Multimodal probing of T-cell recognition with hexapod heterostructures.

Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.

The response of non-point source pollution to climate change in an orchard-dominant coastal watershed.

China is the largest global orchard distribution area, where high fertilization rates, complex terrain, and uncertainties associated with future climate change present challenges in managing non-point source pollution (NPSP) in orchard-dominant growing areas (ODGA). Given the complex processes of climate, hydrology, and soil nutrient loss, this study utilized an enhanced Soil and Water Assessment Tool model (SWAT-CO2) to investigate the impact of future climate on NPSP in ODGA in a coastal basin of North China. Our investigation focused on climate-induced variations in hydrology, nitrogen (N), and phosphorus (P) losses in soil, considering three Coupled Model Intercomparison Project phase 6 (CMIP6) climate scenarios: SSP1-2.6, SSP2-4.5, and SSP5-8.5. Research results indicated that continuous changes in CO2 levels significantly influenced evapotranspiration (ET) and water yield in ODGA. Influenced by sandy soils, nitrate leaching through percolation was the principal pathway for N loss in the ODGA. Surface runoff was identified as the primary pathway for P loss. Compared to the reference period (1971-2000), under three future climate scenarios, the increase in precipitation of ODGA ranged from 15% to 28%, while the growth rates of P loss and surface runoff were the most significant, both exceeding 120%. Orchards in the northwest basin proved susceptible to nitrate leaching, while others were more sensitive to N and P losses via surface runoff. Implementing targeted strategies, such as augmenting organic fertilizer usage and constructing terraced fields, based on ODGA's response characteristics to future climate, could effectively improve the basin's environment.

Response of hydrology and nutrient losses to different extreme rainfall conditions in a coastal watershed influenced by orchards.

Global warming is altering the frequency of extreme rainfall events and introducing uncertainties for non-point source pollution (NPSP). This research centers on orchard-influenced planting areas (OIPA) in the Wulong River Watershed of Shandong Province, China, which are known for their heightened nitrogen (N) and phosphorus (P) pollution. Leveraging meteorological data from both historical (1989-2018) and projected future periods (2041-2100), this research identified five extreme rainfall indices (ERI): R10 (moderate rain), R20 (heavy rain), R50 (rainstorm), R95p (Daily rainfall between the 95th and 99th percentile of the rainfall), and R99p (>99th percentile). Utilizing an advanced watershed hydrological model, SWAT-CO2, this study carried out a comparison between ERI and average conditions and evaluated the effects of ERI on the hydrology and nutrient losses in this coastal watershed. The findings revealed that the growth multiples of precipitation in the OIPA for five ERI varied between 16 and 59 times for the historical period and 14 to 65 times for future climate scenarios compared to the average conditions. The most pronounced increases in surface runoff and total phosphorus (TP) loss were observed with R50, R95p, and R99p, showing growth multiples as high as 352 and 330 times, and total nitrogen (TN) growth multiples varied between 4.6 and 30.3 times. The contribution rates of R50 and R99p for surface runoff and TP loss in the OIPA during all periods exceeded 55%, however, TN exhibited the opposite trend, primarily due to the dominated NO3-N leaching in the sandy soil. This research revealed how the OIPA reacts to different ERI and pinpointed essential elements influencing water and nutrient losses.

Recent advances in bioelectronics chemistry.

Research in bioelectronics is highly interdisciplinary, with many new developments being based on techniques from across the physical and life sciences. Advances in our understanding of the fundamental chemistry underlying the materials used in bioelectronic applications have been a crucial component of many recent discoveries. In this review, we highlight ways in which a chemistry-oriented perspective may facilitate novel and deep insights into both the fundamental scientific understanding and the design of materials, which can in turn tune the functionality and biocompatibility of bioelectronic devices. We provide an in-depth examination of several developments in the field, organized by the chemical properties of the materials. We conclude by surveying how some of the latest major topics of chemical research may be further integrated with bioelectronics.

Synthesis of Metal-Capped Semiconductor Nanowires from Heterodimer Nanoparticle Catalysts.

Semiconductor nanowires (NWs) capped with metal nanoparticles (NPs) show multifunctional and synergistic properties, which are important for applications in the fields of catalysis, photonics, and electronics. Conventional colloidal syntheses of this class of hybrid structures require complex sequential seeded growth, where each section requires its own set of growth conditions, and methods for preparing such wires are not universal. Here, we report a new and general method for synthesizing metal-semiconductor nanohybrids based on particle catalysts, prepared by scanning probe block copolymer lithography, and chemical vapor deposition. In this process, metallic heterodimer NPs were used as catalysts for NW growth to form semiconductor NWs capped with metallic particles (Au, Ag, Co, Ni). Interestingly, the growth processes for NWs on NPs are regioselective and controlled by the chemical composition of the metallic heterodimer used. Using a systematic experimental approach, paired with density functional theory calculations, we were able to postulate three different growth modes, one without precedent.

A Survey of Knowledge Graph Reasoning on Graph Types: Static, Dynamic, and Multi-Modal.

Knowledge graph reasoning (KGR), aiming to deduce new facts from existing facts based on mined logic rules underlying knowledge graphs (KGs), has become a fast-growing research direction. It has been proven to significantly benefit the usage of KGs in many AI applications, such as question answering, recommendation systems, and etc. According to the graph types, existing KGR models can be roughly divided into three categories, i.e., static models, temporal models, and multi-modal models. Early works in this domain mainly focus on static KGR, and recent works try to leverage the temporal and multi-modal information, which are more practical and closer to real-world. However, no survey papers and open-source repositories comprehensively summarize and discuss models in this important direction. To fill the gap, we conduct a first survey for knowledge graph reasoning tracing from static to temporal and then to multi-modal KGs. Concretely, the models are reviewed based on bi-level taxonomy, i.e., top-level (graph types) and base-level (techniques and scenarios). Besides, the performances, as well as datasets, are summarized and presented. Moreover, we point out the challenges and potential opportunities to enlighten the readers. The corresponding open-source repository is shared on GitHub https://github.com/LIANGKE23/Awesome-Knowledge-Graph-Reasoning.

SARF: Aliasing Relation-Assisted Self-Supervised Learning for Few-Shot Relation Reasoning.

Few-shot relation reasoning on knowledge graphs (FS-KGR) is an important and practical problem that aims to infer long-tail relations and has drawn increasing attention these years. Among all the proposed methods, self-supervised learning (SSL) methods, which effectively extract the hidden essential inductive patterns relying only on the support sets, have achieved promising performance. However, the existing SSL methods simply cut down connections between high-frequency and long-tail relations, which ignores the fact, i.e., the two kinds of information could be highly related to each other. Specifically, we observe that relations with similar contextual meanings, called aliasing relations (ARs), may have similar attributes. In other words, the ARs of the target long-tail relation could be in high-frequency, and leveraging such attributes can largely improve the reasoning performance. Based on the interesting observation above, we proposed a novel Self-supervised learning model by leveraging Aliasing Relations to assist FS-KGR, termed . Specifically, we propose a graph neural network (GNN)-based AR-assist module to encode the ARs. Besides, we further provide two fusion strategies, i.e., simple summation and learnable fusion, to fuse the generated representations, which contain extra abundant information underlying the ARs, into the self-supervised reasoning backbone for performance enhancement. Extensive experiments on three few-shot benchmarks demonstrate that achieves state-of-the-art (SOTA) performance compared with other methods in most cases.

A soil-inspired dynamically responsive chemical system for microbial modulation.

Interactions between the microbiota and their colonized environments mediate critical pathways from biogeochemical cycles to homeostasis in human health. Here we report a soil-inspired chemical system that consists of nanostructured minerals, starch granules and liquid metals. Fabricated via a bottom-up synthesis, the soil-inspired chemical system can enable chemical redistribution and modulation of microbial communities. We characterize the composite, confirming its structural similarity to the soil, with three-dimensional X-ray fluorescence and ptychographic tomography and electron microscopy imaging. We also demonstrate that post-synthetic modifications formed by laser irradiation led to chemical heterogeneities from the atomic to the macroscopic level. The soil-inspired material possesses chemical, optical and mechanical responsiveness to yield write-erase functions in electrical performance. The composite can also enhance microbial culture/biofilm growth and biofuel production in vitro. Finally, we show that the soil-inspired system enriches gut bacteria diversity, rectifies tetracycline-induced gut microbiome dysbiosis and ameliorates dextran sulfate sodium-induced rodent colitis symptoms within in vivo rodent models.

Biology-guided engineering of bioelectrical interfaces.

Bioelectrical interfaces that bridge biotic and abiotic systems have heightened the ability to monitor, understand, and manipulate biological systems and are catalyzing profound progress in neuroscience research, treatments for heart failure, and microbial energy systems. With advances in nanotechnology, bifunctional and high-density devices with tailored structural designs are being developed to enable multiplexed recording or stimulation across multiple spatial and temporal scales with resolution down to millisecond-nanometer interfaces, enabling efficient and effective communication with intracellular electrical activities in a relatively noninvasive and biocompatible manner. This review provides an overview of how biological systems guide the design, engineering, and implementation of bioelectrical interfaces for biomedical applications. We investigate recent advances in bioelectrical interfaces for applications in nervous, cardiac, and microbial systems, and we also discuss the outlook of state-of-the-art biology-guided bioelectrical interfaces with high biocompatibility, extended long-term stability, and integrated system functionality for potential clinical usage.

Effects of Comprehensive Nursing Based on Orem's Self-Care Theory on Symptom Improvement and Pregnancy Outcome in Patients with Antiphospholipid Syndrome: A Retrospective Cohort Study.

Objective: A retrospective cohort study was conducted to explore the effects of comprehensive nursing based on Orem's self-care theory on symptom improvement and pregnancy outcomes in patients with antiphospholipid syndrome (APS). Methods: Sixty patients with antiphospholipid antibody syndrome treated in our hospital from February 2019 to April 2021 were enrolled. The control group received comprehensive nursing, while the study group received comprehensive nursing based on Orem's self-care theory. Nursing satisfaction, self-nursing ability, anxiety score, social support status, pregnancy outcome, and the score of life quality were compared between the two groups. Results: First of all, we compared the nursing satisfaction, the study group was very satisfied in 23 cases, satisfactory in 5 cases, general in 2 cases, the satisfaction rate was 100.00%. While in the control group, 11 cases were very satisfied, 10 cases were satisfied, 4 cases were general, and 5 cases were dissatisfied, the satisfaction rate was 83.33%. The nursing satisfaction in the study group was higher compared to the control group (P < 0.05). Secondly, the self-concept, sense of self-care responsibility, self-nursing skills, health knowledge, and total score of the study group were higher compared to the control group (P < 0.05). After intervention, the anxiety scores of the two groups decreased. Compared between the two groups, the anxiety scores of the study group before intervention and 1 week, 2 weeks, 3 weeks, and 4 weeks after intervention were lower compared to the control group (P < 0.05). The comparison of social support showed that the scores of objective support, subjective support, utilization of support, and total score of social support in the study group were higher compared to the control group (P < 0.05). The number of abortions in the control group was lower compared to the control group, and the number of full-term deliveries was higher compared to the control group (P < 0.05). Finally, we compared the scores of life quality. After nursing, the scores of life quality of the two groups increased. Of note, the scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group (P < 0.05). Conclusion: Comprehensive nursing for patients with APS based on Orem's self-care theory can effectively improve clinical symptoms and pregnancy outcome and play a positive role in facilitating patients' nursing satisfaction and self-nursing ability, which can also effectively strengthen mental health and social support, this nursing model is worth popularizing in clinic.

Outcome measures of palliative care programs and interventions implemented in nursing homes: a scoping review protocol.

OBJECTIVE: This scoping review aims to identify and map the outcomes reported from evaluations that measure the effectiveness and acceptability of palliative care programs and interventions in residential aged care facilities. INTRODUCTION: As the population ages, there is increasing attention on implementing new interventions and programs to improve palliative care in residential aged care facilities. However, there is no standard evaluation for intervention implementation. Mapping the outcome measures used in evaluations of diverse palliative care interventions in residential aged care facilities has not been explored recently. INCLUSION CRITERIA: This review will consider studies involving older adults (aged 50 years and above) in any country living and receiving care in residential aged care facilities. This review will exclude literature that focuses on other age groups, and people receiving palliative care in other care settings, such as hospitals, palliative care inpatient units, sheltered housing, cancer centers, own homes, and hospices. METHODS: This scoping review will follow the JBI methodology for scoping reviews. This scoping review will identify both published and unpublished (eg, gray literature) primary studies, as well as reviews. The databases to be searched for published studies will include MEDLINE, Emcare, ProQuest, Embase, PsycINFO, Web of Science, Scopus, and the Cochrane Library. The search will be limited to evidence published in English from 2008 to the present. Visual, tabular, and accompanying narrative summaries will be used to present the results.

Gold-Decorated Silicon Nanowire Photocatalysts for Intracellular Production of Hydrogen Peroxide.

Hydrogen peroxide (H2O2) plays diverse biological roles, and its effects in part depend on its spatiotemporal presence, in both intra- and extracellular contexts. A full understanding of the physiological effects of H2O2 in both healthy and disease states is hampered by a lack of tools to controllably produce H2O2. Here, we address this issue by showing visible-light-induced production of exogenous H2O2 by free-standing, gold-decorated silicon nanowires internalized in human umbilical vein endothelial cells. We further show that the photocatalytic production of H2O2 is a general phenomenon of gold-silicon hybrid materials and is enhanced upon annealing.

Micelle-enabled self-assembly of porous and monolithic carbon membranes for bioelectronic interfaces.

Real-world bioelectronics applications, including drug delivery systems, biosensing and electrical modulation of tissues and organs, largely require biointerfaces at the macroscopic level. However, traditional macroscale bioelectronic electrodes usually exhibit invasive or power-inefficient architectures, inability to form uniform and subcellular interfaces, or faradaic reactions at electrode surfaces. Here, we develop a micelle-enabled self-assembly approach for a binder-free and carbon-based monolithic device, aimed at large-scale bioelectronic interfaces. The device incorporates a multi-scale porous material architecture, an interdigitated microelectrode layout and a supercapacitor-like performance. In cell training processes, we use the device to modulate the contraction rate of primary cardiomyocytes at the subcellular level to target frequency in vitro. We also achieve capacitive control of the electrophysiology in isolated hearts, retinal tissues and sciatic nerves, as well as bioelectronic cardiac sensing. Our results support the exploration of device platforms already used in energy research to identify new opportunities in bioelectronics.

Laser writing of nitrogen-doped silicon carbide for biological modulation.

Conducting or semiconducting materials embedded in insulating polymeric substrates can be useful in biointerface applications; however, attainment of this composite configuration by direct chemical processes is challenging. Laser-assisted synthesis has evolved as a fast and inexpensive technique to prepare various materials, but its utility in the construction of biophysical tools or biomedical devices is less explored. Here, we use laser writing to convert portions of polydimethylsiloxane (PDMS) into nitrogen-doped cubic silicon carbide (3C-SiC). The dense 3C-SiC surface layer is connected to the PDMS matrix via a spongy graphite layer, facilitating electrochemical and photoelectrochemical activity. We demonstrate the fabrication of arbitrary two-dimensional (2D) SiC-based patterns in PDMS and freestanding 3D constructs. To establish the functionality of the laser-produced composite, we apply it as flexible electrodes for pacing isolated hearts and as photoelectrodes for local peroxide delivery to smooth muscle sheets.

Structured silicon for revealing transient and integrated signal transductions in microbial systems.

Bacterial response to transient physical stress is critical to their homeostasis and survival in the dynamic natural environment. Because of the lack of biophysical tools capable of delivering precise and localized physical perturbations to a bacterial community, the underlying mechanism of microbial signal transduction has remained unexplored. Here, we developed multiscale and structured silicon (Si) materials as nongenetic optical transducers capable of modulating the activities of both single bacterial cells and biofilms at high spatiotemporal resolution. Upon optical stimulation, we capture a previously unidentified form of rapid, photothermal gradient-dependent, intercellular calcium signaling within the biofilm. We also found an unexpected coupling between calcium dynamics and biofilm mechanics, which could be of importance for biofilm resistance. Our results suggest that functional integration of Si materials and bacteria, and associated control of signal transduction, may lead to hybrid living matter toward future synthetic biology and adaptable materials.

[Spectroscopy research on synthesis of new desilication reagent-calcium hydroferrocarbonate].

For removing silica from high concentration medium after digestion of the diasporic bauxite by sub-molten salt, the research used calcium hydroferrocarbonate with the new desilication reagent. In the reaction, calcium carbonate, calcium hydroxide and calcium ferrite were by-product, therefore the reaction factors showed significant influence on the synthesis and disilicating efficiency. To explore the synthesis mechanism and optimize the reaction factors, the composition of the intermediate obtained from the synthesis reaction was investigated through the combination of FTIR, ICP-AES and desilication reaction. The FTIR and desilication reaction results revealed that calcium hydroferrocarbonate is metastable compound in solution, and the reaction temperature and reaction time have significant influence on the systhesis. With the temperature and reaction time increasing, the content of calcium hydroferrocarbonate in the composition first increased and then reduced. The optimal factors were: temperature of 30 degrees C, reaction time of 16 hours, the liquid to solid mass ratio of 20 and rpm of 500 r x min(-1). The crystal structure of calcium hydroferrocarbonate was investigated, and was found to be rhombohedral, including H2O bond, -OH bond and Fe-O bond.

Diversity of Serotype, Genotype, and Antibiotic Susceptibility of Salmonella Prevalent in Pickled Ready-to-Eat Meat.

Pickled ready-to-eat meat (PRTEM) is a meat product that is treated with various seasonings and then cooked. PRTEM is a popular food consumed mostly in China and some Asian countries. Since this food is considered 'ready to eat', once it is contaminated by foodborne pathogens such as Salmonella, the prospect for significant morbidity, mortality, and immeasurable economic losses can occur. Here we investigated the prevalence and concentration of Salmonella in 107 PRTEM samples collected from Shaanxi, China during 2015-2016. Furthermore, we analyzed the serotype, antibiotic susceptibility, and presence of antibiotic resistance genes and amino acid mutations in 219 Salmonella isolates, followed by subtyping of 115 representative isolates. The average detection rate of Salmonella-positive PRTEM was 58.9%, and the average most probable number (MPN) of Salmonella in positive samples was 2.27 logMPN per gram of sample (range: 2.10-2.43). Ten serotypes were identified from the 219 Salmonella isolates, with S. Thompson (37.9%) and S. Indiana (20.5%) being predominant. The remaining serotypes were S. Typhi (7.8%), S. Typhimurium (7.3%), S. Mbandaka (6.9%), S. Albany (6.4%), S. Blockley (5.5%), S. Infantis (4.1%), S. Escanaba (3.2%), and S. Dusseldorf (0.5%). All isolates were resistant to ceftiofur (100%), while most of them were resistant to ciprofloxacin (99.1%), amoxicillin-clavulanic acid (97.7%), trimethoprim-sulfamethoxazole (96.4%), ampicillin (92.3%), sulfisoxazole (92.2%), tetracyclines (90.4%), and nalidixic acid (90.4%), respectively. A single mutation of Ser83Phe (27.1%) and double mutations of Ser83Phe-Asp87Gly (25.9%) in GyrA were detected in 85 isolates, whereas mutations of Thr57Ser (63.9%) and Ser80Arg (36.1%) in ParC were detected in 122 isolates. qnrB, oqxAB, aac(6')-Ib, and qnrA were present in 50 (22.8%), 48 (21.9%), 26 (11.9%), and 1 (0.5%) isolate(s), respectively. Pulse field gel electrophoresis results revealed that those isolates recovered from the same type of PRTEM or the same sampling place shared identical or similar DNA profiles, antibiotic resistance phenotypes, and even plasmid-mediated quinolone resistance encoding genes. The findings indicate that Salmonella is commonly prevalent in PRTEMs at high concentrations in Shaanxi, China. More attention should be paid to the processing and storage of this ready-to-eat food to prevent bacterial contamination and foodborne outbreaks.

Nongenetic optical neuromodulation with silicon-based materials.

Optically controlled nongenetic neuromodulation represents a promising approach for the fundamental study of neural circuits and the clinical treatment of neurological disorders. Among the existing material candidates that can transduce light energy into biologically relevant cues, silicon (Si) is particularly advantageous due to its highly tunable electrical and optical properties, ease of fabrication into multiple forms, ability to absorb a broad spectrum of light, and biocompatibility. This protocol describes a rational design principle for Si-based structures, general procedures for material synthesis and device fabrication, a universal method for evaluating material photoresponses, detailed illustrations of all instrumentation used, and demonstrations of optically controlled nongenetic modulation of cellular calcium dynamics, neuronal excitability, neurotransmitter release from mouse brain slices, and brain activity in the mouse brain in vivo using the aforementioned Si materials. The entire procedure takes ~4-8 d in the hands of an experienced graduate student, depending on the specific biological targets. We anticipate that our approach can also be adapted in the future to study other systems, such as cardiovascular tissues and microbial communities.

Characterization of extended-spectrum ß-lactamases (ESBLs)-producing Salmonella in retail raw chicken carcasses.

Extended-spectrum ß-lactamases (ESBLs)-producing Salmonella is considered a serious concern to public health worldwide. However, limited information is available on ESBLs-producing Salmonella in retail chicken products in China. The objective of this study was to characterize ESBLs-producing Salmonella isolates from retail chickens in China. A total of 890 Salmonella isolates from retail chicken carcasses collected from 4 provinces were firstly screened for ESBLs-production phenotype via the double-disk synergy test method. A total of 96 (10.8%, n=890) ESBLs-producing Salmonella were identified and subjected to PFGE analysis, characterization for the presence of ESBLs encoding genes, transposons, carbapenemase and virulence genes. A total of 59 PFGE profiles were detected in these 96 isolates, among which 57.3% were found to harbor blaTEM-1, whereas 30.2%, 24.0%, 18.8% and 7.3% were carrying blaOXA-1, blaCTX-M-15, blaCTX-M-3 and blaPSE-1 genes, respectively. Moreover, 42 (43.8%) isolates co-carried 2 ESBLs-producing genes, and two (2.1%) isolates co-carried 3 genes. Furthermore, 24 (25.0%) ESBLs-producing isolates carried VIM and 10 (10.4%) carried KPC encoding genes that closely associated with carbapenems resistance. Eighty-eight isolates harbored transposons ranging from 4.2% for Tn903 to 76.0% for Tn21. Out of the 88 Salmonella that harbored transposons, 25%, 22.7%, 23.9%, 10.2% and 1.1% of isolates were found to carry 2, 3, 4, 5 and 6 transposons, respectively. The minimum inhibitory concentration (MIC) values for cephalosporins (ceftriaxone, cefoperazone and cefoxitin) to ESBLs-producing isolates were from 4 to 1024µg/mL, for nalidixic acid were from 64 to 512µg/mL, for fluoroquinolones (ciprofloxacin, levofloxacin and gatifloxacin) were from 4 to 256µg/mL. Twenty-nine virulence genes were detected in the 96 ESBLs-producing isolates with 2.1% harbored spvR (lowest) and 90.6% harbored marT and steB (highest). All isolates carried at least one virulence gene, 83.3% of the isolates co-carried ≥10, 17.7% co-carried ≥15, and 1.0% co-carried 23 virulence genes. Interestingly, 16.7% of the isolates resistant to >12 antibiotics tested and shown to carry >4 transposons and 10 virulence genes. Our findings indicated that ESBLs-producing Salmonella isolated from retail chicken meat in China were highly resistant to antibiotics, frequently harbored transposons, virulence genes, carbapenems hydrolysis enzymes and ESBLs encoding genes. These isolates can pose a significant public health risk.

GATA2 regulates GATA1 expression through LSD1-mediated histone modification.

The dynamic and reversed expression of GATA1 and GATA2 are essential for proper erythroid differentiation. Our previous work demonstrates that LSD1, a histone H3K4 demethylase, represses GATA2 expression at late stage of erythroid differentiation. K562 and MEL cells were used and cultured in Roswell Park Memorial Institute-1640 medium (RPMI) and Dulbecco's modified Eagle's medium (DMEM), respectively. Western blot assay was used to examine the GATA1, GATA2, TAL1, HDAC1, HDAC2, CoREST and ß-actin protein. The immunoprecipitation assay and GST pull-down assay were employed to detect the precipitated protein complexes and investigate the interaction between the proteins. The small interfering RNA (siRNA) and nonspecific control siRNA were synthesized to silence the target genes. Double fluorescence immunostaining was used to observe the association of LSD1 with GATA2 in K562 cells. The results indicated that knockdown of LSD1 in K562 cell causes increased H3K4 di-methylation at GATA1 locus and activates GATA1 expression, demonstrating that LSD1 represses GATA1 expression through LSD1-mediated histone demethylation. Upon induced erythroid differentiation of K562 cells, the interaction between GATA2 and LSD1 is decreased, consistent with a de-repression of GATA1 expression. Meanwhile, the interaction between TAL1 and LSD1 is increased, which forms a complex that efficiently suppresses GATA2 expression. In conclusion, these observations reveal an elegant mechanism to modulate GATA1 and GATA2 expression during erythroid differentiation. While LSD1 mainly forms complex with GATA2 to repress GATA1 expression in hematopoietic progenitor cells, it mostly forms complex with TAL1 to repress GATA2 expression in differentiated cells.