Melanoma, the skin cancer with the highest mortality rate, can be diagnosed at the early stage by detecting unique biomarkers. Over-expressed tyrosinase has been confirmed by dozens of clinical ...studies as an independent factor to evaluate the malignancy of melanoma. Using Enteromorpha Prolifera as the raw material, herein we develop a novel fluorescent probe, ECDY, which can sensitively detect the tyrosinase activity in different types of cells. More importantly, melanoma cells can be specifically distinguished through cell lysate measurements as well as the whole-cell imaging technique. Mechanically, the tyrosine groups on the surface of ECDY can be specifically recognized by tyrosinase and further converted into dopaquinone, which consequently causes the intramolecular fluorescence quenching of the probe through photoinduced electron transfer (PET). Tyrosinase can be detected within 20 min in the solution, and the detection limit is as low as 0.067 U mL−1. For the in vitro demonstration, we evaluate the fluorescence decay of ECDY in response to the intracellular tyrosinase activity within the lysate of various cell lines, including non-cancerous, non-melanoma cancerous, and mouse melanoma ones. The experimental results verify that ECDY can accurately measure the apparent tyrosinase activity in different cell lines and detect melanoma cell lysate specifically. The confocal fluorescence imaging experiments further demonstrate that ECDY can distinguish melanoma cells from others significantly. We believe that ECDY provides a new strategy for the efficient detection of tyrosinase and melanoma cells, and is expected to apply as a clinical diagnosis platform.
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•A fluorescent tyrosinase probe was synthesized using Enteromorpha Prolifera as the raw material.•Tyrosinase in solution at 0.067 U mL−1 can be detected with high selectivity.•The apparent activity of tyrosinase in different cell lines can be evaluated through cell lysate measurement.•The probe can be effectively internalized into various cells and distinguish living melanoma cells from others.
Neoantigens derived from non-synonymous somatic mutations are restricted to malignant cells and are thus considered ideal targets for T cell receptor (TCR)-based immunotherapy. Adoptive transfer of T ...cells bearing neoantigen-specific TCRs exhibits the ability to preferentially target tumor cells while remaining harmless to normal cells. High-avidity TCRs specific for neoantigens expressed on AML cells have been identified in vitro and verified using xenograft mouse models. Preclinical studies of these neoantigen-specific TCR-T cells are underway and offer great promise as safe and effective therapies. Additionally, TCR-based immunotherapies targeting tumor-associated antigens are used in early-phase clinical trials for the treatment of AML and show encouraging anti-leukemic effects. These clinical experiences support the application of TCR-T cells that are specifically designed to recognize neoantigens. In this review, we will provide a detailed profile of verified neoantigens in AML, describe the strategies to identify neoantigen-specific TCRs, and discuss the potential of neoantigen-specific T-cell-based immunotherapy in AML.
Enhancing crop production in the saline regions of the Yellow River Delta (YRD), where shallow saline groundwater is prevalent, hinges on optimizing water and salt conditions in the root zone. This ...study explored the effects of various physical methods on soil water and salt dynamics during the cotton growing season in these saline areas. Three approaches were tested: plastic film mulching (FM), plastic film mulching with an added compacted soil layer (FM+CL), and ridge-furrow planting (RF). The HYDRUS-2D model (Version 3.02) was used to analyze changes in soil water and salt content in the root zone over time. The results showed that subsoil compaction significantly lowered salt build-up in the root zone, especially in the top 20 cm. Film mulching was crucial for reducing water loss in the Yellow River Delta. Crop transpiration increased by 7.0% under FM and 10.5% under FM+CL compared to RF planting. Additionally, FM+CL reduced soil salinity in the top 10 cm by 11.5% at cotton harvest time compared to FM alone. The study concludes that combining film mulching with a soil compaction layer is a promising strategy for local farmers, addressing soil water retention, salt management, and boosting cotton yields.
Arsenic (As) exposure has been a global public health concern for hundreds of millions worldwide. LncRNA APTR (Alu-mediated p21 transcriptional regulator) plays an essential role in tumor growth and ...development. However, its function in arsenic-induced toxicological responses is still unknown. In this study, we found that the expressions of all transcripts and the transcript NR 134251.1 of APTR were increased in a dose-dependent manner in 16HBE cells treated with sodium arsenite (NaAsO2). Silencing the transcript NR 134251.1 of APTR inhibited cell proliferation and induced apoptosis. However, silencing all transcripts of APTR had the opposite function to the transcript NR 134251.1. Then we examined the protein level of the proliferation and apoptosis-related genes after silencing the transcript NR 134251.1 of APTR. The results showed that silencing the transcript NR 134251.1 of APTR up-regulated the expression of transcription factor E2F1 and regulated its downstream genes involved in proliferation and apoptosis, including p53, phospho-p53-S392, phospho-p53-T55, p21, Cyclin D1, PUMA, Fas, Bim, BIK, Caspase-3, Caspase-7, and Cyt-c. In conclusion, arsenic induced APTR expression and the transcript NR 134251.1 of APTR have an opposite function to all transcripts, providing a theoretical basis for the prevention and treatment of arsenic exposure.
Soil fertility can be improved by effectively utilizing agricultural waste. Straw can supply energy and wood ash adds nutrients to improve soil quality. However, few kinds of research have ...investigated the effect of wood ash and straw on soil carbon sequestration and the soil bacterial population, particularly in calcareous soils. The main goal of this current study was to quantify the impact of a combination of wood ash and straw on the indicators described above using stable δ
13
C isotope analyses by applying wheat straw to calcareous soil under a long-term C
4
crop rotation. The incubation experiment included four treatments as follows: (i) no amendment (Control); (ii) amendment with wood ash (W); (iii) amendment with straw (S); and (iv) a combined amendment of straw and wood ash (SW). Our results showed that sequestration of soil inorganic carbon (SIC) in the SW and W treatments was higher (an average of 7.78%) than that in the S and Control treatments. The sequestered soil organic carbon (SOC) in the SW treatment was 1.25-fold greater than that in the S treatment, while there was no evident effect on the SOC content compared with straw alone. The microbial biomass carbon increased under SW by 143.33%, S by 102.23%, and W by 13.89% relative to control. The dissolved organic carbon increased under SW by 112.0%, S by 66.61%, and W by 37.33% relative to the control. The pH and electrical conductivity were higher in the SW and W treatments than in the S treatment and the control. The SW was conducive to maintaining soil enzymatic activities and bacterial diversity. Bacteroidetes and Actinobacteriota were dominant in SW, while the Acidobacteria phyla were dominant in the S treatment. The diversity of bacteria in the soil and community composition of the bacteria were predominantly assessed by the levels of water-soluble K, pH, and electrical conductivity. The incorporation of straw and wood ash is probably more effective at improving SIC and SOC sequestration and ameliorates the soil microhabitat.
We propose cascaded mode-division-multiplexing and time-division-multiplexing passive optical network (MDM-TDM-PON) based on low mode-crosstalk few-mode fiber (FMF) and all-fiber mode ...multiplexer/demultiplexer (MUX/DEMUX), in which optical network units communicate with the optical line terminal utilizing different time slots and specific optical linearly polarized spatial modes. An MDM optical distribution network (ODN) is cascaded with multiple conventional TDM ODNs to effectively extend a larger scale of current commercial PON systems based on TDM. The upgrade from TDM-PON to the cascaded MDM-TDM-PON is simple and cost-effective. No multiple-input-multiple-output (MIMO) digital signal processing is required to eliminate the mode crosstalk. The all-fiber mode MUX/DEMUXs are composed of mode selective couplers, which simultaneously multiplex or demultiplex multiple modes. We experimentally demonstrate MDM-PON transmission over 10 and 55 km two-mode FMFs and cascaded MDM-TDM-PON transmission over a 10-km two-mode FMF and a 10-km standard single-mode fiber with 10-Gb/s optical on-off keying (OOK) signal and direct detection.
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•A novel heparanase-degradable microcarrier targeting tumor cells was developed.•The microcarrier was fabricated through self-assembling processes.•Each component of the microcarrier ...plays multiple roles.
Compared with primary and local tumor, metastasis is more difficult to resect completely and remain the leading cause of death associated with solid tumors. It is therefore pressing to develop effective strategies to prevent and suppress tumor metastasis in its early stages. Heparanase overexpression is significantly associated with increased malignancy and metastasis. Here, we develop a novel heparanase degradable heparin-based microcarrier, HBMA, for specific staining, targeting, and inhibiting tumor cells with high metastatic potential. HBMA is fabricated through self-assembling of three components, positively charged fluorescent gold nanoclusters (KG-AuNCs), heparin polymers (HP), and antisense miRNA-21 oligonucleotides (AM-21), with each component playing multiple roles. Results of confocal microscopy and flow cytometry show that this agent has an excellent capability to label metastatic tumor cells with high selectivity. On the therapeutic side, the results of cell viability assay, wound healing assay, and plate colony formation assay verify that HBMA induces a significant inhibition effect towards the proliferation and migration of the selectively target tumor cells. The heparanase responsive AM-21 delivery, the specific staining, and the efficient tumor cell activity suppression highlight HBMA as a promising cancer theranostic agent to prevent tumor metastasis.
Recently, mode division multiplexing (MDM) has been introduced into optical transmission systems and networks for capacity enhancement. In this letter, we propose a bidirectional passive optical ...network (PON) architecture based on MDM. The bidirectional optical distribution network of the MDM-PON consists of few-mode fiber, passive mode multiplexer/demultiplexer, and few-mode circulators, all of which are characterized by low modal-crosstalk. Signals in different modes are able to be transmitted and received independently for both downstream and upstream transmission. We experimentally demonstrate the bidirectional MDM-PON transmission over 10-km two-mode optical fiber. The 10-Gb/s ON-OFF-keying signals can be independently transmitted and directly detected without coherent receiver and multiple-input multiple-output processing. Moreover, nonlinear transmission impairments are experimentally investigated.
Distributed optical fiber sensors (DOFSs) have faced the challenge of measuring transverse stress along the fiber and the current main approach has been based on polarization coupling effect in ...polarization-maintaining fibers (PMFs), which has short sensing length and high dependence on direction of exerted stress. Instead, here we propose a novel distributed transverse stress sensor (DTSS) based on coupling effect between linearly-polarized (LP) modes in weakly-coupled few-mode-fibers (FMFs). In this scheme, multiple LP modes could be considered as independent spatial channels without stress perturbation because of ultralow inherent modal crosstalk, while quantifiable and spatially-resolvable mode coupling for a probe signal will occur under transverse stress satisfying phase-matching conditions. A proof-of-concept DTSS system is verified based on weakly-coupled two-mode fibers and mode-selective couplers for mode conversion. Moreover, we show that the scheme is little affected by mild common parameters including temperature, strain, twist, direction of stress, or state-of-polarization (SOP), which is crucial for accurate stress analysis under complex environmental conditions. The proposed DTSS scheme has simple structure, high flexibility for different sensing ranges and resolutions, and high collaborating capability with other sensing mechanisms.
Glucosylsucroses are potentially useful as additives in cosmetic and pharmaceutical formulations. Although enzymatic synthesis of glucosylsucroses is the most efficient method for their production, ...the key enzyme that produces them has remained unknown. Here, we report that glucosylsucrose synthase from (TeGSS) catalyzes the synthesis of glucosylsucrose using sucrose and UDP-glucose as substrates. These saccharides are homologous to glucosylsucroses produced by sp. PCC 7120 (referred to as protein alr1000). When the ratio of UDP-glucose to sucrose is relatively high, TeGSS from cyanobacteria can hydrolyze excess UDP-glucose to UDP and glucose, indicating that sucrose provides a feedback mechanism for the control of glucosylsucrose synthesis. In the present study, we solved the crystal structure of TeGSS bound to UDP and sucrose. Our structure shows that the catalytic site contains a circular region that may allow glucosylsucroses with a right-hand helical structure to enter the catalytic site. Because active site residues Tyr18 and Arg179 are proximal to UDP and sucrose, we mutate these residues (., Y18F and R179A) and show that they exhibit very low activity, supporting their role as catalytic groups. Overall, our study provides insight into the catalytic mechanism of TeGSS.
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