AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging.

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.

Ultralow Power Wearable Organic Ferroelectric Device for Optoelectronic Neuromorphic Computing.

In order to imitate brain-inspired biological information processing systems, various neuromorphic computing devices have been proposed, most of which were prepared on rigid substrates and have energy consumption levels several orders of magnitude higher than those of biological synapses (∼10 fJ per spike). Herein, a new type of wearable organic ferroelectric artificial synapse is proposed, which has two modulation modes (optical and electrical modulation). Because of the high photosensitivity of organic semiconductors and the ultrafast polarization switching of ferroelectric materials, the synaptic device has an ultrafast operation speed of 30 ns and an ultralow power consumption of 0.0675 aJ per synaptic event. Under combined photoelectric modulation, the artificial synapse realizes associative learning. The proposed artificial synapse with ultralow power consumption demonstrates good synaptic plasticity under different bending strains. This provides new avenues for the construction of ultralow power artificial intelligence system and the development of future wearable devices.

Multiple-polarization-sensitive photodetector based on a perovskite metasurface.

Most polarization-sensitive photodetectors detect either linearly polarized (LP) or circularly polarized (CP) light. Here, we experimentally demonstrate a multiple-polarization photodetector based on a hybrid organic-inorganic perovskite (HOIP) metasurface, which is sensitive to both LP and CP light simultaneously. The perovskite metasurface is composed of a HOIP antenna array on a single-crystal HOIP film. Owing to the antenna anisotropy, the absorption of linearly polarized light at the metasurface depends on the polarization angle; also, due to the mirror asymmetry of the antenna elements, the metasurface is also sensitive to different circular polarizations. Polarization-dependent photocurrent responses to both LP and CP light are detected. Our results highlight the potential of perovskite metasurfaces for integrated photoelectric applications.

Edge-Enhanced Microwell Immunoassay for Highly Sensitive Protein Detection.

Highly sensitive biosensors that can detect low concentrations of protein biomarkers at the early stages of diseases or proteins secreted from single cells are of importance for disease diagnosis and treatment assessment. This work reports a new signal amplification mechanism, that is, edge enhancement based on the vertical sidewalls of microwells for ultra-sensitive protein detection. The fluorescence emission at the edge of the microwells is highly amplified due to the microscopic axial resolution (depth of field) and demonstrates a microring effect. The enhanced fluorescence intensity from microrings is calibrated for bovine serum albumin detection, which shows a 6-fold sensitivity enhancement and a lower limit of detection at the microwell edge, compared to those obtained on a flat surface. The microwell chip is used to separate single cells, and the wall of each microwell is used to detect interferon-γ secretion from T cells stimulated with a peptide and whole cancer cells. Given its edge-enhancement ability, the microwell technique can be a highly sensitive biosensing platform for disease diagnosis at an early stage and for assessing potential treatments at the single-cell level.

Asymmetric valley polarization and photoluminescence in MoS2/MoO3 heterostructure.

We investigate circularly polarized photoluminescence (PL) in the MoS2/MoO3 heterostructure, which was fabricated by transferring MoS2 monolayer to cover the MoO3 few layers on the SiO2/Si substrate. It is shown that the PL with the same helicity as the excitation light is dominant due to the inherent chiral optical selectivity, which allows exciting one of the valleys in MoS2 monolayer. The degree of polarization (DP), which characterizes the intensity difference of two chiral components of PL, is unequal for the right-handed and left-handed circularly polarized excitations in the MoS2/MoO3 heterostructure. This effect is different from the one in pristine MoS2. Our Raman spectra results together with ab initio calculations indicate the p-doped features of the MoS2 when it covers the MoO3 layers. Thus the possible explanation of the unequal DP is that the p-doping process generates a built-in voltage and therefore brings the difference of electron-hole overlaps between K and K' valleys. Namely the asymmetric valley polarization may be obtained in the MoS2/MoO3 heterostructure. Consequently, the circularly polarized PL caused by the electron-hole recombination at K and K' valleys manifests unequal DP for the right-handed and left-handed helix excitations. This asymmetric effect is further enhanced by decreasing the temperature in the MoS2/MoO3 heterostructure. Our investigation provides a unique platform for developing novel two-dimensional valleytronic devices.

High-performance ferroelectric field-effect transistors with ultra-thin indium tin oxide channels for flexible and transparent electronics.

With the development of wearable devices and hafnium-based ferroelectrics (FE), there is an increasing demand for high-performance flexible ferroelectric memories. However, developing ferroelectric memories that simultaneously exhibit good flexibility and significant performance has proven challenging. Here, we developed a high-performance flexible field-effect transistor (FeFET) device with a thermal budget of less than 400 °C by integrating Zr-doped HfO2 (HZO) and ultra-thin indium tin oxide (ITO). The proposed FeFET has a large memory window (MW) of 2.78 V, a high current on/off ratio (ION/IOFF) of over 108, and high endurance up to 2×107 cycles. In addition, the FeFETs under different bending conditions exhibit excellent neuromorphic properties. The device exhibits excellent bending reliability over 5×105 pulse cycles at a bending radius of 5 mm. The efficient integration of hafnium-based ferroelectric materials with promising ultrathin channel materials (ITO) offers unique opportunities to enable high-performance back-end-of-line (BEOL) compatible wearable FeFETs for edge intelligence applications.

Ferroelectric artificial synapse for neuromorphic computing and flexible applications.

Research of artificial synapses is increasing in popularity with the development of bioelectronics and the appearance of wearable devices. Because the high-temperature treatment process of inorganic materials is not compatible with flexible substrates, organic ferroelectric materials that are easier to process have emerged as alternatives. An organic synaptic device based on P(VDF-TrFE) was prepared in this study. The device showed reliable P/E endurance over 104 cycles and a data storage retention capability at 80 °C over 104 s. Simultaneously, it possessed excellent synaptic functions, including short-term/ long-term synaptic plasticity and spike-timing-dependent plasticity. In addition, the ferroelectric performance of the device remained stable even under bending (7 mm bending radius) or after 500 bending cycles. This work shows that low-temperature processed organic ferroelectric materials can provide new ideas for the future development of wearable electronics and flexible artificial synapses.

Dual-gate manipulation of a HfZrOx-based MoS2 field-effect transistor towards enhanced neural network applications.

Artificial neural networks (ANNs) have strong learning and computing capabilities, and alleviate the problem of high power consumption of traditional von Neumann architectures, providing a solid basis for advanced image recognition, information processing, and low-power detection. Recently, a two-dimensional (2D) MoS2 field-effect transistor (FET) integrating a Zr-doped HfO2 (HZO) ferroelectric layer has shown potential for both logic and memory applications with low power consumption, which is promising for parallel processing of massive data. However, the long-term potentiation (LTP) characteristics of such devices are usually non-linear, which will affect the replacement of ANN weight values and degrade the ANN recognition rate. Here, we propose a dual-gate-controlled 2D MoS2 FET employing HZO gate stack with a crested symmetric structure to reduce power consumption. Improved nonlinearity of the LTP properties has been achieved through the electrical control of the dual gates. A recognition rate reaching 100% is obtained after 60 training epochs, and is 7.89% higher than that obtained from single-gate devices. Our proposed device structure and experimental results provide an attractive pathway towards high-efficiency data processing and image classification in the advanced artificial intelligence field.

Cancer Treatment Evolution from Traditional Methods to Stem Cells and Gene Therapy.

BACKGROUND: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine. METHODS: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects. DISCUSSION: In this study, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials, and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment. CONCLUSION: This review focuses on the current status, application prospects, and challenges of mesenchymal stem cell combined gene therapy for cancer and provides new ideas for clinical research.

Reconfigurable neuromorphic memristor network for ultralow-power smart textile electronics.

Neuromorphic computing memristors are attractive to construct low-power- consumption electronic textiles due to the intrinsic interwoven architecture and promising applications in wearable electronics. Developing reconfigurable fiber-based memristors is an efficient method to realize electronic textiles that capable of neuromorphic computing function. However, the previously reported artificial synapse and neuron need different materials and configurations, making it difficult to realize multiple functions in a single device. Herein, a textile memristor network of Ag/MoS2/HfAlOx/carbon nanotube with reconfigurable characteristics was reported, which can achieve both nonvolatile synaptic plasticity and volatile neuron functions. In addition, a single reconfigurable memristor can realize integrate-and-fire function, exhibiting significant advantages in reducing the complexity of neuron circuits. The firing energy consumption of fiber-based memristive neuron is 1.9 fJ/spike (femtojoule-level), which is at least three orders of magnitude lower than that of the reported biological and artificial neuron (picojoule-level). The ultralow energy consumption makes it possible to create an electronic neural network that reduces the energy consumption compared to human brain. By integrating the reconfigurable synapse, neuron and heating resistor, a smart textile system is successfully constructed for warm fabric application, providing a unique functional reconfiguration pathway toward the next-generation in-memory computing textile system.

Enhanced Turn-On Fluorescence Detection of Aqueous Lead Ions with Size-Shrinkable Hydrogels.

Highly sensitive detection of lead ions in water is of importance. This paper reports a new method to enhance the sensitivity of fluorescence detection of aqueous lead ions by exploiting the large volume reduction of hydrogels upon dehydration. Rhodamine-derived prefluorescent probes with high selectivity to lead ions are grafted on a carboxylated agarose hydrogel. Upon binding low-concentration lead ions, fluorescence emission is turned on. The dehydration of the hydrogel leads to a size reduction of over 40 times and an enhancement of fluorescence of 10 times at a lead-ion concentration of 10-7 M, allowing fluorescence detection with naked eyes. Given its low cost, easy operation, and high sensitivity, the volume reduction hydrogel can be used to detect lead ions in drinking water.

[High glucose promotes the expression of DNA methyltransferase 3B (DNMT3B) in cultured mouse renal tubular epithelial cells and promotes the secretion of fibrosis associated proteins by activating the Wnt/ß-catenin signaling pathway].

Objective To observe the effects of DNA methyltransferase 3B (DNMT3B) on the expression of secreted frizzled-related protein 1 (SFRP1) and regulation of Wnt/ß-catenin signaling pathway in renal tubular epithelial cells (RTECs) of mice under high glucose conditions. Methods in vitro cultured mouse RTECs were divided into normal glucose (NG) group and high glucose (HG) group. After DNMT3B short-hairclip RNA (sh-DNMT3B) and DNMT3B over-expression (DNMT3B-OE) plasmids were transfected separately into RTECs, mRNA expression of DNMT3B, SFRP1, collagen IV (Col4) and fibronectin (FN) were detected by reverse-transcription PCR. Protein expression of DNMT3B, SFRP1, glycogen synthase kinase 3ß (GSK3ß), phosphorylated glycogen synthase kinase 3ß (p-GSK3ß), ß-catenin, Col4 and FN were detected by Western blotting. The localization of DNMT3B and SFRP1 in RTECs was observed by immunofluorescence cytochemistry combined with confocal microscopy. Results Compared with the NG group, the protein expression of DNMT3B, ß-catenin, p-GSK3ß, Col4 and FN increased in the HG group, while SFRP1 protein expression was reduced in the HG group. Compared with the sh-vector group, SFRP1 mRNA and protein expression increased in the sh-DNMT3B group, while the expression of ß-catenin, p-GSK3ß and Col4 proteins decreased. FN mRNA and protein expression dropped in the sh-DNMT3B group, however, the expression of ß-catenin mRNA did not change significantly. Visually, DNMT3B over-expression reversed the above changes. Both DNMT3B and SFRP1 were expressed in the nucleus and cytoplasm of RTECs, and DNMT3B was aggregated in the nuclei of the cells in the HG group and the co-localization between DNMT3B and SFRP1 was also promoted in the HG group. Conclusion The expression of DNMT3B increases and the expression of SFRP1 decreases when the mouse RTECs were stimulated by HG. This subsequently leads to the activation of the Wnt/ß-catenin signaling pathway and promotes the formation of extracellular matrix.

Flexible organic field-effect transistor arrays for wearable neuromorphic device applications.

With the advent of wearable microelectronic devices in the interdisciplinary bio-electronics research field, synaptic devices with capability of neuromorphic computing are attracting more and more attention as the building blocks for the next generation computing structure. Conventional flash-like synaptic transistors are built on rigid solid-state substrates, and the inorganic materials and the high-temperature processing steps have severely limited their applications in various flexible electronic devices and systems. Here, flexible organic flash-like synaptic devices have been fabricated on a flexible substrate with the organic C8-BTBT as the conducting channel. The device exhibits a memory window greater than 20 V and excellent synaptic functions including short/long-term synaptic plasticity and spike-timing-dependent plasticity. In addition, even under the bending condition (7 mm bending radius), the transistor can still stably achieve a variety of synaptic functions. This work shows that low-temperature processing technology with the integration of organic materials can pave a promising pathway for the realization of flexible synaptic systems and the future development of wearable electronic devices.

Single identical cell toxicity assay on coordinately ordered patterns.

Toxicity assay is crucial in identifying biological mechanisms, detecting disease and screening therapeutics. Single cell toxicity assay reveals heterogeneous responses of each cell without ensemble average, but still cannot indicate responses of the same individual cells to multiple treatments. This article reports an identical cell assay that can be used at high throughput to locate each cell and track its responses to multiple treatments (chemicals and radiation), thus greatly facilitates toxicity based drug screening and testing. Each cell is located through its coordinators pre-engraved on a patterned substrate with soft lithography. Cell responses to X-ray radiation, chemical reagents or a combination of both are obtained by probing reactive oxygen species (ROS) signals and quantified by fluorescent intensity in MATLAB. The method can provide toxicities of over thousands of identical cells with superior statistics power to allow deep analysis of toxicity data.

The preparation and morphology control of heparin-based pH sensitive polyion complexes and their application as drug carriers.

Heparin as negative polysaccharide is a universal building block to form polyion complex with different cationic counterparts. In this paper, three different cations, including chitosan, benzyldodecyldimethyl ammonium bromide and doxorubicin hydrochloride, were used to prepare heparin-based polyion complexes (HPICs). Their morphologies could be tuned by heparin content in HPIC, and they also showed pH-sensitive decomposition. Doxorubicin was further encapsulated into micelle and vesicle carrier made from heparin-benzyldodecyl dimethyl ammonium bromide PIC, whereas heparin-doxorubicin PIC could be directly used as drug carrier. In vitro drug release proved the drug carriers exhibit obvious pH sensitive release behaviour. Cytotoxicity indicated the drug carrier possessed significant cytotoxicity to tumor cells. The cell uptake observed by CLSM showed the carrier was able to deliver antitumor drug into tumor cell's nucleus. Consequently, these results showed the promising potential of HPIC in drug carrier application.

Whole slide imaging of circulating tumor cells captured on a capillary microchannel device.

Liquid biopsy with circulating tumor cells (CTCs) can aid in cancer detection at early stages and determine whether a certain treatment is effective or not. However, existing CTC techniques focus on one or two aspects of CTC management including sampling, enrichment, enumeration, and treatment selection. This paper reports an integrated capillary microchannel device that allows efficient capturing of CTCs with a wide microchannel, rapid enumeration of captured CTCs with whole slide cell imaging, and in situ drug testing with captured CTCs. Blood is drawn into the microchannel whose height is appropriate to the diameter of cancer cells, while its width is a thousand times larger than the diameter of cancer cells. The inner bottom surface of the microchannel is modified with long chain polymers that have cell adhesive ends to efficiently capture CTCs from blood. With this design, cells including CTCs are forced to move through the polymer coated microchannel, and the chance of cell adhesive ends interacting with specific antigens overexpressed on surfaces of cancer cells is significantly enhanced without a channel blockage issue. Captured CTCs are enumerated with a whole slide imaging platform via dual LED autofocusing technology then exposed to anti-cancer drugs, followed by live/dead assay and fluorescence imaging. Given its straightforward, easy and powerless operation, this device with whole slide imaging will be useful for cancer diagnosis, prognosis and point-of-care treatments.

Surface charge controlled nucleoli selective staining with nanoscale carbon dots.

Organelle selective imaging can reveal structural and functional characters of cells undergoing external stimuli, and is considered critical in revealing biological fundamentals, designing targeted delivery system, and screening potential drugs and therapeutics. This paper describes the nucleoli targeting ability of nanoscale carbon dots (including nanodiamond) that are hydrothermally made with controlled surface charges. The surface charges of carbon dots are controlled in the range of -17.9 to -2.84 mV by changing the molar ratio of two precursors, citric acid (CA) and ethylenediamine (EDA). All carbon dots samples show strong fluorescence under wide excitation wavelength, and samples with both negative and positve charges show strong fluorescent contrast from stained nucleoli. The nucleoli selective imaging of live cell has been confirmed with Hoechst staining and nucleoli specific staining (SYTO RNA-select green), and is explained as surface charge heterogeneity on carbon dots. Carbon dots with both negative and positive charges have better ability to penetrate cell and nucleus membranes, and the charge heterogeneity helps carbon dots to bind preferentially to nucleoli, where the electrostatic environment is favored.

Nanocellulose templated growth of ultra-small bismuth nanoparticles for enhanced radiation therapy.

An unmet need in nanomedicine is to prepare biocompatible and renal clearable nanoparticles by controlling the diameter, composition and surface properties of the nanoparticles. This paper reports cellulose nanofiber templated synthesis of ultra-small bismuth nanoparticles, and their uses in enhanced X-ray radiation therapy. The interstitial spaces between adjacent fibers are the adsorption sites of bismuth ions and also stabilize nanoparticles generated by chemical reduction. The sizes of nanoparticles are tailored in the 2-10 nm range using cellulose nanofibers with various amounts of carboxyl groups. In vitro cytotoxicity, reactive oxygen species (ROS) and in vivo animal tests with tumor-bearing mice are studied in order to enhance X-ray radiation therapy using cellulose nanofiber-templated bismuth nanoparticles. Bismuth nanoparticles show strong X-ray attenuation ability, concentration-dependent cytotoxicity and high level production of ROS upon X-ray exposure, which is consistent with enhanced cellular damage and retarded growth of tumors in animals.

Enhanced Radiation Shielding with Conformal Light-Weight Nanoparticle-Polymer Composite.

This article reports a new property enabled by nanoparticles, where bismuth nanoparticles added in a polymer matrix can block X-ray radiation several times more efficient than microparticles at the same mass ratio. Bismuth nanoparticles are made with cellulose nanofibers and dispersed evenly into a polymer. A four time reduction in the mass of bismuth material is identified at 2% mass ratio when nanoparticles (5 nm in diameter) are used in composite to shield a given flux and energy of radiation, in relative to those of microparticles (5 µm diameter). The enhancement in radiation shielding is primarily attributed to close packing of nanoparticles normal to incoming X-ray direction, which is enabled by strong affinity of nanoparticles to interstitial space of cellulose nanofibers and even distribution of nanoparticles inside polymer. Given its low cost, light weight, and structure conformability, bismuth nanoparticle-polymer composite will find its use in a wide range of fields related to personal radiation protection.

Probing the effect of tip pressure on fungal growth: Application to Aspergillus nidulans.

The study of fungal cells is of great interest due to their importance as pathogens and as fermenting fungi and for their appropriateness as model organisms. The differential pressure between the hyphal cytoplasm and the bordering medium is essential for the growth process, because the pressure is correlated with the growth rate. Notably, during the invasion of tissues, the external pressure at the tip of the hypha may be different from the pressure in the surrounding medium. We report the use of a method, based on the micropipette-aspiration technique, to study the influence of this external pressure at the hyphal tip. Moreover, this technique makes it possible to study hyphal growth mechanics in the case of very thin hyphae, not accessible to turgor pressure probes. We found a correlation between the local pressure at the tip and the growth rate for the species Arpergillus nidulans. Importantly, the proposed method allows one to measure the pressure at the tip required to arrest the hyphal growth. Determining that pressure could be useful to develop new medical treatments for fungal infections. Finally, we provide a mechanical model for these experiments, taking into account the cytoplasm flow and the wall deformation.