<0.01). The proportions of naive B cells and M0 macrophages were significantly lower in high immune score tissues compared with the low immune score group (P<0.05), while the amounts of M1 macrophages, M2 macrophages, and resting dendritic cells were significantly higher (P<0.05). Important immune-associated genes were determined to generate a prognostic model by Cox regression analysis. Interestingly, cases with high risk score had poor outcome (P<0.01). The areas under the curve (AUC) for the risk model in predicting 1, 3 and 5-year survival were 0.634, 0.781, and 0.809, respectively. Gene set enrichment analysis suggested immunosuppression in high-risk osteosarcoma patients, in association with poor outcome.
Monitoring sulfur dioxide (SO2) derivatives in environment is of great significance due to their harmful effects to the environment and human health. In this study, a fluorescent probe (CZBT) for SO2 ...derivatives was prepared from 9-ethyl-9H-carbazole-3,6-dicarboxaldehyde and 2-methyl-benzothiazolium, which displayed a noticeable color change from yellow to colorless along with a remarkable fluorescence change from yellow to blue in response to HSO3−. The probe could quantitatively determine the concentration of HSO3− with excellent selectivity, high sensitivity and low limit of detection. 1H NMR and HR-MS spectra demonstrated that a selective 1, 4-nucleophilic addition occurred on the bridge double bond in CZBT. The probe was successfully used to determine the SO2 derivatives in several real water samples with good recovery. Furthermore, the probe was employed for monitoring the level of intracellular HSO3− in HeLa (human cervical cancer) cells by fluorescence imaging. These results indicated that CZBT has a good capability for monitoring SO2 derivatives in environment and living cells.
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•A colorimetric and ratiometric fluorescent probe has been developed for the specific detection of SO2 derivatives.•The probe can visualize environmentally harmful SO2 derivatives with low limit of detection (28nM).•The probe showed good recovery in the determination of SO2 derivatives in industrial wastewater and snow-broth.•The probe has been employed to visualize trace SO2 derivatives in living cells.
Experimental demonstration of resistive neural networks has been the recent focus of hardware implementation of neuromorphic computing. Capacitive neural networks, which call for novel building ...blocks, provide an alternative physical embodiment of neural networks featuring a lower static power and a better emulation of neural functionalities. Here, we develop neuro-transistors by integrating dynamic pseudo-memcapacitors as the gates of transistors to produce electronic analogs of the soma and axon of a neuron, with "leaky integrate-and-fire" dynamics augmented by a signal gain on the output. Paired with non-volatile pseudo-memcapacitive synapses, a Hebbian-like learning mechanism is implemented in a capacitive switching network, leading to the observed associative learning. A prototypical fully integrated capacitive neural network is built and used to classify inputs of signals.
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