An Organic Optoelectronic Synapse with Multilevel Memory Enabled by Gate Modulation.

Artificial synaptic devices are emerging as contenders for next-generation computing systems due to their combined advantages of self-adaptive learning mechanisms, high parallel computation capabilities, adjustable memory level, and energy efficiency. Optoelectronic devices are particularly notable for their responsiveness to both voltage inputs and light exposure, making them attractive for dynamic modulation. However, engineering devices with reconfigurable synaptic plasticity and multilevel memory within a singular configuration present a fundamental challenge. Here, we have established an organic transistor-based synaptic device that exhibits both volatile and nonvolatile memory characteristics, modulated through gate voltage together with light stimuli. Our device demonstrates a range of synaptic behaviors, including both short/long-term plasticity (STP and LTP) as well as STP-LTP transitions. Further, as an encoding unit, it delivers exceptional read current levels, achieving a program/erase current ratio exceeding 105, with excellent repeatability. Additionally, a prototype 4 × 4 matrix demonstrates potential in practical neuromorphic systems, showing capabilities in the perception, processing, and memory retention of image inputs.

Bioorthogonal photocatalytic proximity labeling in primary living samples.

In situ profiling of subcellular proteomics in primary living systems, such as native tissues or clinic samples, is crucial for understanding life processes and diseases, yet challenging due to methodological obstacles. Here we report CAT-S, a bioorthogonal photocatalytic chemistry-enabled proximity labeling method, that expands proximity labeling to a wide range of primary living samples for in situ profiling of mitochondrial proteomes. Powered by our thioQM labeling warhead development and targeted bioorthogonal photocatalytic chemistry, CAT-S enables the labeling of mitochondrial proteins in living cells with high efficiency and specificity. We apply CAT-S to diverse cell cultures, dissociated mouse tissues as well as primary T cells from human blood, portraying the native-state mitochondrial proteomic characteristics, and unveiled hidden mitochondrial proteins (PTPN1, SLC35A4 uORF, and TRABD). Furthermore, CAT-S allows quantification of proteomic perturbations on dysfunctional tissues, exampled by diabetic mouse kidneys, revealing the alterations of lipid metabolism that may drive disease progression. Given the advantages of non-genetic operation, generality, and spatiotemporal resolution, CAT-S may open exciting avenues for subcellular proteomic investigations of primary samples that are otherwise inaccessible.

Buoyancy of underground structures and pore water pressure conduction law in silty clay strata.

Based on the effective stress principle, indoor model tests were conducted in this study to calculate the buoyancy of an underground structure and determine the law of pore water pressure conduction in silty clay strata. A comprehensive underground structure-water-soil interaction test system was established with four-in-one features: Elimination of lateral friction, controllable water head, circulating water supply and drainage, and simulation of groundwater flow. Four- and seven-gradient buoyancy continuous monitoring tests were completed using fine sand and silty clay, respectively, to verify the reliability and accuracy of the test system. The hydrostatic pressure and seepage-hydrostatic process of the silty clay strata were simulated separately to investigate the buoyancy of the underground structure of the strata, the buoyancy reduction coefficient, and the pore water pressure conduction law. The results show the reliability and accuracy of the comprehensive test system for underground structure-water-soil interaction. The concept of "buoyancy starting intercept" is proposed based on this system, where the underground water level value should be the head of water supply minus the "buoyancy starting intercept" when calculating buoyancy in weak permeable layers. Under hydrostatic action, the groundwater is phreatic, deeper burial depths show greater magnitude of this discount. When the groundwater is confined, the water head reduction coefficient increases with increase in the burial depth or hydraulic gradient. Buoyancy calculations of an underground structure within the range of confined water should not be reduced in this case. Whether in a seepage or hydrostatic state, the pore water pressure in the silty clay layer is below the theoretical value. The results of this work may provide a theoretical basis for further analysis of the pore water pressure conduction law and buoyancy reduction mechanism of clay soils. We also may provide a theoretical reference for the development of innovative underground structure-water-soil interaction comprehensive test systems.

Near-Infrared Organic Photodetectors toward Skin-Integrated Photoplethysmography-Electrocardiography Multimodal Sensing System.

In the fast-evolving landscape of decentralized and personalized healthcare, the need for multimodal biosensing systems that integrate seamlessly with the human body is growing rapidly. This presents a significant challenge in devising ultraflexible configurations that can accommodate multiple sensors and designing high-performance sensing components that remain stable over long periods. To overcome these challenges, ultraflexible organic photodetectors (OPDs) that exhibit exceptional performance under near-infrared illumination while maintaining long-term stability are developed. These ultraflexible OPDs demonstrate a photoresponsivity of 0.53 A W-1 under 940 nm, shot-noise-limited specific detectivity of 3.4 × 1013 Jones, and cut-off response frequency beyond 1 MHz at -3 dB. As a result, the flexible photoplethysmography sensor boasts a high signal-to-noise ratio and stable peak-to-peak amplitude under hypoxic and hypoperfusion conditions, outperforming commercial finger pulse oximeters. This ensures precise extraction of blood oxygen saturation in dynamic working conditions. Ultraflexible OPDs are further integrated with conductive polymer electrodes on an ultrathin hydrogel substrate, allowing for direct interface with soft and dynamic skin. This skin-integrated sensing platform provides accurate measurement of photoelectric and biopotential signals in a time-synchronized manner, reproducing the functionality of conventional technologies without their inherent limitations.

Construction of universal equations for knot attributes of three coniferous species.

We constructed base model, dummy variable model, and mixture model with three variables including knot diameter, loose knot length, and sound knot length with three typical coniferous species, Pinus koraiensis, Larix olgensis, and Pinus sylvestris var. mongolica, from the Linkou Forestry Bureau and Mengjiagang forest farm in Heilongjiang Province in 2020. We analyzed the differences in knot properties among different tree species and simplified the modeling work. Firstly, we collected relevant knot property data through the sectioning method based on relevant literature, transformation of the model form and substitution of related variables to conduct a base model. We transformed the species into dummy variables as qualitative factors, and introduced the dummy variable model of the relevant attributes into the base model. We introduced the random effects of sample trees and sample plots when constructing the mixture model. By comparing evaluation indicators, such as Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), the mixture model with the best fitting effect was selected. We selected the optimal universal equation by comparing the fitting accuracy of the base model, dummy variable model and mixture model. The fitting accuracy of the dummy variable model and mixture model was higher than that of the basic model. The evaluation indicators (AIC and BIC) showed that the mixture model had a better fitting effect on knot properties than the dummy variable model. In the model comparison results, R2 of mixture models for sound knot length, the loose knot length, and knot diameter increased by 13.2%, 84.8% and 40.3%, respectively. The predictive accuracy of the three base models for different tree species' knot attributes was above 90%, and both the prediction accuracy of the dummy variable model and mixture model were above 94%, indicating that the constructed models could well predict knot-related properties. From the perspective of tree species, the sound knot length, knot diameter, and loose knot length was in order of P. sylvestris var. mongolica > P. koraiensis > L. olgensis. Fitted results of the dummy variable model and the mixture model were superior to the basic model, with higher accuracy.

Electric-field induced half-metallic properties in an experimentally synthesized CrSBr monolayer.

Two-dimensional (2D) half-metallic materials are highly desirable for nanoscale spintronic applications. Here, we propose a new mechanism that can achieve half-metallicity in 2D ferromagnetic (FM) materials with two-layer magnetic atoms by electric field tuning. We use a concrete example of an experimentally synthesized CrSBr monolayer to illustrate our proposal through first-principles calculations. It is found that half-metallic properties can be achieved in CrSBr within an appropriate electric field range, and the corresponding amplitude of electric field intensity can be realized experimentally. Janus monolayer Cr2S2BrI is constructed, which possesses a built-in electric field due to broken horizontal mirror symmetry. However, Cr2S2BrI without and with an applied external electric field is always a FM semiconductor. A possible memory device is also proposed based on the CrSBr monolayer. Our work will stimulate the application of 2D FM CrSBr in future spintronic nanodevices.

Comprehensive evaluation of carbon sequestration potential of landscape tree species and its influencing factors analysis: implications for urban green space management.

BACKGROUND: Continuous increasing carbon dioxide (CO2) has aggravated global warming and promoted urban tree planting projects for many countries. So it's imperative to select high carbon sequestering landscape tree species while considering their aesthetic values of urban green space. RESULTS: 32 tree species were selected as test objects which were commonly used in landscaping in Zhengzhou, a typical northern city of China. To assess the comprehensive carbon sequestration potential of landscape tree species in different plant configuration types, we simultaneously considered their daily net carbon sequestration per unit leaf area (wCO2), daily net carbon sequestration per unit land area (WCO2) and daily net carbon sequestration of the whole plant (QCO2) through cluster analysis. Besides that, we found out the key factors affecting carbon sequestration potential of landscape tree species by redundancy analysis. CONCLUSION: Populus, P Stenoptera, P. acerifolia among large arbors (LA), V odoratissimum, P. Serratifolia, S. oblata among small arbors (SA), and B sinica var. Parvifolia, B. Megistophylla, L quihoui among shrubs (S) were recommended for local urban green space management. Photosynthetic rate (Pn), crown area (CA) and leaf area index (LAI) were the key factors which affected the comprehensive carbon sequestration potential both for LA, SA and S.

Effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region.

The effect of temperature on the dynamic parameters of silty clay in a seasonally frozen region was assessed using a GDS dynamic triaxial test system. The strength parameters, dynamic elastic modulus, damping ratio, and other dynamic parameters of the soil samples were analyzed under different temperature conditions. The results demonstrated that the shear strength parameters (internal friction angle and cohesion) of the silty clay under a dynamic load increased significantly with decreasing temperature, and the internal friction angle increased sharply below 0 °C. The dynamic elastic modulus increased as the temperature decreased and changed significantly in the ice-water phase change region. The slope of the dynamic stress-strain curve of the soil sample increased significantly with decreasing temperature. As the temperature decreased, the damping ratio reduced, and the ability of the soil to absorb seismic waves declines. The research results provide new data and information to guide construction projects in seasonally frozen region.

Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer.

In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.

Experimental study on soil-water characteristics and strength characteristics of complete-intense weathering mudstone in seasonal frozen area.

To study the soil-water characteristics and shear strength of unsaturated complete-intense weathering mudstone, the soil-water characteristic curve of complete-intense weathering mudstone and the matric suction of mudstone samples under natural state were measured. This measurement was through a soil-water characteristic test using a pressure plate instrument. Based on the results of soil-water characteristic test, an unsaturated (saturated) triaxial shear test was carried out. Under different temperatures and confining pressure conditions, the shear strength and deformation characteristics of complete-intense weathering mudstone under natural water content and saturation conditions were investigated. The results show that the percentage of silt and clay in unsaturated complete-intense weathering mudstone in natural state is relatively high, with the mudstone having less sand, and a weak permeability and exhibiting a significant capillary phenomenon. The complete-intense weathering mudstone with a natural moisture content of 19.15% has a matric suction of 210 kPa. When the temperature is constant, the shear stress of the sample increases with the increase of confining pressure. When the temperature decreases from 0 to -20°C, the influence of confining pressure on the rock samples gradually decreases. The rock sample has the property of strain hardening during shearing. Under the same matric suction, the total cohesion increases with the decrease of temperature. At a positive temperature, the effective internal friction angle increases with the decrease of temperature. At a negative temperature, the lower the temperature, the smaller the effective internal friction angle. The test of shear strength parameters of saturated complete-intense weathering mudstone is simple and conservative. In practical engineering, the basic properties of unsaturated complete-intense weathering mudstone can be predicted by testing the shear strength parameters of saturated complete-intense weathering mudstone. The results of the study are important for better understanding the nature of unsaturated complete-intense weathering mudstone and improving the safety of engineering construction in complete-intense weathering mudstone areas.

Semi-supervised super-resolution of diffusion-weighted images based on multiple references.

Spatial resolution of diffusion tensor images is usually compromised to accelerate the acquisitions, and the state-of-the-art (SOTA) image super-resolution (SR) reconstruction methods are commonly based on supervised learning models. Considering that matched low-resolution (LR) and high-resolution (HR) diffusion-weighted (DW) image pairs are not readily available, we propose a semi-supervised DW image SR reconstruction method based on multiple references (MRSR) extracted from other subjects. In MRSR, the prior information of multiple HR reference images is migrated into a residual-like network to assist SR reconstruction of DW images, and a CycleGAN-based semi-supervised strategy is used to train the network with 30% matched and 70% unmatched LR-HR image pairs. We evaluate the performance of the MRSR by comparing against SOTA methods on an HCP dataset in terms of the quality of reconstructed DW images and diffusion metrics. MRSR achieves the best performance, with the mean PSNR/SSIM of DW images being improved by at least 14.3%/28.8% and 1%/1.4% respectively relative to SOTA unsupervised and supervised learning methods, and with the fiber orientations deviating from the ground truth by about 6.28° on average, the RMSEs of fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity being 3.0%, 4.6%, 5.7% and 4.5% respectively relative to the ground truth. We validate the effectiveness of the proposed network structure, multiple-reference and CycleGAN-based semi-supervised learning strategies for SR reconstruction of diffusion tensor images through the ablation studies. The proposed method allows us to achieve SR reconstruction for diffusion tensor images with a limited number of matched image pairs.

Ultrathin Hydrogel Films toward Breathable Skin-Integrated Electronics.

On-skin electronics that offer revolutionary capabilities in personalized diagnosis, therapeutics, and human-machine interfaces require seamless integration between the skin and electronics. A common question remains whether an ideal interface can be introduced to directly bridge thin-film electronics with the soft skin, allowing the skin to breathe freely and the skin-integrated electronics to function stably. Here, an ever-thinnest hydrogel is reported that is compliant to the glyphic lines and subtle minutiae on the skin without forming air gaps, produced by a facile cold-lamination method. The hydrogels exhibit high water-vapor permeability, allowing nearly unimpeded transepidermal water loss and free breathing of the skin underneath. Hydrogel-interfaced flexible (opto)electronics without causing skin irritation or accelerated device performance deterioration are demonstrated. The long-term applicability is recorded for over one week. With combined features of extreme mechanical compliance, high permeability, and biocompatibility, the ultrathin hydrogel interface promotes the general applicability of skin-integrated electronics.

Spatial engineering of E. coli with addressable phase-separated RNAs.

Biochemical processes often require spatial regulation and specific microenvironments. The general lack of organelles in bacteria limits the potential of bioengineering complex intracellular reactions. Here, we demonstrate synthetic membraneless organelles in Escherichia coli termed transcriptionally engineered addressable RNA solvent droplets (TEARS). TEARS are assembled from RNA-binding protein recruiting domains fused to poly-CAG repeats that spontaneously drive liquid-liquid phase separation from the bulk cytoplasm. Targeting TEARS with fluorescent proteins revealed multilayered structures with composition and reaction robustness governed by non-equilibrium dynamics. We show that TEARS provide organelle-like bioprocess isolation for sequestering biochemical pathways, controlling metabolic branch points, buffering mRNA translation rates, and scaffolding protein-protein interactions. We anticipate TEARS to be a simple and versatile tool for spatially controlling E. coli biochemistry. Particularly, the modular design of TEARS enables applications without expression fine-tuning, simplifying the design-build-test cycle of bioengineering.

A piezoelectric quantum spin Hall insulator VCClBr monolayer with a pure out-of-plane piezoelectric response.

The combination of piezoelectricity with a nontrivial topological insulating phase in two-dimensional (2D) systems, namely piezoelectric quantum spin Hall insulators (PQSHI), is intriguing for exploring novel topological states toward the development of high-speed and dissipationless electronic devices. In this work, we predict a PQSHI Janus monolayer VCClBr constructed from VCCl2, which is dynamically, mechanically and thermally stable. In the absence of spin orbital coupling (SOC), VCClBr is a narrow gap semiconductor with a gap value of 57 meV, which is different from Dirac semimetal VCCl2. The gap of VCClBr is due to a built-in electric field caused by asymmetrical upper and lower atomic layers, which is further confirmed by the external-electric-field induced gap in VCCl2. When including SOC, the gap of VCClBr is increased to 76 meV, which is larger than the thermal energy of room temperature (25 meV). The VCClBr is a 2D topological insulator (TI), which is confirmed by Z2 topological invariant and nontrivial one-dimensional edge states. It is proved that the nontrivial topological properties of VCClBr are robust against strain (biaxial and uniaxial cases) and external electric fields. Due to broken horizontal mirror symmetry, only an out-of-plane piezoelectric response can be observed, when a biaxial or uniaxial in-plane strain is applied. The predicted piezoelectric strain coefficients d31 and d32 are -0.425 pm V-1 and -0.219 pm V-1, respectively, and they are higher than or compared with those of many 2D materials. Finally, Janus monolayer VCFBr and VCFCl (dynamically unstable) are also constructed, and they are still PQSHIs. Moreover, the d31 and d32 of VCFBr and VCFCl are higher than those of VCClBr, and the d31 (absolute value) of VCFBr is larger than one. According to out-of-plane piezoelectric coefficients of VCXY (X ≠ Y = F, Cl and Br), CrX1.5Y1.5 (X = F, Cl and Br; Y = I) and NiXY (X ≠ Y = Cl, Br and I), it is concluded that the size of the out-of-plane piezoelectric coefficient has a positive relation with the electronegativity difference of X and Y atoms. Our studies enrich the diversity of Janus 2D materials, and open a new avenue in the search for PQSHI with a large out-of-plane piezoelectric response, which provides a potential platform in nanoelectronics.

2D Windmill-like Ln-Containing Organophosphonate-Based Polyoxomolybdates: Synthesis, Characterization, Fluorescence, and Magnetism.

By integration of {Ln(H2O)6}3+ into organophosphonate-based polyoxometalates, three Ln-containing organophosphonate-functionalized polyoxomolybdates Na1.5H1.5[{Ln(H2O)6}2{(Mo3O8)(O3PC(C3H6NH3)OPO3)}4]·(CH3CO2)·43H2O (Ln = Eu (1), Tb (2), and Dy (3)) are successfully prepared and systematically characterized. The X-ray crystallography analyses display complexes 1-3 crystallize in the C2/c space group of the monoclinic system and compose several distinctive tetramer windmill-like compounds that further assemble into two-dimensional (2D) frameworks associated with the {Ln(H2O)6}3+ core. The fluorescence spectra of 1-3 show red, green, and chartreuse emissions, respectively, originating in the typical f-f transitions of Ln3+ ions. More interestingly, complex 3 shows the field-induced single-molecule magnet (SMM) properties, resulting from the fact that [(Mo3O8)4{O3PC(C3H6NH3)OPO3}4]8- offers excellent magnetic isolation for Dy3+ ions by the nearest Dy1···Dy2 distance of 11.207 Å. The study demonstrates that the incorporation of {Ln(H2O)6}3+ into organophosphonate-based polyoxomolybdates is an effective synthetic strategy in implementing late-model opto-magnetic materials.

Local neural-network-weighted models for occurrence and number of down wood in natural forest ecosystem.

The natural forest ecosystem has been affected by wind storms for years, which have caused several down wood (DW) and dramatically modified the fabric and size. Therefore, it is very important to explain the forest system by quantifying the spatial relationship between DW and environmental parameters. However, the spatial non-stationary characteristics caused by the terrain and stand environmental changes with distinct gradients may lead to an incomplete description of DW, the local neural-network-weighted models of geographically neural-network-weighted (GNNWR) models are introduced here. To verify the validity of models, our DW and environmental factors were applied to investigate of occurrence of DW and number of DW to establish the generalized linear (logistic and Poisson) models, geographically weighted regression (GWLR and GWPR) models and GNNWR (GNNWLR and GNNWPR) models. The results show that the GNNWR models show great advantages in the model-fitting performance, prediction performance, and the spatial Moran's I of model residuals. In addition, GNNWR models can combine the geographic information system technology for accurately expressing the spatial distribution of DW relevant information to provide the key technology that can be used as the basis for human decision-making and management planning.

Architecting Hierarchical WO3 Agglomerates Assembled With Straight and Parallel Aligned Nanoribbons Enabling High Capacity and Robust Stability of Lithium Storage.

The pursuit of electrochemical energy storage has led to a pressing need on materials with high capacities and energy densities; however, further progress is plagued by the restrictive capacity (372 mAh g-1) of conventional graphite materials. Tungsten trioxide (WO3)-based anodes feature high theoretical capacity (693 mAh g-1), suitable potential, and affordable cost, arousing ever-increasing attention and intense efforts. Nonetheless, developing high-performance WO3 electrodes that accommodate lithium ions remains a daunting challenge on account of sluggish kinetics characteristics and large volume strain. Herein, the well-designed hierarchical WO3 agglomerates assembled with straight and parallel aligned nanoribbons are fabricated and evaluated as an anode of lithium-ion batteries (LIBs), which exhibits an ultra-high capacity and excellent rate capability. At a current density of 1,000 mA g-1, a reversible capacity as high as 522.7 mAh g-1 can be maintained after 800 cycles, corresponding to a high capacity retention of ∼80%, demonstrating an exceptional long-durability cyclic performance. Furthermore, the mechanistic studies on the lithium storage processes of WO3 are probed, providing a foundation for further optimizations and rational designs. These results indicate that the well-designed hierarchical WO3 agglomerates display great potential for applications in the field of high-performance LIBs.

Systematic mapping of cell wall mechanics in the regulation of cell morphogenesis.

Walled cells of plants, fungi, and bacteria come with a large range of shapes and sizes, which are ultimately dictated by the mechanics of their cell wall. This stiff and thin polymeric layer encases the plasma membrane and protects the cells mechanically by opposing large turgor pressure derived mechanical stresses. To date, however, we still lack a quantitative understanding for how local and/or global mechanical properties of the wall support cell morphogenesis. Here, we combine subresolution imaging and laser-mediated wall relaxation to quantitate subcellular values of wall thickness (h) and bulk elastic moduli (Y) in large populations of live mutant cells and in conditions affecting cell diameter in the rod-shaped model fission yeast. We find that lateral wall stiffness, defined by the surface modulus, σ = hY, robustly scales with cell diameter. This scaling is valid across tens of mutants spanning various functions-within the population of individual isogenic strains, along single misshaped cells, and even across the fission yeasts clade. Dynamic modulations of cell diameter by chemical and/or mechanical means suggest that the cell wall can rapidly adapt its surface mechanics, rendering stretched wall portions stiffer than unstretched ones. Size-dependent wall stiffening constrains diameter definition and limits size variations; it may also provide an efficient means to keep elastic strains in the wall below failure strains, potentially promoting cell survival. This quantitative set of data impacts our current understanding of the mechanics of cell walls and its contribution to morphogenesis.

Controllable Sulfur, Nitrogen Co-doped Porous Carbon for Ethylbenzene Oxidation: The Role of Nano-CaCO3.

Heteroatom-doped porous carbon materials have exhibited promising applications in various fields. In this work, sulfur, nitrogen co-doped carbon materials (SNCs) with abundant pore structure were prepared by pyrolysis of sulfur, nitrogen-containing porous organic polymers (POPs) mixed with nano-CaCO3 at high temperature. Among the resultant materials, SNC-Ca-850 possesses a relatively high level of doped heteroatoms and exhibits an excellent catalytic performance for the selective oxidation of benzylic C-H bonds. It is noteworthy that nano-CaCO3 increases the doped sulfur content in the synthesized carbon materials to a large extent and impacts the existence modes of sulfur. In addition, it enhances the porous structure and specific surface area of the resultant SNCs significantly. This work provides a viable strategy to promote the doping of sulfur into carbon materials during the pyrolysis process.

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation.

B-cell receptor-associated protein 31 (BAP31) is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein that has been found to be overexpressed in gastric intestinal-type adenocarcinoma. We first studied the relationship of BAP31 with 84 kinds of tumor-associated antigens and found that BAP31 can specifically interact with and regulate the proteasome degradation of the cyclin kinase inhibitor p27kip1 , which is one of the most frequently dysregulated tumor suppressor proteins in human cancers. Therefore, we screened antibodies against BAP31 from a human VH single-domain antibody library and expressed the antibodies intracellularly. It was found that one of the intrabodies (VH-D1) specifically inhibited p27kip1 proteasome degradation, possibly by blocking the combination of BAP31 with p27kip1 . VH-D1 displayed therapeutic effects, as it was able to reduce the growth of human gastric cancer (GC) cell xenografts in nude mice. This effect was due to inhibition of the proliferation and subsequent activation of caspase-dependent apoptosis. Thus, BAP31 is a potential target for the suppression of GC via an intrabody-based approach.