Targeting the JAK2/STAT3 signaling pathway with natural plants and phytochemical ingredients: A novel therapeutic method for combatting cardiovascular diseases.

The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.

Thermal stratification and mixing processes response to meteorological factors in a monomictic reservoir.

Formation and extinction of thermal stratifications impact the reservoir ecosystems and have been closely influenced by meteorological and hydrological factors. However, quantifying the relative importance of these crucial environmental factors and mechanisms in reservoir regions characterized by various depths remain comparatively uninvestigated. Tianbao Reservoir is a typical monomictic warm and drinking water source reservoir in Southwest China. This study supplemented field observations with a three-dimensional numerical simulation model to quantitatively analyze mixing and turnover events. Air temperature and wind were two important meteorological factors resulting in hydrodynamics during stratification and mixing processes. Air temperature led to variations in stratification strength and wind-induced fluctuations of thermocline depth. A 10% rise in air temperature increased stratification strength by 18%, and a 3 m/s rise in wind speed induced the deepening of the thermocline by 2.09 m. Two hydrodynamics involved penetrative convection caused by temperature plummets and wind-induced mixing during winter turnover events were identified. Penetrative convection was the main driving force, and wind shear mixed the upper 21% of the mixed layer, which was contributed by convection. Response of water temperature to air temperature in shallow regions was faster (58 d), and the mixing depth caused by the wind was smaller than that in deep regions. Research on physical processes during stratification and mixing processes can provide support for further study on water quality deterioration distributions.

Genome-Wide Bioinformatics Analysis of SWEET Gene Family and Expression Verification of Candidate PaSWEET Genes in Potentilla anserina.

Sugars act as the main energy sources in many fruit and vegetable crops. The biosynthesis and transportation of sugars are crucial and especially contribute to growth and development. SWEET is an important gene family that plays a vital role in plants' growth, development, and adaptation to various types of stresses (biotic and abiotic). Although SWEET genes have been identified in numerous plant species, there is no information on SWEETs in Potentilla anserina. In the present study, we performed a comprehensive genome-wide bioinformatics analysis and identified a total of 23 candidate PaSWEETs genes in the Potentilla anserina genome, which were randomly distributed on ten different chromosomes. The phylogenetic analysis, chromosomal location, gene structure, specific cis-elements, protein interaction network, and physiological characteristics of these genes were systematically examined. The identified results of the phylogenetic relationship with Arabidopsis thaliana revealed that these PaSWEET genes were divided into four clades (I, II, III, and IV). Moreover, tissue-specific gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) validation exposed that the identified PaSWEETs were differentially expressed in various tissues (roots, stems, leaves, and flowers). Mainly, the relative fold gene expression in swollen and unswollen tubers effectively revealed that PaSWEETs (7, 9, and 12) were highly expressed (300-, 120-, and 100-fold) in swollen tubers. To further elucidate the function of PaSWEETs (7, 9, and 12), their subcellular location was confirmed by inserting them into tobacco leaves, and it was noted that these genes were present on the cell membrane. On the basis of the overall results, it is suggested that PaSWEETs (7, 9, and 12) are the candidate genes involved in swollen tuber formation in P. anserina. In crux, we speculated that our study provides a valuable theoretical base for further in-depth function analysis of the PaSWEET gene family and their role in tuber development and further enhancing the molecular breeding of Potentilla anserina.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

Co-application of concentrated biogas slurry and pyroligneous liquor mitigates ammonia emission and sustainably releases ammonium from paddy soil.

Biogas production causes vast amounts of biogas slurry (BS). Application of BS to croplands can substitute chemical fertilizers while result in higher ammonia emissions. Tremendous variation of ammonium concentration in different BSs induces imprecise substitution, while concentrated BS holds higher and more stable ammonium. Pyroligneous liquor, an acidic aqueous liquid from biochar production, can be used with concentrated BS to reduce ammonia emission. However, the effects of combining concentrated BS with pyroligneous liquor on ammonia emission and soil (nitrogen) N transformation have been poorly reported. In this study, a field experiment applying concentrated BS only, or combining with 5 %, 10 %, and 20 % pyroligneous liquor (v/v) for substituting 60 % N of single rice cultivation was conducted by contrast with chemical fertilization. The results showed that substituting chemical N fertilizers with concentrated BS increased 24.6 % ammonia emission. In comparison, applying 5 %, 10 %, and 20 % pyroligneous liquor with concentrated BS reduced 4.9 %, 20.3 %, and 24.4 % ammonia emissions, respectively. Applying concentrated BS with more pyroligneous liquor preserved higher ammonium and dissolved organic carbon in floodwater, and induced higher nitrate concentration after fertilization. Whereas soil ammonium and nitrate contents were decreased along with more pyroligneous liquor application before and after the topdressing and exhibited sustainable release until rice harvest. In comparison, the soil N mineralization and nitrification rates were occasionally elevated, while the activities of soil urease, protease, nitrate reductase, and nitrite reductase had multiple responses. Applying concentrated BS only, or combining with 5 %, 10, and 20 % pyroligneous liquor, have little effect on soil basic properties but inorganic N. In summary, applying concentrated BS with >10 % pyroligneous liquor could preserve more N with sustainable release and potentially lower N loss to the atmosphere, and we proposed that applying 13.5 % pyroligneous liquor in concentrated BS could achieve maximum soil fertility and minimum ammonia emission.

The Gß-like protein Bcgbl1 regulates development and pathogenicity of the gray mold Botrytis cinerea via modulating two MAP kinase signaling pathways.

The fungal Gß-like protein has been reported to be involved in a variety of biological processes, such as mycelial growth, differentiation, conidiation, stress responses and infection. However, molecular mechanisms of the Gß-like protein in regulating fungal development and pathogenicity are largely unknown. Here, we show that the Gß-like protein gene Bcgbl1 in the gray mold fungus Botrytis cinerea plays a pivotal role in development and pathogenicity by regulating the mitogen-activated protein (MAP) kinases signaling pathways. The Bcgbl1 deletion mutants were defective in mycelial growth, sclerotial formation, conidiation, macroconidial morphogenesis, plant adhesion, and formation of infection cushions and appressorium-like structures, resulting in a complete loss of pathogenicity. Bcgbl1 interacted with BcSte50, the adapter protein of the cascade of MAP kinase (MAPK). Bcgbl1 mutants had reduced phosphorylation levels of two MAPKs, namely Bmp1 and Bmp3, thereby reducing infection. However, deletion of Bcgbl1 did not affect the intracellular cAMP level, and exogenous cAMP could not restore the defects. Moreover, Bcgbl1 mutants exhibited defects in cell wall integrity and oxidative stress tolerance. Transcriptional profiling revealed that Bcgbl1 plays a global role in regulation of gene expression upon hydrophobic surface induction. We further uncovered that three target genes encoding the hydrophobic surface binding proteins (HsbAs) contributed to the adhesion and virulence of B. cinerea. Overall, these findings suggest that Bcgbl1 had multiple functions and provided new insights for deciphering the Bcgbl1-mediated network for regulating development and pathogenicity of B. cinerea.

Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.

PURPOSE: To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS: TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION: The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

Impact of Eucalyptus residue leaching on iron distribution in reservoir sediments assessed by high-resolution DGT technique.

Blackwater occurs every winter in reservoirs with Eucalyptus plantations. The complexation reaction between ferric iron (Fe3+) and Eucalyptus leachate tannic acid from logging residues (especially leaves) is the vital cause of water blackness. However, the effect of Eucalyptus leaf leaching on the dynamic of iron in sediments and its contribution to reservoir blackwater remain unclear. In this study, two experiments were conducted to simulate the early decomposition processes of exotic Eucalyptus and native Pinus massoniana leaves in water (LW) and water-sediment (LWS) systems. In LW, high concentrations of tannic acid (>45.25 mg/L) rapidly leached from the Eucalyptus leaves to the water column, exceeding those of Pinus massoniana leaves (<1.80 mg/L). The chrominance increased from 5~10 to 80~140, and the water body finally appeared brown instead of black after the leaching of Eucalyptus leaves. The chrominance positively correlated with tannic acid concentrations (R=0.970, p<0.01), indicating that tannic acid was vital for the water column's brown color. Different in LWS, blackwater initially emerged near the sediment-water interface (SWI) and extended upward to the entire water column as Eucalyptus leaves leached. Dissolved oxygen (DO) and transmission values in the overlying water declined simultaneously (R>0.77, p<0.05) and were finally below 2.29 mg/L and 10%, respectively. During the leaching of Eucalyptus leaves, the DGT-labile Fe2+ in sediments migrated from deep to surface layers, and the diffusive fluxes of Fe2+ at the SWI increased from 12.42~19.93 to 18.98~26.28 mg/(m2·day), suggesting that sediment released abundant Fe3+ into the aerobic overlying water. Fe3+ was exposed to high concentrations of tannic acid at the SWI and immediately generated the black Fe-tannic acid complex. The results indicated that the supplement of dissolved Fe3+ from sediments is a critical factor for the periodic blackwater in the reservoirs with Eucalyptus plantations. Reducing the cultivation of Eucalyptus in the reservoir catchment is one of the effective ways to alleviate the reservoir blackwater.

Soil acidification and salinity: the importance of biochar application to agricultural soils.

Soil acidity is a serious problem in agricultural lands as it directly affects the soil, crop production, and human health. Soil acidification in agricultural lands occurs due to the release of protons (H+) from the transforming reactions of various carbon, nitrogen, and sulfur-containing compounds. The use of biochar (BC) has emerged as an excellent tool to manage soil acidity owing to its alkaline nature and its appreciable ability to improve the soil's physical, chemical, and biological properties. The application of BC to acidic soils improves soil pH, soil organic matter (SOM), cation exchange capacity (CEC), nutrient uptake, microbial activity and diversity, and enzyme activities which mitigate the adverse impacts of acidity on plants. Further, BC application also reduce the concentration of H+ and Al3+ ions and other toxic metals which mitigate the soil acidity and supports plant growth. Similarly, soil salinity (SS) is also a serious concern across the globe and it has a direct impact on global production and food security. Due to its appreciable liming potential BC is also an important amendment to mitigate the adverse impacts of SS. The addition of BC to saline soils improves nutrient homeostasis, nutrient uptake, SOM, CEC, soil microbial activity, enzymatic activity, and water uptake and reduces the accumulation of toxic ions sodium (Na+ and chloride (Cl-). All these BC-mediated changes support plant growth by improving antioxidant activity, photosynthesis efficiency, stomata working, and decrease oxidative damage in plants. Thus, in the present review, we discussed the various mechanisms through which BC improves the soil properties and microbial and enzymatic activities to counter acidity and salinity problems. The present review will increase the existing knowledge about the role of BC to mitigate soil acidity and salinity problems. This will also provide new suggestions to readers on how this knowledge can be used to ameliorate acidic and saline soils.

How Does Zinc Improve Salinity Tolerance? Mechanisms and Future Prospects.

Salinity stress (SS) is a serious abiotic stress and a major constraint to agricultural productivity across the globe. High SS negatively affects plant growth and yield by altering soil physio-chemical properties and plant physiological, biochemical, and molecular processes. The application of micronutrients is considered an important practice to mitigate the adverse effects of SS. Zinc (Zn) is an important nutrient that plays an imperative role in plant growth, and it could also help alleviate the effects of salt stress. Zn application improves seed germination, seedling growth, water uptake, plant water relations, nutrient uptake, and nutrient homeostasis, therefore improving plant performance and saline conditions. Zn application also protects the photosynthetic apparatus from salinity-induced oxidative stress and improves stomata movement, chlorophyll synthesis, carbon fixation, and osmolytes and hormone accumulation. Moreover, Zn application also increases the synthesis of secondary metabolites and the expression of stress responsive genes and stimulates antioxidant activities to counter the toxic effects of salt stress. Therefore, to better understand the role of Zn in plants under SS, we have discussed the various mechanisms by which Zn induces salinity tolerance in plants. We have also identified diverse research gaps that must be filled in future research programs. The present review article will fill the knowledge gaps on the role of Zn in mitigating salinity stress. This review will also help readers to learn more about the role of Zn and will provide new suggestions on how this knowledge can be used to develop salt tolerance in plants by using Zn.

A comprehensive method for causation analysis of ship-ice collision risk in Arctic waters.

The influence of harsh Arctic environmental factors has caused ship-ice collision accidents to become the main threat faced by navigating ships. It is necessary to quantify the causation of ship accidents and perform effective risk management and control measures to ensure ship navigation safety. This study proposes a Bayesian network (BN) model-based risk analysis method for ship-ice collision accidents, which is used to quantitatively analyze the key risk factors and primary risk causation paths of ship accidents. First, the fault tree analysis (FTA) method is proposed to constructing the BN structure model, and the BN parameter solution method is further established. Consequently, a triangular fuzzy and defuzzification method is developed to quantify uncertain expert knowledge. Then, the BN inference method is used to analyze the collision risk causation where the North Atlantic and Arctic waters meet. The results indicate that the main risk factors in Arctic waters come from the environment. There are four primary risk causation paths; the proposed management and control measures of the risk causation paths (A), (B), (C), and (D) can effectively reduce the navigation risk by 29.95%, 9.98%, 25.05%, and 3.99%, respectively; the combination of these four measures can reduce the navigation risk by 54.63%.The proposed method has positive guiding significance for ensuring the safety of ship navigation in Arctic waters.

M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch.

Early-life immune development is critical to long-term host health. However, the mechanisms that determine the pace of postnatal immune maturation are not fully resolved. Here, we analyzed mononuclear phagocytes (MNPs) in small intestinal Peyer's patches (PPs), the primary inductive site of intestinal immunity. Conventional type 1 and 2 dendritic cells (cDC1 and cDC2) and RORgt+ antigen-presenting cells (RORgt+ APC) exhibited significant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, subsequently resulting in a lack in CD4+ T cell priming during the postnatal period. Microbial cues contributed but could not fully explain the discrepancies in MNP maturation. Type I interferon (IFN) accelerated MNP maturation but IFN signaling did not represent the physiological stimulus. Instead, follicle-associated epithelium (FAE) M cell differentiation was required and sufficient to drive postweaning PP MNP maturation. Together, our results highlight the role of FAE M cell differentiation and MNP maturation in postnatal immune development.

Artificial humic acid regulates the impact of fungal community on soil macroaggregates formation.

Artificial humic acid (A-HA), which is synthesized from agricultural wastes and has high similarity to a natural humic substance (HS) extracted from soil, has been proven by our group to have potential for biological carbon sequestration in black soils. However, the mechanism involves in the application of A-HA on soil aggregation processes resulting from microbial activity stimulation and modifications to microbial communities remains unclear. This study investigates the correlation between the formation and stability of soil aggregates and fungal communities with various amounts of A-HA added to the rhizosphere and non-rhizosphere soil. A-HA can increase the total organic carbon (TOC) and dissolved organic carbon (DOC) concentrations in soil, promoting macroaggregate formation and increasing the mean weight diameter (MWD). In addition, soil aggregate binding agents such as polysaccharides, protein, extracellular polymeric substances (EPS), and glomalin-related soil protein (GRSP) are significantly increased by the addition of A-HA. A-HA can drive microaggregate to assemble into macroaggregate by increasing the abundance of beneficial fungi (e.g., Trichoderma and Mortierella). The co-occurrence network supports that A-HA shifted the key species and increased interactions of fungal taxa. This study will lay a solid foundation for sustainable agricultural development of A-HA application for soil fertility restoration in the future.

MiR-92a expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening.

OBJECTIVE: This study seeks to assess the efficacy of exfoliated colonocytes isolated from feces (ECIF) miR-92a as a clinical colorectal cancer diagnostic marker in a larger cohort. METHODS: Clinicopathologic data from colorectal cancer patients and health controls that underwent colonoscopy, as well as patients of other cancers diagnosed, were included. A total of 963 Chinese participants were enrolled, with 292 (27.4%) having colorectal cancer, 140 (14.5%) having other types of cancer, e.g., pancreatic, liver, oral, bile duct, esophagus, and stomach cancer, 171 (17.8%) having infection in the intestine, rectal, stomach, appendix, and gastrointestinal ulcer, and 360 (37.4%) of healthy controls. ECIF samples were gathered and miR-92a levels were detected using TaqMan probe-based miR-92a real-time quantitative PCR (RT-qPCR) kit developed by Shenzhen GeneBioHealth Co., Ltd. RESULTS: Through a series of experiments, we demonstrated that the Ep-LMB/Vi-LMB magnetic separation system is feasible, highly specific, and highly sensitive at a cutoff value of 1053 copies per 6 ng of ECIF RNA. ECIF miR-92a levels were significantly higher in colorectal cancer patients than in controls. Colorectal cancer detection sensitivity and specificity were 87.3% and 86.9% respectively. Furthermore, the performance of this miR-92a detection kit demonstrated that it is an effective tool for colorectal cancer, with a high sensitivity of 84.1%, even in early cancer stages (0, I, and II). Furthermore, tumor removal resulted in lower stool miR-92a levels (3.21±0.58 vs. 2.14±1.14, P < 0.0001, n = 65). CONCLUSION: Finally, the miR-92a RT-qPCR kit detects ECIF-increased miR-92a and could be used for colorectal cancer screening.

Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia.

Background: Chronic intermittent hypoxia (CIH) could cause neuronal damage, accelerating the progression of dementia. However, safe and effective therapeutic drugs and delivery are needed for successful CIH therapy. Purpose: To investigate the neuroprotective effect of Huperzine A (HuA) packaged with nanoliposomes (HuA-LIP) on neuronal damage induced by CIH. Methods: The stability and release of HuA-LIP in vitro were identified. Mice were randomly divided into the Control, CIH, HuA-LIP, and HuA groups. The mice in the HuA and HuA-LIP groups received HuA (0.1 mg/kg, i.p.), and HuA-LIP was administered during CIH exposure for 21 days. HuA-LIP contains the equivalent content of HuA. Results: We prepared a novel formulation of HuA-LIP that had good stability and controlled release. First, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice. Second, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH. Furthermore, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression. In addition, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity. Most importantly, compared with HuA, HuA-LIP showed a superior performance against neuronal damage induced by CIH. Conclusion: HuA-LIP has a good sustained-release effect and targeting ability and efficiently protects against neural injury caused by CIH.

Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy.

Breast-conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self-assembled multifunctional nanoprobe (NP) gadolinium (Gd)-diethylenetriaminepentaacetic acid-human serum albumin (HSA)@indocyanine green-Bevacizumab (NPs-Bev) is synthesized to improve the efficacy of fluorescence-image-guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor-bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X-ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self-assembled NPs-Bev using HSA, the magnetic resonance contrast agent and Bevacizumab-targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self-assembled NPs provide a solid precision therapy platform to treat breast cancer.

The on-off-on Fluorescence Sensor of Hollow Carbon Dots for Detecting Hg2+ and Ascorbic Acid.

Carbon dots (CDs) have excellent fluorescence properties and can be used in many research fields. In this paper, carbon dots were prepared by microwave-assisted pyrolysis of citric acid and urea, characterized by transmission electron microscope (TEM), X-ray diffractometer (XRD), 13C-NMR spectrum, zeta potential, Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-vis) absorption and fluorescence spectra, and detected the Hg2+ and ascorbic acid (AA) sequentially. It showed that carbon dots were hollow, spherical particles and less than 10 nm, photoluminescence quantum yield of carbon dots was about 15%. The CDs were selective and sensitive to Hg2+ and AA based on the "on-off-on" fluorescence behavior. The detection limits of CDs for Hg2+ and AA were 0.138 µM and 0.212 µM, respectively. Fluorescence response mechanism of CDs was also discussed.

N-doped carbon dots as the multifunctional fluorescent probe for mercury ion, glutathione and pH detection.

Recently, carbon dots (CDs) have exhibited promising applications in the fluorescence detection of various ions and biomolecules. In this work, one kind of nitrogen-doped CDs (N-CDs) with high fluorescence intensity was synthesized, characterized by transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, Fourier-transform infrared, UV-vis absorption spectra, and fluorescence spectra. The results show that the spherical and uniform N-CDs (quantum yield: 60.2%) have remarkable fluorescence properties and photostability, which makes N-CDs can be utilized as an 'on-off-on' sensor for Hg2+and glutathione (GSH). In addition, the pH-sensitive behavior of N-CDs makes it also applicable to H+detection under acid conditions (pKa = 3.53). The linear range of the 'turn-off' sensor detecting Hg2+was 0.014-50µM, with a 0.014µM limit of detection (LOD). GSH was detected by the fluorescence 'turn-on' method with a linear range of 0.125-60µM and a LOD of 0.125µM. The outstanding performance of N-CDs makes it potential applications in ecological pollution and biomolecule visualization monitoring.

A dynamic reversible phenylboronic acid sensor for real-time determination of protein-carbohydrate interactions on living cancer cells.

Real-time detection of glycosylation on label-free cancer cell surfaces is of significance for the diagnosis and treatment of cancer. In this work, we have successfully developed a novel dynamic reversible sensor based on pH-sensitive phenylboronic esters to determine in real-time the binding kinetics of protein-carbohydrate interactions on suspension cancer cell surfaces using a quartz crystal microbalance (QCM) technique.

Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes.

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide with critical roles in the development of peripheral sensitization and pain. One of the CGRP family peptides, islet amyloid polypeptide (IAPP), is an important autoantigen in type 1 diabetes. Due to the high structural and chemical similarity between CGRP and IAPP, we expected that the CGRP peptide could be recognized by IAPP-specific CD4 T cells. However, there was no cross-reactivity between the CGRP peptide and the diabetogenic IAPP-reactive T cells. A set of CGRP-specific CD4 T cells was isolated from non-obese diabetic (NOD) mice. The T-cell receptor (TCR) variable regions of both α and ß chains were highly skewed towards TRAV13 and TRBV13, respectively. The clonal expansion of T cells suggested that the presence of activated T cells responded to CGRP stimulation. None of the CGRP-specific CD4 T cells were able to be activated by the IAPP peptide. This established that CGRP-reactive CD4 T cells are a unique type of autoantigen-specific T cells in NOD mice. Using IAg7-CGRP tetramers, we found that CGRP-specific T cells were present in the pancreas of both prediabetic and diabetic NOD mice. The percentages of CGRP-reactive T cells in the pancreas of NOD mice were correlated to the diabetic progression. We showed that the human CGRP peptide presented by IAg7 elicited strong CGRP-specific T-cell responses. These findings suggested that CGRP is a potential autoantigen for CD4 T cells in NOD mice and probably in humans. The CGRP-specific CD4 T cells could be a unique marker for type 1 diabetes. Given the ubiquity of CGRP in nervous systems, it could potentially play an important role in diabetic neuropathy.