Enhancing Chymotrypsin Activity and Stability of Capillary Immobilized Enzyme Microreactors Using Zeolitic Imidazolate Frameworks as Encapsulation Materials.

Open-tubular immobilized enzyme microreactors (OT-IMERs) are some of the most widely used enzyme reaction devices due to the advantages of simple preparation and fast sample processing. However, the traditional approaches for OT-IMERs preparation had some defects such as limited enzyme loading amount, susceptibility to complex sample interference, and less stability. Here, we report a strategy for the preparation of highly active and stable OT-IMERs, in which the single-stranded DNA-enzyme composites were immobilized in capillaries and then encapsulated in situ in the capillaries via zeolitic imidazolate frameworks (ZIF-L). The phosphate groups of the DNA adjusted the surface potential of the enzyme to negative values, which could attract cations, such as Zn2+, to promote the formation of ZIF-L for enzyme encapsulation. Using chymotrypsin (ChT) as a model enzyme, the prepared ChT@ZIF-L-IMER has higher activity and better affinity than the free enzyme and ChT-IMER. Moreover, the thermal stability, pH stability, and organic solvent stability of ChT@ZIF-L-IMER were much higher than those of free enzyme and ChT-IMER. Furthermore, the activity of ChT@ZIF-L-IMER was much higher than that of ChT-IMER after ten consecutive reactions. To demonstrate the versatility of this preparation method, we replaced ChT with glucose oxidase (GOx). The stability of GOx@ZIF-L-IMER was also experimentally demonstrated to be superior to that of GOx and GOx-IMER. Finally, ChT@ZIF-L-IMER was used for proteolytic digestion analysis. The results showed that ChT@ZIF-L-IMER had a short digestion time and high digestive efficiency compared with the free enzyme. The present study broadened the synthesis method of OT-IMERs, effectively integrating the advantages of metal-organic frameworks and IMER, and the prepared OT-IMERs significantly improved enzyme stability. All of the results indicated that the IMER prepared by this method had a broad application prospect in capillary electrophoresis-based high-performance enzyme analysis.

Hollow Cu/CoS2 Nanozyme with Defect-Induced Enzymatic Catalytic Sites and Binding Pockets for Highly Sensitive Fluorescence Detection of Alkaline Phosphatase.

Along with an ever-deepening understanding of the catalytic principle of natural enzymes, the rational design of high-activity biomimetic nanozymes has become a hot topic in current research. Inspired by the active centers of natural enzymes consisting of catalytic sites and binding pockets, a Cu-doped CoS2 hollow nanocube (Cu/CoS2 HNCs) nanozyme integrating substitution defects and vacancies is developed through a defect engineering strategy. It is shown that the vacancies and substitution defects in the developed Cu/CoS2 HNC nanozymes serve as binding pockets and catalytic sites, respectively. The construction of this key active center and the accelerated electron transfer from the Co/Cu redox cycle significantly improve the substrate affinity and catalytic efficiency of the Cu/CoS2 HNCs nanozymes, which results in the excellent catalytic performance of the Cu/CoS2 HNC nanozymes. Using the superior enzymatic activity of Cu/CoS2 HNCs, a fluorescence detection platform for alkaline phosphatase (ALP) is established, which is a wider detection range and lower limit of detection (LOD) than previous work. This work broadens the family of nanozymes and provide a new idea for the development of novel nanozymes with high enzyme activity, as well as a guideline for the construction of highly sensitive fluorescent sensors.

Exploring charge generation and separation in tandem organic light-emitting diodes based on magneto-electroluminescence.

5,6,11,12-tetraphenylnaphthacene (rubrene) exhibits resonant energy properties (ES1,rub≈ 2ET1,rub), resulting in rubrene-based organic light-emitting diode (OLED) devices that undergo the singlet fission (STT) process at room temperature. This unique process gives rise to a distinct magneto-electroluminescence (MEL) profile, differing significantly from the typical intersystem crossing (ISC) process. Therefore, in this paper, we investigate charge generation and separation in the interconnector, and the mechanism of charge transport in tandem OLEDs at room temperature using MEL tools. We fabricate tandem OLEDs comprising green (Alq3) and yellow (Alq3:rubrene) electroluminescence (EL) units using different interconnectors. The results demonstrate that all devices exhibited significant rubrene emission. However, the MEL did not exhibit an STT process with an increasing magnetic field, but rather a triplet-triplet annihilation (TTA) process. This occurrence is attributed to direct carrier trapping within doped EL units, which hinders the transport of rubrene trapped charges, consequently prolonging the lifetime of triplet excitons (T1,rub). Thus, the increased T1,rubconcentration causes TTA to occur at room temperature, causing the rapid decrease of MEL in all devices under high magnetic fields. In devices where only the TTA process occurs, the TTA increases with the increasing current. Consequently, the high magnetic field of devices A-C is only related to TTA. Notably, there exists a high magnetic field TTA of device D in the Alq3/1,4,5,8,9,11-Hexaazatriphenylene-hexacarbonitrile interconnector regardless of the current. This occurs because both EL units in the device emit simultaneously, resulting in the triplet-charge annihilation process of Alq3in the high magnetic field of the MEL. Moreover, the rapid increase in MEL at low magnetic field across all devices is attributed to the ISC between Alq3polaron pairs. This entire process involves Förster and Dexter energy transfer. This article not only provides novel insights into charge generation and separation in the interconnector but also enhances our understanding of the microscopic mechanisms in tandem OLED devices.

Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

Realizing high efficiency and luminance in green, yellow and blue organic light emitting diode by deoxyribonucleic acid.

Although the effect of the electron blocking layer (EBL) material, deoxyribonucleic acid (DNA), on the electroluminescence (EL) performance of organic light-emitting diodes (OLEDs) has been studied, the process of DNA regulation of exciton recombination region within the device is still unclear. Herein, devices with and without EBL were fabricated using different DNA spin-coating speeds, and the photoelectric performance of device were measured. By using DNA compounded with cetyltrimethyl ammonium (CTMA) as the EBL and hole buffer layer, so-called BioLEDs. The DNA-based green Alq3BioLEDs achieve higher luminance (39 000 cd m-2) and higher current efficiency (8.4 cd A-1), which are increased by 49% and 54%, respectively, compared to the reference OLEDs without the addition of DNA. Similarly, the maximum luminance and efficiency of yellow Rubrene BioLEDs is increased by 64% (from 12 120 to 19 820 cd m-2) and 74% (from 1.36 to 2.36 cd A-1), the luminance and efficiency of blue TCTA BioLEDs is increased by 101% and 245%. Specifically, we found that as the thickness of DNA-CTMA increases, the exciton recombination region moves towards the interface between the emitting layer (EML) and the hole transport layer (HTL). By better confining excitons within the EML, the current efficiency of the BioLEDs is effectively improved. Accordingly, we provide a possible idea for achieve high performance DNA-based BioLEDs by adding DNA-CTMA EBL and hole buffer layers. Meanwhile, as the DNA thickness increases, the exciton recombination region moves towards the EML/HTL interface, thereby enhancing the efficiency of the DNA-based BioLEDs.

A potential primary method for peptide purity analysis by gas chromatography-isotope dilution infrared spectrometry.

Here we proposed a method for peptide purity analysis using gas chromatography-isotope dilution infrared spectroscopy. The principle and feasibility of the proposed measurement method were investigated. The derivatization, separation, and infrared detection conditions for amino acids were optimized, and the performance of the method was investigated. Then, the proposed method was used for assessment of [Glu1]-fibrinopeptide B purity, and the results were compared with those obtained by high performance liquid chromatography-isotope dilution mass spectrometry. The average purity of six sub-samples using the proposed method was (0.755 ± 0.017) g/g, which agreed well with that obtained by isotope dilution mass spectrometry (0.754 ± 0.012) g/g. The repeatability of the proposed method was 2.2%, which was similar to that of isotope dilution mass spectrometry (1.7%). The proposed method has a similar principle and had similar accuracy, precision, and linearity to isotope dilution mass spectrometry; however, the developed method had higher limit of detection (LOD) and limit of quantitation (LOQ) values because of the low sensitivity of infrared detection. The results were also Système International d'Unités (SI) traceable. The developed method has the advantage of lower cost compared with isotope dilution mass spectrometry because only one isotope-labeled atom in an analog is required, and several infrared spectra can be extracted, averaged, and used for an amino acid calculation during one run, potentially leading to higher accuracy. This method could be easily expanded to the accurate quantitation of other organic compounds, including proteins. It is expected that the proposed method will be widely used in chemical and biological measurements as a new primary method.

Investigations on exciton recombination and annihilation in TmPyPB-ETL OLEDs using magnetic field effects.

Although the effect of the electron transport layer (ETL) material TmPyPb on the electroluminescence performance of organic light-emitting diodes (OLEDs) has been extensively studied, the process of TmPyPb regulating exciton recombination and annihilation within the device is still unclear. Here, we fabricated devices of various TmPyPb thicknesses with and without ETL. Subsequently, we measured the magneto-electroluminescence (MEL) of these devices. Specifically, at the same luminance, the triplet-charge annihilation (TQA) process is more likely to occur as the thickness of TmPyPb increases, resulting in a decrease in the maximum luminance of devices. Due to electron leakage and exciton recombination region moving towards the cathode, leading to a decrease in luminance efficiency at first and then an enhancement with an increase in the thickness of TmPyPb. Furthermore, at room temperature, the application of a large bias voltage suppresses singlet fission (SF) processes by modulating the dissociation of singlet polaron pairs (PPS) and the concentration of triplet exciton (T1). This leads to the conversion of SF to the TQA process. At low temperatures, the bias voltage and temperature can regulate the concentration and lifetime of PPS and T1. Therefore, as the temperature decreases, the transition of SF → TQA → triplet-triplet annihilation (TTA) and TQA coexistence → TTA process occurs. Moreover, MEL responses of the TmPyPb-ETL device show a W-linear pattern owing to the combined effect of the hyperfine interaction (HFI) and Zeeman splitting at 145 K. Accordingly, we explored the electroluminescence (EL) performance of TmPyPB-ETL OLEDs and investigated the evolution of SF, TQA, and TTA processes using MEL. Our study revealed the effect of exciton recombination and annihilation in OLEDs with varying thicknesses of TmPyPb.

Exercise improves cognitive dysfunction and neuroinflammation in mice through Histone H3 lactylation in microglia.

BACKGROUND: Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory. RESULTS: Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype. CONCLUSION: The elevated lactate acted as an "accelerator" of the endogenous "lactate timer" in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.

Alfalfa MsATG13 Confers Cold Stress Tolerance to Plants by Promoting Autophagy.

Autophagy is a conserved cellular process that functions in the maintenance of physiological and metabolic balance. It has previously been demonstrated to improve plant tolerance to abiotic stress. Numerous autophagy-related genes (ATGs) that regulate abiotic stress have been identified, but there have been few functional studies showing how ATGs confer cold stress tolerance. The cold transcriptome data of the crown buds that experienced overwintering of the alfalfa (Medicago sativa L.) showed that MsATG13 is upregulated in response to cold stress. In the present study, we found that MsATG13 transgenic tobacco enhanced cold tolerance compared to wild-type (WT) plants. Transmission electron microscopy demonstrated that transgenic tobacco overexpressing MsATG13 formed more autophagosomes than WT plants in response to cold stress conditions. The transgenic tobacco increased autophagy levels due to upregulation of other ATGs that were necessary for autophagosome production under cold stress conditions. MsATG13 transgenic tobacco also increased the proline contents and antioxidant enzyme activities, enhancing the antioxidant defense capabilities under cold stress conditions. Furthermore, MsATG13 overexpression decreased levels of superoxide anion radicals and hydrogen peroxide under cold stress conditions. These findings demonstrate the role of MsATG13 in enhancing plant cold tolerance through modulation of autophagy and antioxidant levels.

[Exploring the mechanisms of ferroptosis in non-obstructive azoospermia based on bioinformatics and machine learning].

OBJECTIVE: To explor the potential mechanisms of ferroptosis involvement in non-obstructive azoospermia based on bioinformatics and machine learning methods. METHODS: To obtain disease-related datasets and ferroptosis-related genes, we utilized the GEO database and FerrDb database, respectively. Using the R software, the disease dataset was subjected to normalization, differential analysis, and GO and KEGG enrichment analysis. The differentially expressed genes from the disease dataset were then intersected with the ferroptosis-related genes to identify common genes. Core genes were selected using three machine learning algorithms, namely LASSO, SVM-RFE, and random forest. Further analysis included exploring immune infiltration correlation, predicting target drugs, and conducting molecular docking simulations. RESULTS: The differential analysis of the GSE45885 dataset yielded 1751 differentially expressed genes, while the GSE145467 dataset yielded 4358 differentially expressed genes. The intersection of these two gene sets resulted in a disease-related gene set consisting of 508 genes. Taking the intersection of the disease-related gene set and the ferroptosis-related gene set, we obtained 17 disease-related ferroptosis genes. After machine learning-based screening, three core genes were identified: GPX4, HSF1, and KLHDC3. CONCLUSION: The mechanism underlying the involvement of ferroptosis in non-obstructive azoospermia may be linked to the downregulation of GPX4, HSF1, and KLHDC3 expression. This finding provides a basis for subsequent in-depth mechanistic and therapeutic studies.

Insertion of Hemin into Metal-Organic Frameworks: Mimicking Natural Peroxidase Microenvironment for the Rapid Ultrasensitive Detection of Uranium.

Constructing enzyme-like active sites in mimic enzyme systems is critical for achieving catalytic performances comparable to natural enzymes and can shed light on the natural development of enzymes. In this study, we described a specific hemin-based mimetic enzyme, which was facilely synthesized by the assembly of zeolitic imidazolate framework-l (ZIF-l) and hemin. The obtained hemin-based mimetic enzyme (denoted as ZIF-l-hemin) displayed enhanced peroxidase activity compared to free hemin in solution. Such excellent activity originated from the ZIF-l framework mimicking the active site cavity microenvironment of horseradish peroxidase in terms of axially coordinated histidine and distal histidine. Additionally, the constructed peroxidase mimetic was extremely resistant to a variety of severe circumstances that would normally denature natural enzymes. These characteristics made ZIF-l-hemin a potential platform for the colorimetric sensor of uranium (UO22+) with wide linear ranges (0.25-40 µM) and low limits of detection (0.079 µM). Moreover, the detection mechanism demonstrated that the coordination of uranyl ion with imidazole of ZIF-l-hemin reduced the catalytic efficiency of ZIF-l-hemin. The current work not only proposed a novel approach for fabricating artificial peroxidase but also offered facile colorimetric methods for selective radionuclide detection.

The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China.

BACKGROUND: The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. METHODS: A case-control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. RESULTS: Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose-response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). CONCLUSIONS: Perchlorate can increase the risk of PTC in a non-linear dose-response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

Room temperature fabrication of magnetic covalent organic frameworks for analyzing sulfonamide residues in animal-derived foods.

A magnetic solid phase extraction method based on magnetic covalent organic frameworks (TpBD@Fe3 O4 ; 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD)) combined with high performance liquid chromatography has been developed to detect the sulfonamides including sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole in milk and meat. TpBD@Fe3 O4 were synthesized at room temperature under mild reaction conditions with a simple and rapid operation. The TpBD@Fe3 O4 exhibited higher extraction efficiency because of the π-π and electrostatic interactions between the benzene ring structure of the TpBD and the sulfonamide molecules. The extraction conditions including the dosage of adsorbents, the type and dosage of eluent, the elution time, and the pH of the sample solution were fully optimized. The detection results showed good linearity over a wide range (50-5 × 104 ng/mL) and low detection limits (3.39-5.77 ng/mL) for the sulfonamide targets. The practicability of this magnetic solidphase extraction-high-performance liquid chromatography method was further evaluated by analyzing milk and meat samples, with recoveries of the targets of 71.6-110.8% in milk and 71.9-109.7% in pork. The successful detection of sulfonamides residues has demonstrated the TpBD@Fe3 O4 excellent practical potential for analyzing pharmaceutical residues in animal-derived foods.

Changes of retinal ganglion cell complex after vitrectomy in rhegmatogenous retinal detachment patients and its correlation with inflammatory blood biomarkers.

PURPOSE: To compare retinal ganglion cell complex (GCC) parameters between rhegmatogenous retinal detachment (RRD) eyes and normal contralateral eyes after vitrectomy and to evaluate their correlation with inflammatory blood markers. METHODS: We investigated 25 eyes that underwent vitrectomy due to RRD. Venous blood samples were collected from all participants before 08:00 a.m. on the second day of admission after a 12-hour fast for blood counts. The differences of retinal structure between RRD and contralateral eyes were compared 1 week postoperatively. RESULTS: Focal loss volume (FLV) (2.009 ± 1.286)% was significantly increased compared with the contralateral eyes (p <  0.001). Monocyte-to-high-density lipoprotein was significantly positively correlated with GCC thickness parameters, and negatively correlated with FLV and global loss volume (GLV). Postoperative best-corrected visual acuity was negatively correlated with GLV (p = 0.039, R2 = 0.172). CONCLUSION: Retinal ganglion cells (RGCs) loss might present early postoperatively in RRD eyes, and was associated with systemic inflammation. RGCs loss might affect postoperative vision.

A rare combination of cardiovascular anomaly: Aortic stenosis at sinotubular junction level and discontinuity of right coronary artery.

BACKGROUND: Supravalvular aortic stenosis (SVAS) and congenital discontinuity of right coronary artery are both rare congenital cardiovascular abnormalities. This is the first case report about SVAS that occurred with the congenital discontinuity of right coronary artery. MATERIALS & METHODS: A 3-month-old female infant presented with aortic stenosis at sinotubular level and congenital right coronary artery deficiency. According to cardiovascular CT results, Doty technique was adopted to restore the aortic root geometry under cardiopulmonary bypass. An angioplasty was performed to establish right coronary blood flow at the same time. The patient had no abnormal cardiac symptoms after surgery. The postoperative echocardiogram revealed a normal laminar flow of the right coronary artery into the right coronary sinus, normal aortic blood flow and normal myocardial functions. DISCUSSION: SVAS is characterized by the stenosis of the lumen of the ascending aorta above the aortic valve. Congenital discontinuity of RCA is probably related to dysplasia or congenital occlusion of the RCA during the development of embryo. This kind of malformation may lead to the deficiency of blood supply in sinoatrial and atrioventricular node, eventually causing their dysfunction, which usually leads to arrhythmias as the main manifestations. Angioplasty can improve blood supply of the heart without increasing the risk of major complications, and perioperative prognosis revealed good. This case image also suggested that cardiovascular CT can provide excellent visualization of complex vascular anatomies. CONCLUSIONS: We reported this rare combination of malformations consisted of SVAS and discontinuity of right coronary artery. We treated this patient with the Doty technique and angioplasty procedures.

Preparation of Nitrogen and Sulfur Co-Doped Fluorescent Carbon Dots from Cellulose Nanocrystals as a Sensor for the Detection of Rutin.

The poor water solubility, large particle size, and low accessibility of cellulose, the most abundant bioresource, have restricted its generalization to carbon dots (CDs). Herein, nitrogen and sulfur co-doped fluorescent carbon dots (N, S-CDs) were hydrothermally synthesized using cellulose nanocrystals (CNC) as a carbon precursor, exhibiting a small particle size and excellent aqueous dispersion. Thiourea was selected as a nitrogen and sulfur dopant to introduce abundant fluorescent functional groups into N, S-CDs. The resulting N, S-CDs exhibited nanoscale size (6.2 nm), abundant functional groups, bright blue fluorescence, high quantum yield (QY = 27.4%), and high overall yield (16.2%). The excellent optical properties of N, S-CDs endowed it to potentially display a highly sensitive fluorescence "turn off" response to rutin. The fluorescence response for rutin allowed a wide linear range of 0-40 mg·L-1, with a limit of detection (LOD) of 0.02 µM, which revealed the potential of N, S-CDs as a rapid and simple sensing platform for rutin detection. In addition, the sustainable and large-scale production of the N, S-CDs in this study paves the way for the successful high-value utilization of cellulose.

Fabrication of magnetic dual-hydrophilic metal organic framework for highly efficient glycopeptide enrichment.

Highly selective glycopeptide enrichment is important before mass spectrometry analysis because of the ultra-low abundance of glycopeptides in the peptide mixtures. Herein, a UiO-66-NH2-based magnetic composite was prepared and used for the hydrophilic enrichment of glycopeptides. The composite was modified with phytic acid (PA) molecules by partially replacing 2-aminoterephthalic acid ligands in UiO-66-NH2, with electrostatic interactions also promoting this modification process. Based on the hydrophilicity of both the PA molecules and the UiO-66-NH2 skeleton, the resulting material, denoted as MUiO-66-NH2/PA, showed excellent dual hydrophilicity towards glycopeptide enrichment. Compared with pure UiO-66-NH2, the specific surface area and hydrophilicity of the prepared material were increased, and MUiO-66-NH2/PA exhibited good magnetic responsiveness to facilitate a convenient enrichment procedure. HRP and IgG were used as standard proteins to evaluate the glycopeptide enrichment properties, with 21 and 34 glycopeptides enriched from their tryptic digests. Furthermore, MUiO-66-NH2/PA showed outstanding sensitivity (1 fmol/µL) and selectivity (HRP/BSA = 1:1000), and achieved remarkable glycopeptide enrichment performance for practical human serum samples. Notably, MUiO-66-NH2/PA showed perfect reusability and stability, achieving enrichment performance after five cycles similar to that of the first use. This material can be used for glycopeptide enrichment to obtain further glycosylation information, providing the possibility for cancer treatment.

Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction.

Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that possess neuroendocrine and reproductive toxicity to humans and disturb thyroid hormone homeostasis, neurobehavior, and development. The most predominant congener of PBDEs in humans and other organisms is 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); however, the molecular mechanisms underlying its cytotoxicity remain largely unknown. Here, we evaluated the toxic effect and underlying mechanism of nuclear receptors (NRs) induced by BDE-47 in SK-N-SH human neuroblastoma cells. The CCK-8 cell viability assay showed that the proliferation of human SK-N-SH cells exposed to BDE-47 was significantly inhibited in time- and dose-dependent manners, and flow cytometry showed that cell cycle was arrested at the S phase after BDE-47 exposure. Moreover, compared with the control group, the expression of retinoic acid receptor alpha (RXRα), pregnane X receptor (PXR), thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors (PPARs) at the mRNA and protein levels was significantly increased, as determined by quantitative PCR and western blot analysis, demonstrating that BDE-47 activated the NRs in vitro. Moreover, BDE-47 could bind to all four NRs in the affinity order of PPARγ > PXR > TRß > RXRα under molecular dynamics. Because RXR is the promiscuous dimerization partner for a large number of NRs, ZDock was used to calculate its interaction with other three NRs. Taking the number of hydrogen bonds and ZDock scores into account, the rank of docking ability between RXRα and the NRs was PXR > TRß > PPARγ. Further analysis of the interaction between BDE-47 and dimerized-NRs, the affinity order was RXRα > TRß > PXR > PPARγ via Glide. The results of this study demonstrated that BDE-47 interfered the cross-talk among NRs, especially the promiscuous RXRα, which might be critical for the harmonized re-adjustment of cytotoxicity and biological regulation. Our findings provide a better understanding of the mechanisms underlying toxic effects and intermolecular interaction induced by BDE-47.

A case-control study on the association of mineral elements exposure and thyroid tumor and goiter.

Thyroid tumor and thyroid goiter are prevalent disease around the world. In this case-control study, we investigated the association between exposure to a total of twelve mineral elements and thyroid disease as well as thyroid functions. Participants with thyroid tumor or goiter (N = 197) were matched with a healthy population (N = 197) by age (± 2 years old) and same sex. Questionnaires were used to collect data about the demographic characteristics and information of subjects. Serum and urine samples were collected simultaneously for each of the subjects. Mineral elements, iodine level of urine and levels of the total seven thyroid function indexes in serum were detected respectively. Conditional logistic regression was applied to estimate the associations between mineral elements and the risk of thyroid tumor and goiter through single-element models and multiple-element models. Multiple linear regression was used to evaluate relationships between mineral elements and percentage changes of thyroid functions. Higher concentrations of mineral elements in the recruited population were found in this study than other comparable studies, and the levels of chromium (Cr), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), selenium (Se), antimony (Sb), thallium (Tl) and lead (Pb) in the case group were lower than the control group. According to the single-element models, Cr, Mn, Ni, Sb and Tl showed significant negative associations with the risk of thyroid tumor and goiter, and, Cd showed nonmonotonic dose response. Cd and mercury (Hg) showed a nonmonotonic percentage change with T4, while Tl was associated with the increased FT4 in the control group. Therefore, Cd, Hg and Tl may disturb the balance of thyroid function to some extent, and Cr, Mn, Ni, Cd, Sb, and Tl may become potential influencing factors for the risk of thyroid tumor and goiter.

Controllable and high-performance immobilized enzyme reactor: DNA-directed immobilization of multienzyme in polyamidoamine dendrimer-functionalized capillaries.

In recent years, CE-integrated immobilized enzyme reactors (IMERs) for single-enzyme immobilization have attracted considerable attention. However, there has been little research on multienzyme immobilization in CE. Here, we introduce a method for fabricating a CE-integrated IMER, using DNA-directed immobilization to fix glucose oxidase and horseradish peroxidase in the capillary, which had been functionalized with polyamidoamine dendrimer (PAMAM). Owing to the reversibility of DNA hybridization, the reactor is capable of dynamic immobilization. Moreover, by introducing the PAMAM, the loading capacity of the IMER is greatly enhanced, and the PAMAM can spontaneously form complexes with DNA and then contribute to the efficiency and stability of the reactor. After 25 days storage, the prepared IMER ultimately retained approximately 70% of its initial activity. We also used the IMER to detect glucose, and the favorable linearity was obtained over the concentration range of 0.78-12.5 mM, with an LOD of 0.39 mM, demonstrating that the CE-integrated IMER can be applied to actual samples. We believe that this strategy can be extended to other multienzyme immobilization systems, and CE-integrated IMERs are potentially useful in a wide range of biochemical research applications.