Rational design of a near-infrared dual-emission fluorescent probe for ratiometric imaging of glutathione in cells.

Sensors for which the output signal is an intensity change for a single-emission peak are easily disturbed by many factors, such as the stability of the instrument, intensity of the excitation light, and biological background. However, for ratiometric fluorescence sensors, the output signal is a change in the intensity ratio of two or more emission peaks. The fluorescence intensity of these emission peaks is similarly affected by external factors; thus, these sensors have the ability to self-correct, which can greatly improve the accuracy and reliability of the detection results. To accurately image glutathione (GSH) in cells, gold nanoclusters (AuNCs) with intrinsic double emission at wavelengths of 606 nm and 794 nm were synthesized from chloroauric acid. With the emission peak at 606 nm as the recognition signal and the emission peak at 794 nm as the reference signal, a near-infrared dual-emission ratio fluorescence sensing platform was constructed to accurately detect changes in the GSH concentration in cells. In vitro and in vivo analyses showed that the ratiometric fluorescent probe specifically detects GSH and enables ultrasensitive imaging, providing a new platform for the accurate detection of active small molecules.

Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe.

Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.

mRNA-activated DNAzyme nanoprobe for tumor cell precise imaging and gene therapy.

A novel Au-nucleic acid nanoprobe, catalyzed by mRNA, has been developed for live cell imaging and precise treatment of tumor cells. This nanoprobe exhibits the remarkable ability to differentiate between tumor cells and normal cells through live cell mRNA imaging, while selectively inducing apoptosis in tumor cells.

CenhANCER: a comprehensive cancer enhancer database for primary tissues and cell lines.

Enhancers, which are key tumorigenic factors with wide applications for subtyping, diagnosis and treatment of cancer, are attracting increasing attention in the cancer research. However, systematic analysis of cancer enhancers poses a challenge due to the lack of integrative data resources, especially those from tumor primary tissues. To provide a comprehensive enhancer profile across cancer types, we developed a cancer enhancer database CenhANCER by curating public resources including all the public H3K27ac ChIP-Seq data from 805 primary tissue samples and 671 cell line samples across 41 cancer types. In total, 57 029 408 typical enhancers, 978 411 super-enhancers and 226 726 enriched transcription factors were identified. We annotated the super-enhancers with chromatin accessibility regions, cancer expression quantitative trait loci (eQTLs), genotype-tissue expression eQTLs and genome-wide association study risk single nucleotide polymorphisms (SNPs) for further functional analysis. The identified enhancers were highly consistent with accessible chromatin regions in the corresponding cancer types, and all the 10 super-enhancer regions identified from one colorectal cancer study were recapitulated in our CenhANCER, both of which testified the high quality of our data. CenhANCER with high-quality cancer enhancer candidates and transcription factors that are potential therapeutic targets across multiple cancer types provides a credible resource for single cancer analysis and for comparative studies of various cancer types. Database URL http://cenhancer.chenzxlab.cn/.

A Novel Fluorescent Aptamer Sensor with DNAzyme Signal Amplification for the Detection of CEA in Blood.

Carcinoembryonic antigen (CEA) is a tumor-specific biomarker; however, its low levels in the early stages of cancer make it difficult to detect. To address the need for analysis of ultra-low-level substances, we designed and synthesized a fluorescent aptamer sensor with DNAzyme signal amplification and used it for the detection of CEA in blood. In the presence of the target protein, the aptamer sequence in the recognition probe binds to the target protein and opens the hairpin structure, hybridizes with the primer and triggers a polymerization reaction in the presence of polymerase to generate double-stranded DNA with two restriction endonuclease Nb.BbvCl cleavage sites. At the same time, the target protein is displaced and continues to bind to another recognition probe, triggering a new round of polymerization reaction, forming a cyclic signal amplification triggered by the target. The experimental results show that the blood detection with CEA has a high sensitivity and a wide detection range. The detection range: 10 fg/mL~10 ng/mL, with a detection limit of 5.2 fg/mL. In addition, the sensor can be used for the analysis of complex biological samples such as blood.

Circ_0001777 Affects Triple-negative Breast Cancer Progression Through the miR-95-3p/AKAP12 Axis.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is 1 of the most serious cancer. Circular RNA_0001777 (circ_0001777) expression was decreased in TNBC tissues. However, the molecular mechanism of circ_0001777 remains unknown. METHODS: The expression of circ_0001777, microRNA-95-3p (miR-95-3p) and A-kinase anchor protein 12 (AKAP12) were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). A series of in vitro experiments were designed to explore the function of circ_0001777 in TNBC cells and the regulatory mechanism between circ_0001777 and miR-95-3p and AKAP12 in TNBC cells. Western blot examined the relative protein levels in TNBC cells. Bioinformatics prediction site predicted the relationship between miR-95-3p and circ_0001777 or AKAP12 and was verified by Dual-luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0001777 in vivo. RESULTS: The expression of circ_0001777 and AKAP12 was decreased in TNBC tissues, while the expression of miR-95-3p was increased. Circ_0001777 can sponge miR-95-3p, and AKAP12 is the target of miR-95-3p. In vitro complement experiments, overexpression of circ_0001777 significantly decreased the malignant behavior of TNBC, while co-transfection of miR-95-3p partially up-regulated this change. In addition, AKAP12 knockdown increased the proliferation, migration, and invasion of TNBC cells inhibited by overexpression of circ_0001777. Mechanically, circ_0001777 regulates AKAP12 expression in TNBC cells by sponge miR-95-3p. In addition, in vivo studies have shown that overexpression of circ_0001777 inhibits tumor growth. CONCLUSION: Overexpression of circ_0001777 decreased proliferation, migration, and invasion of TNBC cells by regulating the miR-95-3p/AKAP12 axis, suggesting that circ_0001777/miR-95-3p/AKAP12 axis may be a potential regulatory mechanism for the treatment of TNBC.

[Protective effect and mechanism of electroacupuncture of "Biao-Ben" acupoints combination for mitochondrial dysfunction in diabetic nephropathy rats].

OBJECTIVE: To study the protective effect of electroacupuncture (EA) at "Biao"-acupoints, "Fenglong"(ST40) and "Zhongwan"(CV12), used for treating symptoms of the disease, and "Ben"-acupoints, "Zusanli"(ST36) and "Guanyuan"(CV4), for treating the root cause of the disease on oxidative stress injury of renal mitochondria through SIRT1/PGC-1α signal pathway in rats with diabetic nephropathy (DN). METHODS: A total of 33 male Wistar rats were randomized into normal (n=10), model (n=12) and EA (n=11) groups.The DN model was established by feeding the rats with high-sugar and high-fat diet for 6 weeks combined with streptozotocin (STZ, 35 mg/kg, i.p.). EA (4 Hz/60 Hz, 1 mA)was applied to ST36-ST40 and CV4-CV12 for 15 min, once every other day for 8 weeks. The rats' body weight was recorded, urine in 24 hours (24-h UP) was collected to measure the urine protein level, and the fasting blood glucose (FBG) level detected by using a glucometer. The levels of serum glycosylated hemoglobin (HbA1c), creatinine (Scr) and urea nitrogen (BUN) were assayed using immunoturbidi-metry, picric acid method and urease method, respectively, and those of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) detected using an automatic biochemical analyzer. The kidney tissue was collected for assaying the activity of superoxide dismutase (SOD) with xanthine oxidase method, glutathione (GSH) activity with dithio-dinitrobenzoic acid method, catalase （CAT） activity with ammonium molybdate spectrometric method, and malondialdehyde (MDA) content with thiobarbituric acid method. Histopathological changes of the kidney tissue were observed by microscope after hematoxylin-eosin staining (HE), periodate Schiff staining (PAS) and Masson staining, separately, and its subcellular structure was observed under transmission electron microscopy. The expression levels of renal SIRT1 and PGC-1α mRNAs and proteins were detected by quantitative real-time PCR and Western blot, and the immunoactivity of renal α-smooth muscle actin (α-SMA), and immunofluorescence density of renal collagen Ⅰ (Col Ⅰ), collagen Ⅳ(Col Ⅳ) and fibronec-tin (FN) detected by immunohistochemistry and immunofluorescence assay, respectively. RESULTS: Compared with the normal group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C, MDA, α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were significantly increased (P<0.01), and the levels of body weight, HDL-C, SOD, GSH, CAT, SIRT1 and PGC-1α mRNAs and proteins were decreased in the model group (P<0.01, P<0.05). In comparison with the model group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C and MDA, and the expressions of α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were markedly down-regulated (P<0.05, P<0.01), and those of body weight, HDL-C, SOD, GSH, CAT, and the expressions of SIRT1 and PGC-1α mRNAs and proteins significantly up-regulated (P<0.01, P<0.05) in the EA group. HE staining showed mesangial dilatation, glomerular hypertrophy and mesangial matrix accumulation; PAS staining showed an increase of the glomerular extracellular matrix deposition; and Masson staining displayed an enhancement of glomerular fibrosis and interstitial space expansion; and electron microscope revealed foot process fusion, basement membrane thickening and organelle injury in the rat's kidney of the model group, which were relatively milder in the EA group. CONCLUSION: EA of ST36-ST40 and CV4-CV12, "Biao-Ben" acupoints combination, can alleviate oxidative stress and mitochondrial dysfunction in DN rats, which may be associated with its functions in up-regulating SIRT1/PGC-1α signaling, and decreasing renal fibrosis.

[Electroacupuncture preconditioning alleviates renal injury and oxidative stress through Sirt3/MnSOD pathway in type 2 diabetic rats].

OBJECTIVE: To explore the protective effect and molecular mechanism of electroacupuncture (EA) preconditioning on renal injury in type 2 diabetic rats. METHODS: Fifty male Wistar rats were randomly divided into control, model, EA, EA+inhibitor, and inhibitor groups, with 10 rats in each group. Diabetes model was established by high fat and high glucose diet and intraperitoneal injection of streptozotocin (40 mg/kg). EA (2 Hz, 1 mA) preconditioning was applied to "Guanyuan" (CV4), "Zhongwan" (CV12), bilateral "Zusanli" (ST36) and "Fenglong" (ST40) for 15 min, once every other day for 8 weeks. Rats of the inhibitor and EA+inhibitor groups were given intraperitoneal injection of 3-TYP (50 mg/kg) once every other day for a total of 3 times. The body weight, kidney mass, and renal index were recorded. The contents of urine microalbumin (ALB), 24 h urine 8-hydroxydeoxyguanosine (8-OHdG) and activities of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione glycine peroxidase (GSH-Px) in kidney were detected by ELISA. The activities of mitochondrial respiratory chain enzyme complex (RCCⅠ-RCCⅣ) in kidney were detected using spectrophotometric method. HE staining, Masson staining and transmission electron microscopy were used to observe the changes of renal structure. The protein and mRNA expressions of silent information regulator 3 (Sirt3), manganese superoxide dismutase (MnSOD) in kidney were detected by Western blot and quantitative real-time PCR, respectively. RESULTS: After modeling and compared with the control group, the contents of ALB, the renal index, activity of ROS and content of 8-OHdG, and the renal collagen volume fraction (CVF) were increased (P<0.01), while the activities of SOD, CAT and GSH-Px, RCCⅠ-RCCⅣ, and the mRNA and protein expressions of Sirt3 and MnSOD were decreased (P<0.01). After the treatment and compared with the model group, the contents of ALB, the renal index, ROS, 8-OHdG, and the CVF were decreased in the EA group(P<0.01, P<0.05), while the activities of SOD, CAT, GSH-Px, RCCⅠ-RCCⅣ, and Sirt3 and MnSOD expression levels were increased (P<0.01, P<0.05)；the RCCⅡ activity and the expression level of MnSOD mRNA were increased (P<0.05) in the EA+inhibitor group; the ALB and 8-OHdG contents and the CVF in the inhibitor group were increased (P<0.05), while the activity of SOD, and Sirt3 and MnSOD expression levels were decreased (P<0.05). In comparison with the EA group, the contents of ALB, the renal index, activities of ROS and 8-OHdG contents, and the CVF were increased (P<0.05, P<0.01), activities of SOD, CAT and GSH-Px and RCCⅠ and RCCⅡ, and the mRNA and protein expressions of Sirt3 and MnSOD were decreased (P<0.05, P<0.01) in both EA+inhibitor group and inhibitor group, whereas the activities of RCCⅢ and RCCⅣ were decreased in the inhibitor group (P<0.05). The therapeutic effect of inhibitor was notably inferior to that of EA+inhibitor in decreasing ALB and 8-OHdG contents, and CVF (P<0.01), and in up-regulating SOD and RCCⅡ activities, Sirt3 and MnSOD expression levels (P<0.01, P<0.05). CONCLUSION: EA preconditioning can increase the expressions of renal Sirt3 and MnSOD in type 2 diabetic rats, thereby reducing the oxidative stress response and protecting the kidneys.

Astramalabaricosides A-T, Highly Oxygenated Malabaricane Triterpenoids with Migratory Inhibitory Activity from Astragalus membranaceus var. mongholicus.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

[Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period].

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION: The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.

DSEATM: drug set enrichment analysis uncovering disease mechanisms by biomedical text mining.

Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.

Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.

Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, the mechanisms for transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory factors for colitis-associated cancer. Here, a systematic epigenomic study of histone modifications is performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM-DSS-induced CRC mouse model. In combination with transcriptomic data, the authors generate a dataset of 105 deep sequencing files and illustrate the dynamic landscape of chromatin states at five time points during inflammation-cancer transition. Functional gene clusters are identified based on dynamic transcriptomic and epigenomic information, and key signaling pathways in the process are illustrated. This study's results reveal that enhancer state regions play important roles during inflammation-cancer transition. It predicts novel transcription factors based on enhancer information, and experimentally proves OTX2 as a critical tumor suppressive transcription factor. Taken together, this study provides comprehensive epigenomic data and reveals novel molecular mechanisms for colitis-associated cancer.

[Effect of electroacupuncture of "Biao-Ben" acupoints on renal function and hemorheology and eNOS level in patients with early diabetic nephropathy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Biao-Ben acupoints" (Biao indicates pathogenic factors of disease; Ben refers to body constitution) on renal function, hemorheology and endothelial nitric oxide synthase (eNOS) level in patients with early diabetic kidney disease (DKD), so as to explore its mechanism underlying relieving early DKD. METHODS: A total of 120 patients with early DKD were selected and randomized into 3 groups: medication, conventional acupoints, and "Biao-Ben"acupoints groups by stratified randomization method, with 40 cases in each group. Patients of the me-dication group were treated by routine symptomatic supportive treatment (gleziquantel tablets or subcutaneous injection of insulin \[for hyperglycemia\], candesartan tablet \[hypertension\], simvastatin tablets \[hyperlipidemia\], etc.).Based on the medication group, patients of the conventional acupoint group were treated by EA of bilateral Feishu (BL13), Weiwanxiashu (EX-B3), Weishu (BL21), Shenshu (BL23), Sanyinjiao (SP6), Taixi (KI3) (main acupoints), etc., and those of the Biao-Ben acupoint group treated by EA of main acupoints Zhongwan (CV12), Fenglong (ST40), Xuehai (SP10) and Taichong (LR3) (Biao acupoints), and Guanyuan (CV4) and Zusanli (ST36) (Ben acupoints). The EA treatment was conducted one daily, 5 days a week for 8 weeks. The urine microprotein level in 24 h was detected using an automatic specific protein analyzer, followed by calcula-ting the urine albumin excretion rate (UAER). The serum creatinine (Scr), urea nitrogen (BUN) and cystatin (CysC) contents were detected by using an automatic biochemical analyzer, and the whole blood low-cut viscosity (ηbL), whole blood mid-cut viscosity (ηbM), whole blood high-cut viscosity (ηbH), plasma viscosity (ηp) and fibrinogen (FIB) levels were detected using an automatic hemorheology tester, and the serum eNOS and nitric oxide (NO) levels assayed using enzyme linked immunosorbent assay. The total clinical effective rates were compared and the adverse reactions of the treatment were recorded. RESULTS: Compared with the values before the treatment in each group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were all significantly decreased (P<0.01), while serum eNOS and NO levels significantly increased in the three groups after the treatment (P<0.01). Compared with the medication group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were notably lower (P<0.01, P<0.05), and serum eNOS and NO contents obviously higher in both the conventional acupoint and "Biao-Ben" acupoint groups (P<0.01). Comparison between the two EA groups showed that the levels of UAER, BUN, ηbL, ηbM, ηbH and ηp were lower (P<0.05), whereas the serum eNOS and NO contents were considerably higher (P<0.05) in the "Biao-Ben" acupoint group than in the conventional acupoint group. After the treatment, the total clinical effective rate of the "Biao-Ben" acupoint group was 89.74%(35/39), being significantly higher than those of both the conventional acupoint group (71.05%, 27/38,P<0.05) and medication group (64.10%, 25/39, P<0.05). CONCLUSION: EA of "Biao-Ben" acupoints can improve renal function and reduce microcirculation disorders in patients with early DKD, which may be related to its function in up-regulating the levels of serum eNOS and NO.

Fortification of set yogurt with passion fruit juice: Effects on fermentation kinetics, physicochemical properties, and functionality.

With the purpose of developing an alternative set yogurt with high consumer acceptability, passion fruit juice, at levels that varied from 0 to 10%, was incorporated into set yogurt, and the effects on the fermentation kinetics, physicochemical properties, and functionality of set yogurt were evaluated. The results showed that the addition of passion fruit juice was simultaneously propitious for milk acidification in earlier fermentation stages and reduced the fermentation rate at later stages of fermentation. The phenolic compounds and pectin in passion fruit juice interacted with caseins to form soluble complexes, enhancing the gel strength of set yogurts by 7.5%. The aroma and flavor of the set yogurt was improved as well. However, with the addition of 10% passion fruit juice, the gel structure was destroyed, and the quality of the set yogurt was very degraded. More importantly, the addition of passion fruit juice increased the polyphenol content and significantly enhanced the antioxidant activity of the set yogurt. This investigation demonstrated the feasibility of fabricating passion fruit juice-enriched set yogurt and its superior quality compared with the corresponding normal product.

Revealing the Charge Storage Mechanism of Nickel Oxide Electrochromic Supercapacitors.

Nickel oxide (NiO) is considered one of the most promising positive anode materials for electrochromic supercapacitors. Nevertheless, a detailed mechanism of the electrochromic and energy storage process has yet to be unraveled. In this research, the charge storage mechanism of a NiO electrochromic electrode was investigated by combining the in-depth experimental and theoretical analyses. Experimentally, a kinetic analysis of the Li-ion behavior based on the cyclic voltammetry curves reveals the major contribution of surface capacitance versus total capacity, providing fast reaction kinetics and a highly reversible electrochromic performance. Theoretically, our model uncovers that Li ions prefer to adsorb at fcc sites on the NiO(1 1 1) surface, then diffuse horizontally over the plane, and finally migrate in the bulk. More significantly, the calculated theoretical surface capacity (106 mA h g-1) accounts for about 77.4% of the total experimental capacity (137 mA h g-1), indicating that the surface storage process dominates the whole charge storage, which is in accordance with the experimental results. This work provides a fundamental understanding of transition-metal oxides for application in electrochromic supercapacitors and can also promote the exploration of novel electrode materials for high-performance electrochromic supercapacitors.

Preparation of "Ion-Imprinting" Difunctional Magnetic Fluorescent Nanohybrid and Its Application to Detect Cadmium Ions.

In this work, we have fabricated a novel difunctional magnetic fluorescent nanohybrid (DMFN) for the determination of cadmium ions (Cd2+) in water samples, where the "off-on" model and "ion-imprinting" technique were incorporated simultaneously. The DMFN were composed of CdTe/CdS core-shell quantum dots (QD) covalently linked onto the surface of polystyrene magnetic microspheres (PMM) and characterized using ultraviolet-visible spectroscopy (UV-Vis), fluorescence spectroscopy, and transmission electron microscopy (TEM). Based on the favorable magnetic and fluorescent properties of the DMFN, the chemical etching of ethylene diamine tetraacetic acid (EDTA) at the surface produced specific Cd2+ recognition sites and quenched the red fluorescence of outer CdTe/CdS QD. Under optimal determination conditions, such as EDTA concentration, pH, and interfering ions, the working curve of determining Cd2+ was obtained; the equation was obtained Y = 34,759X + 254,894 (R = 0.9863) with a line range 0.05-8 µM, and the detection limit was 0.01 µM. Results showed that synthesized magnetic fluorescent microspheres had high sensitivity, selectivity, and reusability in detection. Moreover, they have significant potential value in fields such as biomedicine, analytical chemistry, ion detection, and fluorescence labeling.

Anti-masculinization induced by aromatase inhibitors in adult female zebrafish.

BACKGROUND: Early sex differentiation genes of zebrafish remain an unsolved mystery due to the difficulty to distinguish the sex of juvenile zebrafish. However, aromatase inhibitors (AIs) could direct juvenile zebrafish sex differentiation to male and even induce ovary-to-testis reversal in adult zebrafish. RESULTS: In order to determine the transcriptomic changes of sex differentiation in juvenile zebrafish and early sex-reversal in adult zebrafish, we sequenced the transcriptomes of juvenile and adult zebrafish treated with AI exemestane (EM) for 32 days, when juvenile zebrafish sex differentiation finished. EM treatment in females up-regulated the expression of genes involved in estrogen metabolic process, female gamete generation and oogenesis, including gsdf, macf1a and paqr5a, while down-regulated the expression of vitellogenin (vtg) genes, including vtg6, vtg2, vtg4, and vtg7 due to the lower level of Estradiol (E2). Furthermore, EM-juveniles showed up-regulation in genes related to cell death and apoptosis, such as bcl2l16 and anax1c, while the control-juveniles exhibited up-regulation of genes involved in positive regulation of reproductive process and oocyte differentiation such as zar1 and zpcx. Moreover, EM-females showed higher enrichment than control females in genes involved in VEGF signaling pathway, glycosaminoglycan degradation, hedgehog signaling pathway, GnRH signaling pathway and steroid hormone biosynthesis. CONCLUSIONS: Our study shows anti-masculinization in EM-treated adult females but not in EM-treated juveniles. This may be responsible for the lower sex plasticity in adults than juveniles.

Galvanic replacement mediated 3D porous PtCu nano-frames for enhanced ethylene glycol oxidation.

Three dimensional (3D) porous PtCu nano-frames with a unique hollow structure were obtained after a galvanic replacement reaction, exhibiting a high normalized mass activity of 23.1 A m-2 µg-1 towards ethylene glycol oxidation with excellent stability. The morphological evolution and catalytic mechanism were detailed.

Two telomerase-targeting Pt(ii) complexes of jatrorrhizine and berberine derivatives induce apoptosis in human bladder tumor cells.

Two novel Pt(ii) complexes, [Pt(B-TFA)Cl]Cl (Pt1) and [Pt(J-TFA)Cl]Cl (Pt2) with jatrorrhizine and berberine derivatives (B-TFA and J-TFA) were first prepared as desirable luminescent agents for cellular applications and potent telomerase inhibitors, which can induce bladder T-24 tumor cell apoptosis by targeting telomerase, together with induction of mitochondrial dysfunction, telomere DNA damage and cell-cycle arrest. Importantly, T-24 tumor inhibition rate (TIR) was 50.4% for Pt2, which was higher than that of Pt1 (26.4%) and cisplatin (37.1%). Taken together, all the results indicated that jatrorrhizine and berberine derivatives Pt1 and Pt2 show low toxicity and could be novel Pt-based anti-cancer drug candidates.

Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic Disease Genes.

Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most diseases are not caused by a single pathogenic factor, but by multiple disease genes, in particular, interacting disease genes. Thus, it is reasonable to consider that targeting epistatic disease genes may enhance the therapeutic effects of combinatorial drugs. In this study, synthetic lethality gene pairs of tumors, similar to epistatic disease genes, were first targeted by combinatorial drugs, resulting in the enrichment of the combinatorial drugs with cancer treatment, which verified our hypothesis. Then, conventional epistasis detection software was used to identify epistatic disease genes from the genome wide association studies (GWAS) dataset. Furthermore, combinatorial drugs were predicted by targeting these epistatic disease genes, and five combinations were proven to have synergistic anti-cancer effects on MCF-7 cells through cell cytotoxicity assay. Combined with the three-dimensional (3D) genome-based method, the epistatic disease genes were filtered and were more closely related to disease. By targeting the filtered gene pairs, the efficiency of combinatorial drug discovery has been further improved.