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Abstract A flexible optoelectronic neural transistor (OENT) that consists of a one‐step spin‐coated tri‐blend film composed of 2,7‐dioctyl[1]benzothieno[3,2‐b][1]benzothiophene (C8‐BTBT), poly(3‐hexylthiophene‐2,5‐diyl) (P3HT), and poly(methyl methacrylate) (PMMA) is demonstrated. The C8‐BTBT and P3HT phases in the film partially segregate into distinct domains, which combine to provide broadband spectrum sensing, and instant electrical‐processing capabilities dominated by C8‐BTBT. The OENT is sensitive to solar radiation from the near‐ultraviolet (NUV) and to visible (Vis) radiation from blue to red. When exposed to NUV radiation, the OENT responds sensitively and retains the memory of the exposure for over 103 s. The OENT provides a warning of excessive chronic exposure to harmful NUV. These properties allow high‐pass filtering with different cut‐off frequencies fc that can restrict the reception of blue, green, or red. These switchable fc enables sensitive image reconstruction and multitarget monitoring. The device combined with a chitosan gel achieves strictly defined short‐range plasticity of

Amycolatopsis is an important source of diverse valuable bioactive natural products. The CRISPR/Cas-mediated gene editing tool has been established in some Amycolatopsis species and has accomplished the deletion of single gene or two genes. The goal of this study was to develop a high-efficient CRISPR/Cas9-mediated genome editing system in vancomycin-producing strain A. keratiniphila HCCB10007 and enhance the production of vancomycin by deleting the large fragments of ECO-0501 BGC. By adopting the promoters of gapdhp and ermE*p which drove the expressions of scocas9 and sgRNA, respectively, the all-in-one editing plasmid by homology-directed repair (HDR) precisely deleted the single gene gtfD and inserted the gene eGFP with the efficiency of 100%. Furthermore, The CRISPR/Cas9-mediated editing system successfully deleted the large fragments of cds13-17 (7.7 kb), cds23 (12.7 kb) and cds22-23 (21.2 kb) in ECO-0501 biosynthetic gene cluster (BGC) with high efficiencies of 81%–97% by selecting the sgRNAs with a suitable PAM sequence. Finally, a larger fragment of cds4-27 (87.5 kb) in ECO-0501 BGC was deleted by a dual-sgRNA strategy. The deletion of the ECO-0501 BGCs revealed a noticeable improvement of vancomycin production, and the mutants, which were deleted the ECO-0501 BGCs of cds13-17, cds22-23 and cds4-27, all achieved a 30%–40% increase in vancomycin yield. Therefore, the successful construction of the CRISPR/Cas9-mediated genome editing system and its application in large fragment deletion in A. keratiniphila HCCB10007 might provide a powerful tool for other Amycolatopsis species.

Aims To examine differences between the eyes in choriocapillaris perfusion and choroidal thickness in children with myopic anisometropia. Methods In this observational and prospective study, 46 children with myopic anisometropia were enrolled. Choriocapillaris perfusion parameters, including the percentage of flow voids, the total number of flow voids and the average flow void area were obtained by optical coherence tomography angiography (OCTA). The OCTA image was divided into a 1 mm-diameter central circle (C1) and a 2.5 mm-diameter annulus (without the inner central 1 mm circle, C1-2.5). Both C1 and C1-2.5 are centred on the foveola. The C1-2.5 was divided into nasal (N1-2.5), temporal (T1-2.5), inferior (I1-2.5) and superior (S1-2.5) areas. Differences in these parameters in different regions between eyes were analysed. Results There were no significant differences in the percentage of flow voids and the average flow void area between the fellow eyes. The total number of signal voids was significantly higher in the less myopic eyes in C1-2.5 (p=0.032), S1-2.5 (p=0.008) and N1-2.5 (p=0.019). Changes in spherical equivalent refraction and axial length were both correlated with the changes in the total number of flow voids in N1-2.5 (R=-0.431, p=0.03; R=-0.297, p=0.047). Conclusions The choroid in the macular region becomes thinner and the total number of flow voids in the nasal macular region decreased with the amplitude of myopia. This suggests that a decrease in total number of flow voids may indicate an early change in myopia. [ABSTRACT FROM AUTHOR]

BACKGROUND: The incidence of kidney tumors is progressively increasing each year. The precision of segmentation for kidney tumors is crucial for diagnosis and treatment. OBJECTIVE: To enhance accuracy and reduce manual involvement, propose a deep learning-based method for the automatic segmentation of kidneys and kidney tumors in CT images. METHODS: The proposed method comprises two parts: object detection and segmentation. We first use a model to detect the position of the kidney, then narrow the segmentation range, and finally use an attentional recurrent residual convolutional network for segmentation. RESULTS: Our model achieved a kidney dice score of 0.951 and a tumor dice score of 0.895 on the KiTS19 dataset. Experimental results show that our model significantly improves the accuracy of kidney and kidney tumor segmentation and outperforms other advanced methods. CONCLUSION: The proposed method provides an efficient and automatic solution for accurately segmenting kidneys and renal tumors on CT images. Additionally, this study can assist radiologists in assessing patients' conditions and making informed treatment decisions. [ABSTRACT FROM AUTHOR]

Abstract The ability to emulate multiplexed neurochemical transmission is an important step toward mimicking complex brain activities. Glutamate and dopamine are neurotransmitters that regulate thinking and impulse signals independently or synergistically. However, emulation of such simultaneous neurotransmission is still challenging. Here we report design and fabrication of synaptic transistor that emulates multiplexed neurochemical transmission of glutamate and dopamine. The device can perform glutamate-induced long-term potentiation, dopamine-induced short-term potentiation, or co-release-induced depression under particular stimulus patterns. More importantly, a balanced ternary system that uses our ambipolar synaptic device backtrack input ‘true’, ‘false’ and ‘unknown’ logic signals; this process is more similar to the information processing in human brains than a traditional binary neural network. This work provides new insight for neuromorphic systems to establish new principles to reproduce the complexity of a mammalian central nervous system from simple basic units.

Constructing artificial sensorimotor systems for robotic applications calls for development of synaptic connections for complicated information processing. Wei et al. propose a graphdiyne-based artificial synapse capable of parallel processing signals and utilize it in an artificial mechanoreceptor system.

Abstract Background Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes. Results Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA, CXCL2, and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1, AC037198.2, AL929472.2, and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways. Conclusion Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients.

Abstract The first flexible organic‐heterojunction neuromorphic transistor (OHNT) that senses broadband light, including near‐ultraviolet (NUV), visible (vis), and near‐infrared (NIR), and processes multiplexed‐neurotransmission signals is demonstrated. For UV perception, electrical energy consumption down to 536 aJ per synaptic event is demonstrated, at least one order of magnitude lower than current UV‐sensitive synaptic devices. For NIR‐ and vis‐perception, switchable plasticity by alternating light sources is yielded for recognition and memory. The device emulates multiplexed neurochemical transition of different neurotransmitters such as dopamine and noradrenaline to form short‐term and long‐term responses. These facilitate the first realization of human‐integrated motion state monitoring and processing using a synaptic hardware, which is then used for real‐time heart monitoring of human movement. Motion state analysis with the 96% accuracy is then achieved by artificial neural network. This work provides important support to future biomedical electronics and neural prostheses.

Alzheimer's disease (AD) is a neurodegenerative disease and threatens the health of the aged population worldwide. In the present study, we investigated cognitive improvement by aloe emodin in aluminum‐induced AD rats. We orally administered aluminum chloride (150 mg/kg) to Sprague–Dawley rats for 8 weeks to induce AD. In the 5th to the 8th week, the rats were injected intraperitoneally with AE (5, 10, and 15 mg/kg). Behavioral, histopathological, and biochemical assessments were performed. The results showed that AE alleviated cognitive impairment in aluminum‐induced AD rats and inhibited aluminum‐induced hippocampal neuronal damage. Furthermore, aloe emodin relieved the aluminum burden in the brain of aluminum‐induced AD rats, attenuated the aluminum‐induced increase in Aβ42 level and acetylcholinesterase activity, and reduced the levels of tumor necrosis factor‐α, interleukin‐6, interleukin‐1α, and interleukin‐1β. These effects suggest that the mechanism by which AE alleviates AD‐related cognitive impairment is by removal of excess aluminum, decreasing Aβ42 deposition, regulating the cholinergic system, and reducing neuroinflammation. [ABSTRACT FROM AUTHOR]

Integrated Raman microlasers, particularly discrete multi‐color lasers which are crucial for extending the emission wavelength range of chip‐scale laser sources to much shorter wavelengths, are highly in demand for various spectroscopy, microscopy analysis, and biological detection applications. However, integrated multi‐color Raman microlasers have yet to be demonstrated because of the requirement of high‐Q microresonators possessing large χ(2) nonlinearity, strong Raman phonon branches, and the challenge in the cavity‐enhanced multi‐photon hyper‐Raman scattering parametric process. In this work, integrated multi‐color Raman lasers have been demonstrated for the first time at weak pump levels, via the excitation of high‐Q (> 6 × 106) phase‐matched modes in single thin‐film lithium niobate (TFLN) microresonators by dispersion engineering. Raman lasing is observed at 1712 nm for a 1547‐nm pump threshold power of only 620 µW, representing the state of the art in the TFLN platform. Furthermore, multi‐color Raman lasers are realized at discrete wavelengths of 1712, 813, 533, and 406 nm with pump levels as low as 1.60 mW, which is more than two orders of magnitude lower than the current records (i.e., 200 mW) in bulk resonators, allowed by the fulfillment of the requisite conditions consisting of broadband natural phase match, multiple‐resonance, and high‐Q factors. [ABSTRACT FROM AUTHOR]

Background: Previous studies have highlighted the association between schizophrenia (SCZ) and chronic obstructive pulmonary disease (COPD), yet the causal relationship remains unestablished. Methods: Under the genome-wide significance threshold (P<5x10-8), data from individuals of European (EUR) and East Asian (EAS) ancestries with SCZ were selected for analysis. Univariable Mendelian randomization (MR) explored the causal relationship between SCZ and COPD. Linkage disequilibrium score (LDSC) regression was used to calculate genetic correlation, while multivariable and mediation MR further investigated the roles of six confounding factors and their mediating effects. The primary method utilized was inverse-variance weighted (IVW), complemented by a series of sensitivity analyses and false discovery rate (FDR) correction. Results: LDSC analysis revealed a significant genetic correlation between SCZ and COPD within EUR ancestry (rg = 0.141, P = 6.16x10-7), with no such correlation found in EAS ancestry. IVW indicated a significant causal relationship between SCZ and COPD in EUR ancestry (OR = 1.042, 95% CI 1.013-1.071, P = 0.003, PFDR = 0.015). Additionally, replication datasets provide evidence of consistent causal associations(P < 0.05 & PFDR < 0.05). Multivariable and mediation MR analyses identified body mass index (BMI)(Mediation effect: 50.57%, P = 0.02), age of smoking initiation (Mediation effect: 27.42%, P = 0.02), and major depressive disorder (MDD) (Mediation effect: 60.45%, P = 6.98x10-5) as partial mediators of this causal relationship. No causal associations were observed in EAS (OR = 0.971, 95% CI 0.875-1.073, P = 0.57; PFDR = 0.761) ancestry. No causal associations were found in the reverse analysis across the four ancestries (P > 0.05 & PFDR > 0.05). Conclusions: This study confirmed a causal relationship between SCZ and the risk of COPD in EUR ancestry, with BMI, smoking, and MDD serving as key mediators. Future research on a larger scale is necessary to validate the generalizability of these findings across other ancestries. [ABSTRACT FROM AUTHOR]

Flexible electronics has attracted tremendous attention in recent years. The essential requirements for flexible electronics include excellent electrical properties, flexibility and stretchability. By introducing special structures or using flexible materials, electronic devices can be given excellent flexibility and stretchability. In this paper we review the realization of flexible electronics from the perspective of structural design strategies and materials; then, healthcare application of flexible electronic systems was introduced. Finally, a brief summary and outlook are presented.

Enalaprilat is the active metabolite of enalapril, a widely used antihypertension drug. The human organic anion transporter 3 (OAT3), which is highly expressed in the kidney, plays a critical role in the renal clearance of many drugs. While urinary excretion is the primary elimination route of enalaprilat, direct involvement of OAT3 has not been reported so far. In the present study, OAT3-mediated uptake of enalaprilat was first characterized, and the inhibition of OAT3 transport activity was then examined for a number of flavonoid and drug molecules with diverse structures. A varying degree of inhibition potency was demonstrated for flavonoids, with IC50 values ranging from 0.03 to 22.6 µM against OAT3 transport activity. In addition, commonly used drugs such as urate transporter 1 (URAT1) inhibitors also displayed potent inhibition on OAT3-mediated enalaprilat uptake. Pharmacophore and three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses revealed the presence of a polar center and a hydrophobic region involved in OAT3-inhibitor binding. For the polar center, hydroxyl groups present in flavonoids could act as either hydrogen bond donors or acceptors and the number and position of hydroxyl groups were critical drivers for inhibition potency, while carboxyl groups present in some drugs could form ionic bridges with OAT3. The predicted inhibition potencies by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were correlated well with experimental IC50 values. Taken together, the present study identified OAT3-mediated uptake of enalaprilat as an important mechanism for its renal clearance, which may be liable for drug-drug and herb-drug interactions. The established computational models revealed unique structural features for OAT3 inhibitors and could be used for structure-activity relationship (SAR) analysis of OAT3 inhibition. The clinical relevance of the inhibition of OAT3-mediated enalaprilat uptake warrants further investigation, particularly in populations where herbal remedies and drugs are used concomitantly.

A multi-node all-optical interconnect network-routing architecture scheme and implementation technology are designed to improve high-speed and large-capacity data transmission in data centers. In the design of the optical interconnect routing electro-optic printed circuit board (EOPCB), the signal generated by the FPGA is directly modulated by the VCSEL arrays, and through the coupler into the parallel optical waveguide. The transmission link and optical switch are operated in optical domain. The designed optical waveguide comprises 12 waveguide arrays with the space of 250 μm. The all-optical interconnection routing system, which is based on the EOPCB high-speed chip multi-node waveguide, is designed, and a 4 × 4 EOPCB is fabricated. The performance of the waveguide and the entire optical interconnection network is tested. Based on 10 Gb/s VCSEL arrays, the optical interconnect network system can reach a bandwidth of 640 GHz for 4 × 4 networks. The best bit error rate for the switching system can reach 9.0 × 10-12 with no transmission error.

In biological synapses, short‐term plasticity is important for computation and signal transmission, whereas long‐term plasticity is essential for memory formation. Comparably, designing a strategy that can easily tune the synaptic plasticity of artificial synapses can benefit constructing an artificial neural system, where synapses with different short‐term plasticity (STP) and long‐term plasticity (LTP) are required. Herein, a strategy is designed that can easily tune the plasticity of crystallized conjugated polymer nanowire‐based synaptic transistors (STs) by low‐temperature solvent engineering. Essential synaptic functions are achieved, such as excitatory postsynaptic current (EPSC), paired‐pulse facilitation (PPF), spike‐frequency‐dependent plasticity (SFDP), spike‐duration‐dependent plasticity (SDDP) and spike‐number‐dependent plasticity (SNDP), and potentiation/depression. The balance between crystallinity and roughness is successfully adjusted by altering solvent compositions, and plasticity of the synaptic device is easily tuned between short term and long term. The evident transition from STP to LTP, good linearity and symmetry of potentiation and depression, and the broad dynamic working range of synaptic weight are achieved. This provides a facile way to tune synaptic plasticity at low temperatures and is applicable to future organic and flexible artificial nervous systems.

Electronic skin, a class of wearable electronic sensors that mimic the functionalities of human skin, has made remarkable success in applications including health monitoring, human-machine interaction and electronic-biological interfaces. While electronic skin continues to achieve higher sensitivity and faster response, its ultimate performance is fundamentally limited by the nature of low-frequency AC currents. Herein, highly sensitive skin-like wearable optical sensors are demonstrated by embedding glass micro/nanofibers (MNFs) in thin layers of polydimethylsiloxane (PDMS). Enabled by the transition from guided modes into radiation modes of the waveguiding MNFs upon external stimuli, the skin-like optical sensors show ultrahigh sensitivity (1870 kPa-1), low detection limit (7 mPa) and fast response (10 μs) for pressure sensing, significantly exceeding the performance metrics of state-of-the-art electronic skins. Electromagnetic interference (EMI)-free detection of high-frequency vibrations, wrist pulse and human voice are realized. Moreover, a five-sensor optical data glove and a 2×2-MNF tactile sensor are demonstrated. These initial results pave the way toward a new category of optical devices ranging from ultrasensitive wearable sensors to optical skins.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions. [ABSTRACT FROM AUTHOR]

The ionic environment of body fluids influences nervous functions for maintaining homeostasis in organisms and ensures normal perceptual abilities and reflex activities. Neural reflex activities, such as limb movements, are closely associated with potassium ions (K+). In this study, we developed artificial synaptic devices based on ion concentration-adjustable gels for emulating various synaptic plasticities under different K+ concentrations in body fluids. In addition to performing essential synaptic functions, potential applications in information processing and associative learning using short- and long-term plasticity realized using ion concentration-adjustable gels are presented. Artificial synaptic devices can be used for constructing an artificial neural pathway that controls artificial muscle reflex activities and can be used for image pattern recognition. All tests show a strong relationship with ion homeostasis. These devices could be applied to neuromorphic robots and human-machine interfaces. [ABSTRACT FROM AUTHOR]