In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

A three-terminal memristor with an ultrasmall footprint of only 0.07 μm2 and critical dimensions of 70 nm × 10 nm × 6 nm is introduced. The device\'s feature is the presence of a gate contact, which enables two operation modes: either tuning the set voltage or directly inducing a resistance change. In I-V mode, we demonstrate that by changing the gate voltages between ±1 V one can shift the set voltage by 69%. In pulsing mode, we show that resistance change can be triggered by a gate pulse. Furthermore, we tested the device endurance under a 1 kHz operation. In an experiment with 2.6 million voltage pulses, we found two distinct resistance states. The device response to a pseudorandom bit sequence displays an open eye diagram and a success ratio of 97%. Our results suggest that this device concept is a promising candidate for a variety of applications ranging from Internet-of-Things to neuromorphic computing.

OBJECTIVE: Beam delivery latency in respiratory-gated particle therapy systems is a crucial issue to dose delivery accuracy. The aim of this study is to develop a multi-channel signal acquisition platform for investigating gating latencies occurring within RPM respiratory gating system (Varian, USA) and ProBeam proton treatment system (Varian, USA) individually.
METHODS: The multi-channel signal acquisition platform consisted of several electronic components, including a string position sensor for target motion detection, a photodiode for proton beam sensing, an interfacing board for accessing the trigger signal between the respiratory gating system and the proton treatment system, a signal acquisition device for sampling and synchronizing signals from the aforementioned components, and a laptop for controlling the signal acquisition device and data storage. RPM system latencies were determined by comparing the expected gating phases extracted from the motion signal with the trigger signal\'s state turning points. ProBeam system latencies were assessed by comparing the state turning points of the trigger signal with the beam signal. The total beam delivery latencies were calculated as the sum of delays in the respiratory gating system and the cyclotron proton treatment system. During latency measurements, simulated sinusoidal motion were applied at different amplitudes and periods for complete beam delivery latency evaluation under different breathing patterns. Each breathing pattern was repeated 30 times for statistical analysis.
RESULTS: The measured gating ON/OFF latencies in the RPM system were found to be 104.20 ± 13.64 ms and 113.60 ± 14.98 ms, respectively. The measured gating ON/OFF delays in the ProBeam system were 108.29 ± 0.85 ms and 1.20 ± 0.04 ms, respectively. The total beam ON/OFF latencies were determined to be 212.50 ± 13.64 ms and 114.80 ± 14.98 ms.
CONCLUSIONS: With the developed multi-channel signal acquisition platform, it was able to investigate the gating lags happened in both the respiratory gating system and the proton treatment system. The resolution of the platform is enough to distinguish the delays at the millisecond time level. Both the respiratory gating system and the proton treatment system made contributions to gating latency. Both systems contributed nearly equally to the total beam ON latency, with approximately 100 ms. In contrast, the respiratory gating system was the dominant contributor to the total beam OFF latency.

Ligand-gated ion channels are a large category of essential ion channels, modulating their state by binding to specific ligands to allow ions to pass through the cell membrane. Purinergic ligand-gated ion channel receptors (P2XRs) and acid-sensitive ion channels (ASICs) are representative members of trimeric ligand-gated ion channel. Recent studies have shown that structural differences in the intracellular domain of P2XRs may determine the desensitization process. The lateral fenestrations of P2XRs potentially serve as a pathway for ion conductance and play a decisive role in ion selectivity. Phosphorylation of numerous amino acid residues in the P2XRs are involved in regulating the activity of ion channels. Additionally, the P2XRs interact with other ligand-gated ion channels including N-methyl-D-aspartate receptors, γ-aminobutyric acid receptors, 5-hydroxytryptamin receptors and nicotinic acetylcholine receptors, mediating physiological processes such as synaptic plasticity. Conformational changes in the intracellular domain of the ASICs expose binding sites of intracellular signal partners, facilitating metabolic signal transduction. Amino acids such as Val16, Ser17, Ile18, Gln19 and Ala20 in the ASICs participate in channel opening and membrane expression. ASICs can also bind to intracellular proteins, such as CIPP and p11, to regulate channel function. Many phosphorylation sites at the C-terminus and N-terminus of ASICs are involved in the regulation of receptors. Furthermore, ASICs are involved in various physiological and pathophysiological processes, which include pain, ischemic stroke, psychiatric disorders, and neurodegenerative disease. In this article, we review the roles of the intracellular domains of these trimeric ligand-gated ion channels in channel gating as well as their physiological and pathological functions, in order to provide new insights into the discovery of related drugs.
配体门控离子通道是一大类重要的膜蛋白。嘌呤能配体门控离子通道（P2X）受体和酸敏感离子通道（ASIC）是三聚体配体门控离子通道的代表成员。P2X受体胞内区域的结构差异可影响脱敏过程，胞内区域的侧窗可作为离子渗透到细胞内的潜在路径并对离子选择性有决定作用，胞内区域众多氨基酸残基的磷酸化参与调节离子通道的活性。此外，胞内区域与N-甲基-D-天冬氨酸受体、γ-氨基丁酸受体、5-羟色胺受体和N型乙酰胆碱受体等其他配体门控离子通道存在相互作用并介导突触可塑性等病理生理过程。ASIC胞内区域的构象变化会暴露胞内信号分子的结合位点并促进代谢信号转导，胞内区域的氨基酸Val16、Ser17、Ile18、Gln19和Ala20可以调节通道上膜表达并参与门控过程，胞内区域的PDZ结构域可与多种细胞内蛋白质如骨架蛋白CIPP和p11相互作用从而参与对受体的调控，胞内区域羧基端和氨基端的众多磷酸化位点参与了对受体的调控。此外，胞内区域参与了疼痛、缺血性脑卒中、精神疾病、神经退行性疾病等多种病理生理过程。本文综述了P2X受体和ASIC胞内区域的结构以及在调节离子通道的门控特性和病理生理功能中的作用，以期为三聚体配体门控离子通道的药物研发提供新思路。.

One of the core challenges of deep learning in medical image analysis is data insufficiency, especially for 3D brain imaging, which may lead to model over-fitting and poor generalization. Regularization strategies such as knowledge distillation are powerful tools to mitigate the issue by penalizing predictive distributions and introducing additional knowledge to reinforce the training process. In this paper, we revisit knowledge distillation as a regularization paradigm by penalizing attentive output distributions and intermediate representations. In particular, we propose a Confidence Regularized Knowledge Distillation (CReg-KD) framework, which adaptively transfers knowledge for distillation in light of knowledge confidence. Two strategies are advocated to regularize the global and local dependencies between teacher and student knowledge. In detail, a gated distillation mechanism is proposed to soften the transferred knowledge globally by utilizing the teacher loss as a confidence score. Moreover, the intermediate representations are attentively and locally refined with key semantic context to mimic meaningful features. To demonstrate the superiority of our proposed framework, we evaluated the framework on two brain imaging analysis tasks (i.e. Alzheimer\'s Disease classification and brain age estimation based on T1-weighted MRI) on the Alzheimer\'s Disease Neuroimaging Initiative dataset including 902 subjects and a cohort of 3655 subjects from 4 public datasets. Extensive experimental results show that CReg-KD achieves consistent improvements over the baseline teacher model and outperforms other state-of-the-art knowledge distillation approaches, manifesting that CReg-KD as a powerful medical image analysis tool in terms of both promising prediction performance and generalizability.

Bats frequently inhabit caves and other subterranean habitats and play a critical role in subterranean food webs. With escalating threats to subterranean ecosystems, identifying the most effective measures to protect subterranean-roosting bats is critical. We conducted a meta-analysis to evaluate the effectiveness of conservation and management interventions for subterranean-roosting bats. We used network analyses to determine to what extent interventions for bats overlap those used for other subterranean taxa. We conducted our analyses with data extracted from 345 papers recommending a total of 910 conservation interventions. Gating of roost entrances was applied to preserve bat populations in 21 studies, but its effectiveness was unclear. Habitat restoration and disturbance reduction positively affected bat populations and bat behavior, respectively, in ≤4 studies. Decontamination was assessed in 2 studies and positively affected bat populations, particularly in studies focused on reducing fungal spores associated with white-nose syndrome in North America. Monitoring of bat populations as an effective conservation strategy was unclear and infrequently tested. Only 4% of bat studies simultaneously considered other subterranean organisms. However, effective interventions for bat conservation had similarities with all other organisms. If other subterranean organisms are considered when applying interventions to conserve bats, they might also benefit.
Conservación eficiente de murciélagos subterráneos Resumen Es común que los murciélagos habiten en cuevas y otros hábitats subterráneos y contribuyan a las redes alimenticias bajo tierra. Ya que estos ecosistemas cada vez se enfrentan a más amenazas, es importante identificar las medidas más efectivas para proteger a los murciélagos subterráneos. Realizamos un metaanálisis para evaluar la eficiencia de la conservación y las intervenciones de manejo para estos mamíferos. Usamos un análisis de redes para determinar el grado al que las intervenciones en pro de los murciélagos se traslapan con aquellas usadas para otros taxones subterráneos. Realizamos nuestros análisis con datos extraídos de 345 artículos que recomendaban 910 intervenciones de conservación. Se aplicó la colocación de compuertas en la entrada de los dormideros para conservar la población de murciélagos en 21 estudios, pero no quedó clara su efectividad. La restauración del hábitat y la reducción de las perturbaciones afectaron, respectivamente, a las poblaciones y al comportamiento de los murciélagos en ≤ 4 cuatro estudios. Se evaluó a la desinfección en dos estudios y ésta tuvo un efecto positivo sobre las poblaciones, particularmente en los estudios enfocados en la reducción de esporas micóticas asociadas con el síndrome de nariz blanca en América del Norte. La eficiencia del monitoreo de las poblaciones de murciélagos como una estrategia de conservación no fue clara y casi nunca se evaluó. Sólo el 4% de los estudios sobre murciélagos consideró simultáneamente a otros organismos subterráneos. Sin embargo, las intervenciones eficientes para la conservación de murciélagos tuvieron similitudes con las de todos los demás organismos. Otros organismos pueden beneficiarse si se les considera cuando se aplican las intervenciones para conservar a los murciélagos.
【摘要】 蝙蝠经常栖息在山洞及其他地下(洞穴)栖息地, 并在地下食物网中发挥着关键作用。随着地下生态系统面临的威胁不断加剧, 确定对地下栖息的蝙蝠最有效的保护措施至关重要。本研究通过荟萃分析评估了对地下栖息蝙蝠的保护和管理干预措施的有效性。我们使用网络分析, 确定了对蝙蝠的干预措施在多大程度上与对其他地下类群的干预措施相重合。我们分析了来自345篇论文的数据, 并建议开展910项保护干预措施。其中, 有21项研究对蝙蝠地下栖息地入口进行了封堵以保护蝙蝠种群, 但效果并不明显。在 ≤ 4项研究中, 栖息地恢复和减少干扰分别对蝙蝠种群数量和行为产生了积极影响。2项研究评估发现去除污染对蝙蝠种群产生了积极的影响, 特别是减少与北美白鼻综合症有关的真菌孢子的研究。此外, 对蝙蝠种群监测的保护策略有效性并不明确, 也很少得到检验。只有4%的蝙蝠研究同时考虑其他地下生物。然而, 蝙蝠与所有其他生物的有效干预措施都存在相似之处。如果在采取干预措施保护蝙蝠的同时考虑其他地下生物, 则这些物种也可能从中受益。【翻译:胡怡思;审校:聂永刚】.

Innovative optoelectronics are expected to play more important role in clinical diagnosis. In this study, on the basis of sensitive gating effect by in situ enzymatic functionalization of semiconductors, a novel organic photoelectrochemical transistor (OPECT) detection of serum alkaline phosphatase (ALP) level was demonstrated. Specifically, the OPECT detection operates upon the ALP-catalyzed hydrolysis of sodium thiophosphate to yield hydrogen sulfide (H2S), which could in situ generate CdS on the TiO2 electrode in the presence of Cd2+ cations. Correlated to the ALP level, the CdS directly formed on and interfacing with the TiO2 could sensitively gating the poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel, allowing unique optoelectronic detection of serum ALP level with a linear range from 0.005 to 15 U L-1 and a detection limit corresponding to 0.0012 U L-1 (S/N = 3). This study offers not only an optoelectronic method for detection of serum ALP level, but also a perspective for unique OPECT gating and application. Moreover, the general catalytic abilities of enzymes to produce functional species and their rich interactions with various gate substrates further provide great space for futuristic OPECT detection in enzyme-associated diseases.

OBJECTIVE: A simple pH and redox dual stimuli-responsive diketopyrrolopyrrole (DPP)-Cu2+ complexes gated mesoporous silica nanoparticles (MSN) were prepared for precise drug delivery and controlled drug release.
METHODS: MSN was prepared by sol-gel method and then laminated. Carboxylic acid (CA)-Pyrrolo[3,4-c] pyrrole-1,4-dione, 2,5-dihydro-3,6-di-2-pyridinyl (PyDPP) was grafted onto the surface of amino-functionalized MSN (MSN-NH2) through a simple amide reaction and then complexed with Cu2+ to form gated molecules after doxorubicin (DOX) loading.
RESULTS: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Low-angle X-ray diffraction (XRD) showed that MSN with uniform particle size (100 nm) and porous structure was successfully prepared. The prepared MSN, MSN- NH2, and MSN-DPP were fully characterized by Zeta potential, Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption- desorption. High DOX-loading capacity (18.22%) and encapsulation efficiency (89.16%) were achieved by optimizing the mass ratio of MSN to DOX. Release studies showed that the gated molecules of our designed DPP-Cu2+ complexes had a good blocking effect under physiological conditions (the cumulative release rate of drugs within 24 hours was only 4.18%) and responded well to the pH and redox glutathione (GSH) dual stimuli. In vitro cytotoxicity assay showed that MSN-DPP-Cu2+ had good biocompatibility in both Hep G2 cells and L02 cells (the relative cell viability of both cells within 48 hours was above 97%), and the MSN-DPP-Cu2+@DOX could be triggered for efficient drug release in Hep G2 cells.
CONCLUSIONS: The MSN-DPP-Cu2+ described in this research may be a good delivery system for the controlled release of antitumor drugs and can provide a potential possibility for clinical application in the future.

Eukaryotic aquaporins share the characteristic of functional multiplicity in transporting distinct substrates and regulating various processes, but the underlying molecular basis for this is largely unknown. Here, we report that the wheat (Triticum aestivum) aquaporin TaPIP2;10 undergoes phosphorylation to promote photosynthesis and productivity and to confer innate immunity against pathogens and a generalist aphid pest. In response to elevated atmospheric CO2 concentrations, TaPIP2;10 is phosphorylated at the serine residue S280 and thereafter transports CO2 into wheat cells, resulting in enhanced photosynthesis and increased grain yield. In response to apoplastic H2O2 induced by pathogen or insect attacks, TaPIP2;10 is phosphorylated at S121 and this phosphorylated form transports H2O2 into the cytoplasm, where H2O2 intensifies host defenses, restricting further attacks. Wheat resistance and grain yield could be simultaneously increased by TaPIP2;10 overexpression or by expressing a TaPIP2;10 phosphomimic with aspartic acid substitutions at S121 and S280, thereby improving both crop productivity and immunity.

The stereoisomers of menthol elicit cooling sensation to various levels. Though the high-resolution three-dimensional structures of the menthol receptor, the transient receptor potential melastatin 8 (TRPM8) ion channels, have been revolved in different states, the menthol-bound state structure is not determined and how the stereoisomers of menthol interact with TRPM8 remains largely elusive. Taking advantage of the identical atom composition but distinct spatial orientation of chemical groups in menthol stereoisomers, we performed thermodynamic mutant cycle analysis (TMCA) with patch-clamp recordings to probe the interaction between these ligands and TRPM8. By comparing (-)-menthol with (+)-neoisomenthol or (+)-neomenthol, we observed that the isopropyl or hydroxyl group in menthol interacts with the S4 or S3 helix in TRPM8, respectively. These interactions were also corroborated in our molecular docking of the stereoisomers, though the predicted structural details in the interactions of these ligands with TRPM8 residues are different. Therefore, we suggest similar molecular mechanisms of TRPM8 activation by the stereoisomers of menthol, while the binding configuration of an individual stereoisomer is varied.