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The formation of microbial biofilms is acknowledged as a major virulence factor in a range of persistent local infections. Failures to remove biofilms with antibiotics foster the emergence of antibiotic-resistant bacteria and result in chronic infections. As a result, the construction of effective biofilm-inhibiting and biofilm-eradicating chemicals is urgently required. Herein, we designed a water-soluble probe

Polygonatum sibiricum polysaccharides (PSPs) have the function of nourishing the nerves and beneficial intelligence, but the underlying mechanisms remain unclear. Here we initially isolated and purified a monomeric polysaccharide named PSP-1 from PSPs. UV and IR were utilized for characterizing PSP-1. The molecular weight of PSP-1 was 18.796 kDa. Utilizing 5xFAD mice as a research model, we identified that the initial time of PSP-1 oral administration was 3 months of age for mice by determining the 16S rRNA of fecal samples from wild type (WT) and 5xFAD mice at 3 months or 6 months of age. A 3-month course of PSP-1 improved the pathological behaviors related to memory and cognition, prevented synaptic loss, enhanced microglial phagocytosis of Aβ plaques, and decreased the concentrations of Aβ1-40 and Aβ1-42 in the brains of 5xFAD mice. Moreover, PSP-1 reconstructed the gut microbiota composition, including reducing the relative abundance of Helicobacter, and increasing Akkermansia muciniphila. The gut barrier integrity damage, the inflammatory responses, and the intestinal Aβ deposition were prevented by the PSP-1 treatment. The present study identified a monomeric polysaccharide purified from PSPs that significantly attenuates the cognitive deficits in 5xFAD mice, which could be partly explained by the reshaped gut microbiome.

Excessive mercury ions (Hg2+) in the environment can accumulate in human body along with the food chain to cause serious physiological reactions. The fluorescence probes were considered as convenient tool with great potential for Hg2+ detection. Most existing probes suffer from aggregation-induced quenching (ACQ) effects and insufficient sensitivity. Herein, a novel type of fluorophore was developed by combining the aggregation-induced emission (AIE) and excited state intramolecular proton transfer (ESIPT) characteristics. Subsequently, a phenyl thioformate group with photoinduced electron transfer (PET) effect was connected to give an efficient "turn-on" probe (HTM), which exhibited good selectivity toward Hg2+, short response time (30 min), coupled with extremely low detection limit (LOD = 1.68 nmol/L). In addition, HTM was used successfully in real samples, cells and drug evaluation, underlying the superiority of HTM to detect Hg2+ in practical applications.

The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression

Intracellular pH is a key parameter related to various biological and pathological processes. In this study, a ratiometric pH fluorescent sensor ABTT was developed harnessing the amino-type excited-state intramolecular proton transfer (ESIPT) process. Relying on whether the ESIPT proceeds normally or not, ABTT exhibited the yellow fluorescence in acidic media, or cyan fluorescence in basic condition. According to the variation, ABTT behaved as a promising sensor which possessed fast and reversible response to pH change without interference from the biological substances, and exported a steady ratiometric signal (I478/I546). Moreover, due to the ESIPT effect, large Stokes shift and high quantum yield were also exhibited in ABTT. Furthermore, ABTT was applied for monitoring the pH changes in living cells and visualizing the pH fluctuations under oxidative stress successfully. These results elucidated great potential of ABTT in understanding pH-dependent physiological and pathological processes.

As a potential oncogene, nucleolar and spindle‑associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. However, the role of NUSAP1 in non‑small cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the biological function and underlying molecular mechanisms of NUSAP1 in NSCLC. NUSAP1 expression was measured in NSCLC tissues and cell lines via immunohistochemistry and western blotting, respectively. NSCLC cell lines stably inhibiting NUSAP1 were established to investigate its effects on cell proliferation, colony formation and invasion, and on in vivo tumorigenicity. Additionally, the upstream and downstream mechanisms of NUSAP1 in regulating NSCLC progression were investigated. The results indicated that NUSAP1 expression was upregulated in NSCLC tissues and cell lines. High NUSAP1 expression was associated with tumor size, TNM stage, lymph node metastasis and poor patient survival, whereas knockdown of NUSAP1 inhibited NSCLC cell proliferation, colony formation and invasion. Furthermore, downregulation of NUSAP1 decreased the growth of NSCLC xenografts in vivo. In addition, myocyte enhancer factor 2D (MEF2D) directly targeted the NUSAP1 promoter, thereby enhancing the mRNA and protein expression levels of NUSAP1. Moreover, the results demonstrated that MEF2D expression was upregulated in NSCLC tissues and was positively correlated with NUSAP1 expression. MEF2D‑knockdown decreased NSCLC cell proliferation, colony formation and invasion. NUSAP1 upregulation reversed the effects of MEF2D‑knockdown on NSCLC progression. Furthermore, it was observed that MEF2D‑knockdown inhibited the accumulation and nuclear translocation of β‑catenin, thereby repressing the activation of the Wnt/β‑catenin signaling pathway in NSCLC cells, whereas NUSAP1 upregulation rescued the effects of MEF2D‑knockdown on the activation of the Wnt/β‑catenin signaling pathway. In conclusion, the findings of the present study indicated that the MEF2D/NUSAP1 signaling pathway promoted NSCLC progression by inducing the activation of Wnt/β‑catenin signaling, and this novel mechanism may represent a potential treatment target for patients with NSCLC.

Given that triple-negative breast cancer (TNBC) lacks specific receptors (estrogen and progesterone receptors and human epidermal growth factor receptor 2) and cannot be treated with endocrine therapy, chemotherapy has remained the mainstay of treatment. Drug resistance is reportedly the main obstacle to the clinical use of doxorubicin (DOX) in this patient population. Accordingly, screening molecules related to chemoresistance and studying their specific mechanisms has clinical significance for improving the efficacy of chemotherapy in TNBC patients. Thioredoxin-interacting protein (TXNIP) is a metabolism-related protein that plays a tumor suppressor role in various malignant tumors; however, the specific role of TXNIP in tumor chemoresistance has not been reported. In the present study, we explored the potential molecular mechanism of TXNIP in the chemoresistance of TNBC for the first time. The results showed that TXNIP inhibited the proliferation of TNBC drug-resistant cells and promoted apoptosis in vitro and in vivo. Furthermore, TXNIP promoted the synthesis of reactive oxygen species (ROS) and the accumulation of DNA damage caused by DOX and increased γ-H2AX levels in a time and dose-dependent manner. Moreover, ROS scavenger pretreatment could block DNA damage induced by TXNIP and restore the resistance of TNBC resistant cells to DOX to a certain extent. In addition, we found that the small molecule c-Myc inhibitor 10058-F4 promoted TXNIP expression, increased ROS synthesis in cells, and could enhance the cytotoxicity of chemotherapy drugs in vitro and in vivo when combined with DOX. These results indicated that c-Myc inhibitor 10058-F4 could induce TXNIP upregulation in TNBC drug-resistant cells, and the upregulated TXNIP increased the accumulation of ROS-dependent DNA damage, thereby decreasing chemotherapy resistance of TNBC. Our findings reveal a new mechanism of mediating drug resistance and provide a new drug combination strategy to overcome DOX resistance in TNBC.

Needles ofJuniperus rigidaare used in Chinese traditional medicine for the treatment of brucellosis, dropsy, skin disease, and rheumatoid arthritis. This is the first study that reports anatomical structures of theJ. rigidaneedles collected at different altitudes. The most common anatomical, phytochemical, and histochemical techniques and methods are used. The results show that anatomical structures and chemical composition change significantly at different altitudes. The main anatomical characters are significant xeromorphic structures (thick epidermis, hypodermis, and cuticle), a stomatal band, a developed vascular bundle, and a marginal resin duct. The xeromorphic structures become more pronounced with increasing altitude. The phytochemical and histochemical results demonstrate that the content of the main chemical compounds (phenols and terpenoids) basically increases at a higher elevation. Histochemical analysis localizes the phenols in epidermal cells, sponge tissue, endothelial layer cells, and stomatal bands, and the terpenoids in palisade tissue, sponge tissue, and the edge of the resin duct. This work reveals the relation between anatomy and chemistry inJ. rigidaneedles, contributes to the quality control of its ethno-medicine, and provides the evidence to develop the commercial cultivation.

Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E‐cad and Ki‐67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E‐cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P

In clinical diagnosis and treatment, it is very important to distinguish cancer cells from normal cells. Nuclear-selective fluorescent probe that specifically target tumors can not only make the difference in assessing tumor margins during surgery and then facilitating accurate resection of the tumor, but also can provide crucial biomedical information of tumor progress if it can be used for long-term dynamic visualization of nucleus in cancer. Herein, a novel fluorescent probe 3 was designed and characterized to be of low-toxicity and water-solubility. The biological evaluation indicated that probe 3 prefers nucleic acids rather than accumulation in non-neuclear sites while superior to the commercial available agent DAPI (4',6-diamidino-2-phenylindole), in terms of its character of aggregation-induced emission (AIE), large Stokes shift (175 nm) and light stability. Further experiments demonstrated that probe 3 can not only differentiate SW480 and SW620 (cancer cells) from GES-1 (normal cells) with high contrast (dyed in nuclear of cancer cells and not in nuclear of normal cells), but also used for tracking cancer cell nuclear for long time. Furthermore, 3D reconstruction fluorescence imaging proved that probe 3 was able for identifying colorectal cancer tissues from para-carcinoma tissues by a strong contrast. Therefore, in precise surgery of colorectal cancer, probe 3 may be a promising-agent for guiding of intraoperation.

Using Hg2+-induced umpolung reaction and aggregation induced emission (AIE), we have rationally developed a water-soluble fluorescent probe 2,2'-(((4-(4,5-bis(4-methoxyphenyl)-1-phenyl-1H-imidazol-2-yl)phenyl)methylene)bis(sulfanediyl))diethanol (MPIPBS) for Hg2+ detection. MPIPBS was found to have high selectivity and sensitivity toward Hg2+ detection. The mechanism of MPIPBS response to Hg2+ was verified by 1H NMR titration, HPLC, and HRMS spectroscopy. The detection limit was examined to be 1.45 nM, which is lower than most reported probes for Hg2+. Taking advantage of excellent optical properties of AIEgen, a paper based sensor for Hg2+ detection was fabricated by immobilizing the MPIPBS on Waterman test paper. Meanwhile, MPIPBS showed satisfactory analytical performance in real water and urine samples. Further, thanks to the high water solubility, cell membrane permeability and low cytotoxicity, MPIPBS was further used to detect Hg2+ both in living cells and zebrafish. We anticipate that the prepared probe was available to detect Hg2+ in environment and biosamples.

γ-Glutamyl transpeptidase (GGT) has been reported as a biomarker of hepatocellular carcinoma (HCC), and its imaging is of great benefit for early detection in precise medicine as well as intraoperative navigation. Herein, we have designed and synthesized a novel near-infrared fluorescent probe coupled aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) effect for the detection of GGT. Thanks to conjugated glutamate acid, this probe could be dispersed in aqueous solution and showed barely any fluorescence emission. Through a GGT-mediated enzymatic reaction, the aggregation state of the probe in aqueous solution was changed and an intramolecular hydrogen bond was formed, resulting in an enhanced fluorescence emission. An excellent linear relationship was observed and the concentration of GGT measured was in the range of 10-90 U L-1 with a limit of detection calculated at 2.9 U L-1. Its feasibility has been confirmed by detecting GGT in HepG2 cells with high specificity and long-term sustainability, satisfying clinical need. Moreover, this nanoprobe showed great potential for precise medicine guided surgery by realizing fluorescence imaging in human liver tumour tissue and distinguishing it from normal tissue. Thus, we supposed that our AIE coupled ESIPT fluorescent nanoprobe has great potential in the early detection of HCC, the selective fluorescence imaging of GGT positive cells during surgery and application in precision medicine.

Background Tumor resistance to radiotherapy is one of the main obstacles to the clinical treatment of nasopharyngeal carcinoma (NPC). Improving the radiosensitivity of tumor cells has an important clinical significance in treatment of clinical NPC. This study aimed to identify that miR-138-1-3p as a novel therapeutic target in radioresistant NPC cells and found its targets, CRIPTO and the JAK2/STAT3 pathway. Methods Radioresistant C666-IR and HK-1R cells were derived from the NPC cell lines C666-1 and HK-1. The different microRNAs (miRNAs) and their targeting genes were analyzed between C666-1 and C666-IR cells using microarray bioinformatics. Western blot, qRT-PCR, gene transfection, Luciferase reporter assay, and confocal laser scanning microscopy were applied for the analysis of the different genes. Results MiR-138-1-3p was found to target CRIPTO, which involved in the epithelial-mesenchymal transition (EMT) and JAK2/STAT3 signaling pathways. The luciferase reporter assay confirmed that miR-138-1-3p targeted CRIPTO and downregulated the expression of CRIPTO. Furthermore, miR-138-1-3p affected the stability of the CRIPTO-GRP78 complex on the cell membrane and also reversed the radioresistant characteristics of NPC stem cells, which affected EMT and the JAK2/STAT3 signaling pathway. Conclusions The miR-138-1-3p is a small molecule that can modulate radiosensitivity in the radioresistant C666-IR and HK-1R NPC cell lines by inhibiting EMT and targeting CRIPTO to reduce the activation of the JAK2/STAT3 pathway.

Due to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC.

Overexpression of ANXA1 and EphA2 has been linked to various cancers and both proteins have attracted considerable attention for the development of new anticancer drugs. Here we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination and degradation in nasopharyngeal carcinoma (NPC). Binding of ANXA1 to EphA2 promoted NPC cell growth and metastasis in vitro and in vivo by elevating EphA2 levels and increasing activity of EphA2 oncogenic signaling (pS897-EphA2). Expression of ANXA1 and EphA2 was positively correlated and both were significantly higher in NPC tissues than in the normal nasopharyngeal epithelial tissues. Patients with high expression of both proteins presented poorer disease-free survival and overall survival relative to patients with high expression of one protein alone. Furthermore, amino acid residues 20-30aa and 28-30aa of the ANXA1 N-terminus bound EphA2. An 11 amino acid–long ANXA1-derived peptide (EYVQTVKSSKG) was developed on the basis of this N-terminal region, which disrupted the connection of ANXA1 with EphA2, successfully downregulating EphA2 expression and dramatically suppressing NPC cell oncogenicity in vitro and in mice. These findings suggest that ANXA1 promotes NPC growth and metastasis via binding and stabilization of EphA2 and present a strategy for targeting EphA2 degradation and treating NPC with a peptide. This therapeutic strategy may also be extended to other cancers with high expression of both proteins. Significance: These findings show that EphA2 is a potential target for NPC therapeutics and an ANXA1-derived peptide suppresses NPC growth and metastasis.

Glucose-regulated protein 78 (GRP78) was revealed to be associated with the radioresistance of nasopharyngeal carcinoma (NPC) in our previous study. GRP78 is a highly expressed cell surface protein, and holds great promise as a cancer specific target. Its expression may be impacted by the regulation of miRNAs, which may be involved in the radioresistance of NPC. A better understanding of the mechanisms of radioresistance may generate new targets of therapy for NPC patients. The present study was designed to investigate the effect of microRNA targeting GRP78 on the radiosensitivity of NPC. First, we used miRWalk software to predict miRNAs that may interact with GRP78. Subsequently, analysis of miR-495 and GRP78 expression was performed in the primary tissues of 92 NPC tissues and cell lines by immunohistochemistry and real-time PCR and the results revealed that miR-495 expression was lower in radioresistant NPC tissues in comparison to chronic rhinitis tissues, and also lower in radioresistant 5-8F cells (5-8F-IR) in comparison to its parental 5-8F cells. Notably, we observed an inverse association between the expression miR-495 and GRP78. Our bioinformatics analysis led to the identification of miR-495 as the optimal miRNA interacting with GRP78 mRNA. Furthermore, miR-495 targeting the 3′untranslated region (UTR) of GRP78 was detected by a Dual-Glo Luciferase Assay system. Finally, we observed that miR-495 inhibition led to a significant increase in the radioresistance of 5-8F cells and higher GRP78 expression, which may be involved in epithelial-mesenchymal transition (EMT) phenotype. miR-495 targeted the 3′UTR of GRP78 and contributed to the efficacy of radiation therapy in NPC.

Water-holding capacity is closely related to gel microstructure, and is a very important quality trait in surimi and surimi product. The changes in the secondary structure, gel microstructure, and the migration of water in bighead carp (Aristichthys nobilis) myosin gel induced by different temperatures (50–90°C) were investigated. The α-helical structure of myosin decreased at temperatures of 40°C or higher. The fractal dimension of the gels increased at 40, 50, and 60°C, but decreased at temperatures over 60°C. The pore size of the gels increased with temperatures up to 50°C, decreased at 60°C, and then increased with temperatures up to 90°C again. The transverse relaxation times also varied; T21 remained constant at temperatures over 40°C; T22 decreased at temperatures lower than 50°C, increased at 60°C, and then decreased with temperatures up to 90°C; and T23 increased at temperatures lower than 50°C and then remained constant until 90°C. Principal component analysis showed that the proportion of T22 water (PT22) was inversely correlated with the unfolding of myosin, whereas directly correlated with the pore size. The proportion of T23 water (PT23) was positively correlated with the fractal dimensions of the gels, whereas negatively correlated with the pore size. The migration of the secondary layer of water was mainly caused by hydrophobic force and the physical space formed by the myosin backbone, and the migration of water within the third layer was mainly caused by capillary pressure. Therefore, the mobility and redistribution of waters depend on the water retention mechanism, which is determined by the physical structure of gels. This study provides further information about the relationship between the NMR data, gel microstructure, water mobility, and distribution.

Herein, a novel self-assembled nanoprobe for the long-term tracking of the nucleoli of cancer cells and for differentiating between clinical breast cancer tissues and para-carcinoma tissues has been developed.

Carbon monoxide (CO) is an important gasotransmitter to regulate various physiological processes. Visualization of CO in situ would be conducive to uncover its physiological/pathological role. Unfortunately, most current CO fluorescent probes display aggregation-caused quenching (ACQ) characters. Herein, we reported a new fluorophore (MTPIM-HBT) coupling with aggregation-induced emission (AIE), excited-state intramolecular proton transfer (ESIPT), and intramolecular charge transfer (ICT) characteristics by attaching 2-(2′-hydroxyphenyl)benzothiazole (HBT) on methoxyl-substituted tetraarylimidazole derivative. Because of the synergistic effects, this fluorophore presented an all-purpose platform for developing ratiometric fluorescent probes with promising optimized properties. Hence, two reaction-based fluorescent probes (MTIPIM-AF-CO and MTPIM-AE-CO) for ratiometric detection and imaging of CO were rationally designed based on these unique scaffolds via one-step facilely synthesis. These probes have the merits of superior selectivity and excellent sensitivity with detection limit 47.5 nM and 32.2 nM, respectively. Significantly, the practicability of probes for visual detection of CO in air and ratiometric detection of exogenous and endogenous CO in living cells were successfully elucidated as well.

The α-helix of myosin decreased and the diameter of the myosin clusters increased monotonically with increasing heating time at 50 and 90°C. The clusters that formed during heating at 90°C were much larger than those that formed at 50°C. With increasing heating time, the G′ of the myosin heated at 50°C increased, but it decreased in the myosin heated at 90°C. The rheology data suggested that myosin heated at 50°C exhibited better gel formation than myosin that was heated at 90°C. The myosin gel network formed at 50°C was more consistent and homogeneous, whereas the gel formed 90°C was irregular and sturdy. Myosin heated at 50°C tended to form small, open clusters via heads, and the tails were outstretched, whereas the clusters that formed via myosin heads and tails at 90°C were larger and closed. Al aplicar un tratamiento de calentamiento a temperaturas de 50 °C y 90 °C se constató que, a medida que aumentó la duración del calentamiento, se redujo la hélice-α de miosina y se incrementó monotónicamente el diámetro de los clústeres de miosina. Los clústeres que se produjeron durante el calentamiento a 90 °C fueron más largos que los formados en el calentamiento a 50 °C. A medida que se incrementó la duración del tratamiento térmico aumentó la G’ de la miosina sometida a calentamiento a 50 °C, disminuyendo cuando la miosina fue calentada a 90 °C. Los datos reológicos sugieren que la miosina calentada a 50 °C produjo una mejor formación de gel que aquella que se calentó a 90 °C. Además, la red de gel de miosina formada a 50 °C fue más consistente y homogénea, evidenciándose que el gel formado a 90 °C era irregular y macizo. La miosina sometida a calentamiento a 50 °C tendió a formar clústeres pequeños y abiertos en las cabezas y las colas se presentaron alargadas, en tanto los clústeres formados mediante cabezas y colas de miosina calentada a 90 °C fueron más grandes y cerrados.

Anionic surfactants are widely used in detergents, cosmetics, medicine and other industries, but the residue in the water can pollute the water quality and destruct aquatic ecosystems. Thus, to develop a rapid, sensitive and selective strategy for detection of anionic surfactants is of great importance. Herein, we rationally designed and synthesized a novel fluorescent dye TPIM-ClO4 with excellent characters based on aggregation-induced emission (AIE). TPIM-ClO4 exhibited many incomparable characteristics including large Stokes shifts (225 nm), long wavelength emission (650 nm), excellent water solubility and stability. It was demonstrated to be excellent probe for detection of sodium dodecyl sulfate with fast-responding (40 s), good selectivity and extremely low detection limit 48 nM (13.07 μg/L), which ascribe to the formation of tightly packed nanoaggregates in situ based on synergistic electrostatic and hydrophobic interactions. TPIM-ClO4 was further successfully used to the detection of sodium dodecyl sulfate in real water samples with satisfactory results. Furthermore, probe TPIM-ClO4 was also successfully applied for specific fluorescent imaging of Gram-positive bacteria without washing steps. This study may provide new strategy in designing AIE-based fluorescent probe for environmental monitoring and microbial analysis application.

A novel fluorescent probe HPQB based on ESIPT and AIE was developed for the detection of H2O2 and glucose. HPQB was found with large Stokes shift (167 nm) characters. Probe HPQB exhibited high selectivity and excellent sensitivity for H2O2 and glucose. Moreover, HPQB was also employed as a fluorescent probe for imaging H2O2 in nasopharyngeal carcinoma (NPC) cells.

Needles of Juniperus rigida are used in Chinese traditional medicine for the treatment of brucellosis, dropsy, skin disease, and rheumatoid arthritis. This is the first study that reports anatomical structures of the J. rigida needles collected at different altitudes. The most common anatomical, phytochemical, and histochemical techniques and methods are used. The results show that anatomical structures and chemical composition change significantly at different altitudes. The main anatomical characters are significant xeromorphic structures (thick epidermis, hypodermis, and cuticle), a stomatal band, a developed vascular bundle, and a marginal resin duct. The xeromorphic structures become more pronounced with increasing altitude. The phytochemical and histochemical results demonstrate that the content of the main chemical compounds (phenols and terpenoids) basically increases at a higher elevation. Histochemical analysis localizes the phenols in epidermal cells, sponge tissue, endothelial layer cells, and stomatal bands, and the terpenoids in palisade tissue, sponge tissue, and the edge of the resin duct. This work reveals the relation between anatomy and chemistry in J. rigida needles, contributes to the quality control of its ethno-medicine, and provides the evidence to develop the commercial cultivation.

The importance of phenolic compounds for responding to various environmental conditions has been widely emphasized. However, the role of interactions between polyphenols and ecological factors, especially C, N, and P stoichiometry was little studied. Here, 15 sites across five provinces of Pinus bungeana in temperate regions of China were studied. The results showed that the higher values of total phenolic contents (TPC) of leaf and litter were distributed among the north distribution area of P. bungeana, lower values were in the south, whereas soil TPC were contrary to leaf and litter TPC. The stepwise regression, path analysis and decision index of path analysis for leaf TPC and ecological factors showed that altitude had the most direct impact on leaf TPC. Moreover, the principal determinants of leaf, litter and soil TPC were soil C/P ratios, longitude, and soil N/P ratios, respectively. In addition, the leaf, litter and soil TPC of P. bungeana were limited by soil C/N ratios, mean annual temperature, and soil P, respectively. Overall, our study provided evidence that ecological factors affected strongly the leaf, litter and soil TPC of P. bungeana.

Using Hg

ANXA1 and EphA2 play a crucial role in cancer. Here, we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination degradation in nasopharyngeal carcinoma (NPC), leading to the enhanced NPC growth and metastasis in vitro and in vivo . In human NPC, patients with the high expression of both ANXA1 and EphA2 proteins have poorer disease-free survival and overall survival relative to patients with the high expression of one protein alone. Furthermore, based on the N-terminal amino acid 20-30 region of ANXA1 responsible for binding EphA2, we develop an ANXA1-derived peptide, named as A1 (20-30), that cuts its connection with EphA2, successfully downregulates EphA2 and suppresses NPC oncogenicity in vitro and in vivo. These findings reveal that ANXA1, via binding and stabilizing EphA2, drives NPC growth and metastasis, and present a strategy for targeting EphA2 degradation and treating NPC with a peptide.

Abnormal level of alkaline phosphatase (ALP) activity has been linked to many diseases in human. The development of fluorescent molecular probes that can report the expression and activity of ALP in various biological systems will be extremely valuable. However, the in vivo monitoring for ALP in living cells and more complex biological systems remains a great challenge. The excited-state intramolecular proton transfer (ESIPT) probe with proportional fluorescence has low background noise, while the aggregation induced emission (AIE) probe has the advantages of signal amplification and good light stability. Herein, an “AIE + ESIPT” fluorescent probe 2-(benzo[d]thiazol-2-yl)-4-(1,4,5-triphenyl-1H-imidazole-2-yl)phenyl dihydrogen phosphate (THP) was constructed for the highly selective and sensitive detection of ALP. By introducing a phosphate ester at the hydroxyl position of the solid fluorophore 2-(benzo[d]thiazol-2-yl)-4-(1,4,5-triphenyl-1H-imidazole-2-yl)phenol, ESIPT was hindered and the probe present a faint blue fluorescence in DMSO solution. While ALP was introduced, causing the phosphate in THP hydrolyzed, and the ESIPT process was restored to yield a yellow fluorescence at 550 nm, thereby achieving proportionality detection. THP exhibited high selectivity and sensitively to ALP with low limit of detection (1.21228 U/L), and the reaction completed within 20 min. In addition, with its outstanding advantages of low biological toxicity and enzyme conversion characteristics, THP has been successfully applied to ALP imaging in living cells (Hela cells, A549 cells and Hek293 cells), and can provide in situ information on the reaction site. Therefore, THP has the potential for detecting ALP activity in biomedical application.

Acute pancreatitis is characterized by zymogen preactivation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions which contribute to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-arginine. CaMKII phosphorylation due to cytosolic calcium overload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanied by impaired autophagy correlated positively with intra-acinar cell digestive aymogen activation stimulated by cerulein or L-arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca2+ overload alleviation. We provide a promising therapy for acute pancreatitis through targeting both impaired autophagy and increased cytosolic calcium.

The radioresistance is the key factor to hamper curative effect and survival of nasopharyngeal carcinoma (NPC) patients. Nature triptolide (TPL) has been found to circumvent drug-resistant effect of cancer, but its effect on NPC radioresistance has been rarely studied. In the present study, the 10 Gy-resistant CNE2 subclones (CNE2-SR) were used as a NPC radioresistant model. The IC50 of TPL in CNE2 and CNE2-SR cells was measured by MTT assay, cell cycle was analyzed by flow cytometry, and protein expression was examined by western blot. Our data showed that TPL treatment decreased the percentage of viable cells, and IC50 value in CNE2 and CNE2-SR cells was 23.6 ± 1.41 nmol/L and 31.2 ± 1.16 nmol/L, respectively. Six Gy was a moderate dosage of X-ray for CNE2, and 25 nM TPL was close to IC50 value of CNE2 and CNE2-SR. Six Gy X-ray and/or 25 nM TPL significantly inhibited tumor growth in nude mice. Furthermore, 6 Gy X-ray and/or 25 nM TPL significantly inhibited cell growth and induced cell apoptosis and M/G2 phase arrest in CNE2 and CNE2-SR cells. Moreover, TPL treatment significantly inhibited the expression of GRP78 protein in CNE2 and CNE2-SR cells. These results suggest that TPL may serve as a potential radiosensitizer agent for NPC treatment.

Changes in white shrimp (Litopenaeus vannamei) protein during thermal denaturation were studied using Raman spectroscopy and isotopic H/D exchange. Denaturation of shrimp protein began after heating for 10 min at 50°C. A decrease in the percentage of α-helices accompanied by an increase in the percentage of β-sheets occurred while the total percentage of disordered structures increased. With extension of the exchange time, the relative intensity of the O-D bond increased, accompanied by a higher relative O-D bond intensity for heated shrimp, compared with unheated shrimp. H/D exchange revealed a higher rate of deuteration kinetics in heated shrimp than for unheated shrimp, especially during the first 2 h, consistent with water loss from denatured white shrimp protein. Physical property changes in muscle tissue can be caused by changes in hydrogen bonding and hydrophobicity during thermal processes.

Biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play pivotal roles in numerous physiological events, however, due to the similar structures and reactivities, differentiation of these biothiols remains a challenging task. Herein, we reported a maleimide-appended fluorescent probe ABTT-MA capable of specific sensing of Cys over other structure-alike biothiols with an ultralow detection limit (9.4 nM). Via a series of investigations into the mechanism, the high selectivity toward Cys is ascribed to a Michael addition/S,N-intramolecular rearrangement cascade reaction, in which the involvement of the mercapto and the adjacent amino groups is necessary to proceed the sensing process. Given this presupposition, Cys could be kinetically discriminated from Hcy and GSH. Upon the addition of Cys, a strong fluorescence appeared and the intensity at 503 nm was correlated with Cys concentration linearly over a wide range (0–10 μM). Thanks to the aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) activity, the selective detection of Cys was realized not only in aqueous media but in the paper-based point-of-care test (POCT). Significantly, the practicability of ABTT-MA in exogenous and endogenous Cys imaging in living cells was elucidated as well.

Podophyllotoxin (PPT) exhibits the various bioactive activities in the traditional treatment of many diseases. As the important ethnomedicine resources of China, PPT produced by Juniperus rigida could become a promising alternative sources of Podophyllum hexandrum, which is endangered by overcollection. However, it is unclear whether the genetic diversity of J. rigida is associated with its PPT contents for the different regions. To search the characteristic of J. rigida with high PPT contents and genetic diversities, the superior genotypes of J. rigida were researched by combing PPT profiles with SRAP molecular markers. The results showed that the higher contents of PPT of J. rigida were found in YJ (Shaanxi, 189.18 mg/g) and XDC (Hebei, 184.81 mg/g) and the lower in JHX (Jilin, 71.90 mg/g), CBS (Jilin, 94.92 mg/g) and LYM (Liaoning, 71.11 mg/g). The higher genetic diversity was found in two varieties of J. rigida (i.e., CBS (Jilin) and LYM (Liaoning)). To explore the relationship between the PPT profiles and genetic diversity, J. rigida from ten regions were divided into the same two groups distinguished by PPT contents and SRAP molecular marker, which were PPT contents in the Loess Plateau of China higher than that in the northeast of China. Specially, the contents of PPT exhibited an extremely significant positive correlation with geographic distance/genetic distance. These findings would not only provide a scientific basis for the selecting powerful source of high PPT genotypes of J. rigida in breeding research, but also made J. rigida a promising alternative source of PPT for the pharmaceutical industry.

Despite being highly emissive in solution, aggregation of 4-(4,5-bis(4-methoxyphenyl)-1H- imidazole-2-yl) benzaldehyde (BMI) molecules typically results in the quenching of fluorescence. To overcome the shortcomings of aggregation-caused quenching (ACQ), the substituent of imidazole in the nitrogen atom of the BMI have been found as a conformation function group (CFG) to turn the aggregation-induced emission (AIE) effect. The introduction of CFG not only causes the restriction of intramolecular rotations (RIR) effect, but also attenuates the coplanarity of the molecule. As a result, the BMI with ACQ effect is transformed into BMIs with AIE effect. As the steric hindrance of the CFG increases, the AIE characteristic of the derivative also becomes apparent. With the assistance of the thioacetal unit, BMIBD can act as an outstanding probe for the detection of Hg2+ with high sensitivity and selectivity. A series of characterizations were implemented to prove the unique response mechanism of BMIBD toward mercury ions, including optical behavior investigation, mass analysis and 1H NMR studies. Further, the detection limit is low up to 36 nM. Taking advantages of excellent optical properties of this AIE probe BMIBD, point-of-care testing (POCT) for Hg2+ detection was further investigated. Meanwhile, BMIBD presented the desirable analytical property for the real water samples. Additionally, cellular imaging experiment revealed that the probe has an excellent biocompatibility that could be applied for tracking Hg2+ in living cells.

The two hemispherical photographs (THP) method was used to calculate gap area. The areas of nine forest gaps were measured. Meanwhile, non-gap areas were selected as control groups with areas of 225 m2. Plots with areas of 25 m2 in five different directions within gap and non-gap areas were conducted for collecting leaf samples. To determine the effect of gap size on leaf traits the selected traits were leaf area (LA), leaf dry mass (LDM), specific leaf area (SLA), Chlorophyll a (Chl a), chlorophyll b (Chl b), total chlorophyll (TChl), and carotenoid (CAR). Leaves were collected from the regeneration layer (&lt, 2 cm DBH, height 2&ndash, 5 m) to measure the leaf traits in winter and summer seasons. Results confirmed significant positive correlations between LA and LDM in the small, medium, large gap sizes, and non-gap areas (r2 = 0.913, 0.827, 0.897, and 0.939, p &lt, 0.01, respectively). On the contrary, relationships between LDM and SLA in the small, medium, large gap sizes, and non-gap areas have significant negative correlations (r2 = &minus, 0.269, &minus, 0.259, &minus, 0.417, and &minus, 0.505, p &lt, 0.05, respectively). The effect of gap size on the average Chl a, Chl b, TChl, and CAR varies by the season. During the summer season, the highest chlorophyll contents were recorded in the small gap size and the lowest in the non-gap area, while during the winter season, the highest values of these chlorophyll contents appeared in the medium gap size. Moreover, the directions within the gap in the medium gap size of the summer season had an effect on the Chl a and TChl.

CD147 contributes to increased aerobic glycolysis through which it promotes tumor growth. Accumulating evidence suggests that CD147 exerts a variety of functions in thyroid cancer (TC) progression but the molecular mechanisms and therapeutic value of CD147 remain unclear.CD147 levels in TC tissues were analyzed to assess its relationship with prognosis and disease progression. A microRNA (miRNA) microarray and bioinformatics approach were used to identify microRNA regulators of CD147 through measurement of the expression and functions of these miRNAs in TC tissues and cell lines. Precursor miRNA-transfected cells were used to assess regulation of CD147 by miRNA. The effect of miRNA on TC cells via inhibition of glycolysis through CD147 targeting was also evaluated.We found that miR-125a-5p regulates CD147 and is negatively correlated with its expression and function. Moreover, CD147 knockdown or increased miR-125a-5p expression significantly reduced the viability, migration, and invasion of TC cells. Our mechanistic studies demonstrate that, through directly repressing the expression of the CD147 protein, miR-125a-5p suppresses aerobic glycolysis and lactate production and subsequently reduces TC cell viability, migration, and invasion, thereby exerting tumor suppressor functions.The novel connection identified between miR-125a-5p and CD147 suggests a new diagnostic and prognostic role for miR-125a-5p and that CD147 inhibition may be a candidate therapeutic target in the therapy of for TC.

Previous studies have shown that dysregulation of microRNA-150 (miR-150) is associated with aberrant proliferation of human non-small cell lung cancer (NSCLC) cells. However, whether miR-150 has a critical role in NSCLC cell metastasis is unknown. Here, we reveal that the critical pro-metastatic role of miR-150 in the regulation of epithelial-mesenchymal-transition (EMT) through down-regulation of FOXO4 in NSCLC. In vitro, miR-150 targets 3′UTR region of FOXO4 mRNA, thereby negatively regulating its expression. Clinically, the expression of miR-150 was frequently up-regulated in metastatic NSCLC cell lines and clinical specimens. Contrarily, FOXO4 was frequently down-regulated in NSCLC cell lines and clinical specimens. Functional studies show that ectopic expression of miR-150 enhanced tumor cell metastasis in vitro and in a mouse xenograft model, and triggered EMT-like changes in NSCLC cells (including E-cadherin repression, N-cadherin and Vimentin induction, and mesenchymal morphology). Correspondingly, FOXO4 knockdown exhibited pro-metastatic and molecular effects resembling the effect of miR-150 over-expression. Moreover, NF-κB/snail/YY1/RKIP circuitry regulated by FOXO4 were likely involved in miR-150-induced EMT event. Simultaneous knockdown of miR-150 and FOXO4 abolished the phenotypic and molecular effects caused by individual knockdown of miR-150. Therefore, our study provides previously unidentified pro-metastatic roles and mechanisms of miR-150 in NSCLC.

Spautin-1 Ameliorates Acute Pancreatitis via inhibiting impaired Autophagy and Alleviating Calcium Overload