Evaluation of the relationship between the real-time changes of macular structure and visual function in patients with rhegmatogenous retinal detachment after silicone oil tamponade.

PURPOSE: To evaluate the relationship between the real-time changes of macular structure and visual function in rhegmatogenous retinal detachment (RRD) patients. METHODS: Forty-six patients were enrolled in this retrospective study. The best corrected visual acuity (BCVA) and macular structural changes were analyzed within 3 months after silicone oil tamponade. RESULTS: The mean final BCVA was significantly better than the preoperative BCVA (P = 0.002). The parafoveal thickness became thinner, the proportion of subretinal fluid (SRF) decreased, and the proportion of intact external limiting membrane (ELM) increased within 3 months postoperatively. The recovery stage and the integrity of ELM in the SRF (-) group were significantly faster than that in the SRF (+) group (all P < 0.05). The central foveal thickness (CFT), the inferior and temporal thickness of the parafovea, and the integrity of the ELM were significantly correlated with BCVA at each time point (all P < 0.05). Long duration of preoperative RRD, thinner CFT at 1 month postoperatively, and without integrity of ELM at 3 months postoperatively were associated with poor final BCVA recovery (R2 = 0.462). CONCLUSIONS: The macular microstructural tended to restore integrity within 3 months. The presence of SRF in macula delayed the recovery of RRD patients but did not affect the visual function.

Fibroblast growth factor 20 ameliorates cardiac hypertrophy via activation ErbB2.

Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family and involved in embryonic development and cardiac repair. This study aimed to explore the role of FGF20 in cardiac hypertrophy and the underlying molecular mechanisms. FGF20 improved cardiac hypertrophy in vivo and in vitro. Furthermore, FGF20 increased expression of erythroblastic leukemia viral oncogene homolog 2 (ErbB2), which was negatively correlated with expression of the cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In addition, FGF20 effectively protected cardiomyocytes against apoptosis and oxidative stress. To further investigate whether protective effect of FGF20 is mediated by ErbB2, neonatal rat cardiomyocytes (NRCMs) were treated with lapatinib, an inhibitor of ErbB2. Lapatinib largely abrogated the anti-hypertrophic effect of FGF20, accompanied by increases in cardiomyocyte apoptosis and oxidative stress. In summary, this study reveals that FGF20 prevents cardiac hypertrophy by inhibiting apoptosis and oxidative stress via activating ErbB2 and may be a promising therapeutic strategy for cardiac hypertrophy.

Identification of serum metabolites associated with polybrominated diphenyl ethers (PBDEs) exposure in papillary thyroid carcinoma: a case-control study.

As the most common endocrine cancer, thyroid cancer (TC) has sharply increased globally over the past three decades. The growing incidence of TC might be counted by genetics, radiation, iodine, autoimmune disease, and exposure to environmental endocrine-disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs), being typical EDCs, have been widely utilized in plastics, electronics, furniture, and textiles as flame retardants since the 1980s, and research has indicated a significant correlation between their exposure and the risk of TC. Even so, PBDEs exposure impact on the metabolic signature for TC remains unexplored. In this study, eight congeners of PBDEs were determined in serum from 111 patents with papillary thyroid cancer (PTC) and 111 healthy participants based on case-control epidemiology using gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (GC-APCI-MS/MS). Based on the tertile distribution of total PBDEs concentrations in 59 participants, metabolomics analysis was further performed by ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap MS. In the partial correlation analysis, the 29 identified metabolites were correlated with PBDEs exposure (P < 0.05). In addition, PBDEs disrupted the metabolism of glycerophospholipids, sphingolipids, taurine, and hypotaurine, indicating that neurotransmitters, oxidative stress, and inflammation are the vulnerable pathways affected in PTC. Furthermore, (±)-octopamine and 5-hydroxyindole, both of which modulate the actions of neurotransmitters, emerged as potential disturbed metabolite markers for TC following exposure to PBDEs. This study analyzed the impact of PBDEs on PTC in terms of the metabolic changes and further explored possible biomarkers, which helped us have a deep understanding of the possible mechanism of the effects of PBDEs on TC.

Two-Photon Absorption Aggregation-Induced Emission Luminogen/Paclitaxel Nanoparticles for Cancer Theranostics.

Multifaceted nanoplatforms integrating fluorescence imaging and chemotherapy have garnered acknowledgment for their potential potency in cancer diagnosis and simultaneous in situ therapy. However, some drawbacks remain for traditional organic photosensitizers, such as poor photostability, short excitation wavelength, and shallow penetration depth, which will greatly lower the chemotherapy treatment efficiency. Herein, we present lipid-encapsulated two-photon active aggregation-induced emission (AIE) luminogen and paclitaxel (PTX) nanoparticles (AIE@PTX NPs) with bright red fluorescence emission, excellent photostability, and good biocompatibility. The AIE@PTX NPs exhibit dual functionality as two-photon probes for visualizing blood vessels and tumor structures, achieving penetration depth up to 186 and 120 µm, respectively. Furthermore, the tumor growth of the HeLa-xenograft model can be effectively prohibited after the fluorescence imaging-guided and PTX-induced chemotherapy, which shows great potential in the clinical application of two-photon cell and tumor fluorescence imaging and cancer treatment.

Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA.

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

Comprehensive Analysis of Penicillium Sclerotiorum: Biology, Secondary Metabolites, and Bioactive Compound Potential─A Review.

The filamentous fungus Penicillium sclerotiorum is significant in ecological and industrial domains due to its vast supply of secondary metabolites that have a diverse array of biological functions. We have gathered the metabolic potential and biological activities associated with P. sclerotiorum metabolites of various structures, based on extensive research of the latest literature. The review incorporated literature spanning from 2000 to 2023, drawing from reputable databases including Google Scholar, ScienceDirect, Scopus, and PubMed, among others. Ranging from azaphilones, meroterpenoids, polyketides, and peptides group exhibits fascinating potential pharmacological activities such as antimicrobial, anti-inflammatory, and antitumor effects, holding promise in pharmaceutical and industrial sectors. Additionally, P. sclerotiorum showcases biotechnological potential through the production of enzymes like ß-xylosidases, ß-d-glucosidase, and xylanases, pivotal in various industrial processes. This review underscores the need for further exploration into its genetic foundations and cultivation conditions to optimize the yield of valuable compounds and enzymes, highlighting the unexplored potential of P. sclerotiorum in diverse applications across industries.

Determination of [Glu1]-fibrinopeptide B purity by gas chromatography - isotope dilution mass spectrometry.

The present work assessed the purity of [Glu1]-fibrinopeptide B (GFB) as a model peptide using gas chromatography - isotope dilution mass spectrometry. GFB and various isotope-labeled amino acids were hydrolyzed in HCl and then derivatized using optimized procedures. The primary impurity in GFB was also identified and used to correct the final result. A method repeatability of 0.5% was achieved and linear calibrations were obtained for five amino acids. The LOD and LOQ were 0.041 to 0.096 µg g-1, and 0.16 to 0.56 µg g-1, respectively. The purity of GFB was found to be (0.715 ± 0.012) g g-1. This technique exhibited comparable accuracy to that obtainable from liquid chromatography - isotope dilution mass spectrometry but at lower cost. This method could be employed as a reference technique or in fields such as clinical diagnostics or bio-pharmaceutical peptide purity analysis.

Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.

Metabolic reprogramming is an adaptive response of tumour cells under hypoxia and low nutrition conditions. There is increasing evidence that glucose metabolism reprogramming can regulate the growth and metastasis of osteosarcoma (OS). Reprogramming in the progress of OS can bring opportunities for early diagnosis and treatment of OS. Previous research mainly focused on the glycolytic pathway of glucose metabolism, often neglecting the tricarboxylic acid cycle and pentose phosphate pathway. However, the tricarboxylic acid cycle and pentose phosphate pathway of glucose metabolism are also involved in the progression of OS and are closely related to this disease. The research on glucose metabolism in OS has not yet been summarized. In this review, we discuss the abnormal expression of key molecules related to glucose metabolism in OS and summarize the glucose metabolism related signaling pathways involved in the occurrence and development of OS. In addition, we discuss some of the targeted drugs that regulate glucose metabolism pathways, which can lead to effective strategies for targeted treatment of OS.

Dual-functionalized two-dimensional metal-organic framework composite with highly hydrophilicity for effective enrichment of glycopeptides.

Protein glycosylation research is currently focused on the development of various functionalized materials that can effectively enrich the levels of glycopeptides in samples. However, most of these materials possess limited glycopeptide-specific recognition sites because of large steric hindrance, unsuitable mass transfer kinetics, and relatively low surface areas. Herein, a highly hydrophilic two-dimensional (2-D) metal-organic framework (MOF) nanosheet modified with glutathione (GSH) and l-cysteine (l-Cys) (denoted as Zr-Fc MOF@Au@GC) has been synthesized for efficient glycopeptide enrichment. Using this composite material, 39 and 44 glycopeptides from horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG) digests were detected, respectively, which represents a higher efficiency for glycopeptide enrichment from model glycoprotein digests than has been previously reported. The material Zr-Fc MOF@Au@GC exhibited ultra-high sensitivity (0.1 fmol/µL), excellent selectivity (weight ratio of HRP tryptic digest to bovine serum albumin (BSA) tryptic digest = 1:2000), good binding capacity (200 mg/g), satisfactory reusability, and long-term storage capacity. In addition, 655 glycopeptides corresponding to 366 glycoproteins were identified from human serum samples. To the best of our knowledge, this is the largest number of glycoproteins detected in human serum samples to date. These results indicated that Zr-Fc MOF@Au@GC has the potential to be used for the enrichment of glycopeptides in biological samples and the analysis of protein glycosylation.

New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a form of iron-driven cell death. Mitophagy is a type of selective autophagy, where degradation of damaged mitochondria is the key mechanism for maintaining mitochondrial homeostasis. Additionally, Chaperone-mediated autophagy (CMA) is a biological process that transports individual cytoplasmic proteins to lysosomes for degradation through companion molecules such as heat shock proteins. Research has demonstrated the involvement of ferroptosis, mitophagy, and CMA in the pathological progression of Osteoarthritis (OA). Furthermore, research has indicated a significant correlation between alterations in the expression of reactive oxygen species (ROS), adenosine monophosphate (AMP)-activated protein kinase (AMPK), and hypoxia-inducible factors (HIFs) and the occurrence of OA, particularly in relation to ferroptosis and mitophagy. In light of these findings, our study aims to assess the regulatory functions of ferroptosis and mitophagy/CMA in the pathogenesis of OA. Additionally, we propose a mechanism of crosstalk between ferroptosis and mitophagy, while also examining potential pharmacological interventions for targeted therapy in OA. Ultimately, our research endeavors to offer novel insights and directions for the prevention and treatment of OA.

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide.

Photodynamic therapy based on fluorescence illumination of subcellular organelles and in situ bursts of reactive oxygen species (ROS) has been recognized as a promising strategy for cancer theranostics. However, the short life of ROS and unclarified anticancer mechanism seriously restrict the application. Herein, we rationally designed and facilely synthesized a 2,6-dimethylpyridine-based triphenylamine (TPA) derivative TPA-DMPy with aggregation-induced emission (AIE) features and production of type-I ROS. Except for its selective binding to the endoplasmic reticulum (ER), TPA-DMPy, in synergy with glibenclamide, a medicinal agent used against diabetes, induced significant apoptosis of cancer cells in vitro and in vivo. Additionally, TPA-DMPy greatly incited the release of calcium from ER upon light irradiation to further aggravate the depolarization of ER membrane potential caused by glibenclamide, thus inducing fatal ER stress and crosstalk between ER and mitochondria. Our study extends the biological design and application of AIE luminogens and provides new insights into discovering novel anticancer targets and agents.

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.

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.

Machine learning-aided metallomic profiling in serum and urine of thyroid cancer patients and its environmental implications.

The incidence rate of thyroid cancer has been growing worldwide. Thyroid health is closely related with multiple trace metals, and the nutrients are essential in maintaining thyroid function while the contaminants can disturb thyroid morphology and homeostasis. In this study, we conducted metallomic analysis in thyroid cancer patients (n = 40) and control subjects (n = 40) recruited in Shenzhen, China with a high incidence of thyroid cancer. We found significant alterations in serumal and urinary metallomic profiling (including Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, I, Ba, Tl, and Pb) and elemental correlative patterns between thyroid cancer patients and controls. Additionally, we also measured the serum Cu isotopic composition and found a multifaceted disturbance in Cu metabolism in thyroid disease patients. Based on the metallome variations, we built and assessed the thyroid cancer-predictive performance of seven machine learning algorithms. Among them, the Random Forest model performed the best with the accuracy of 1.000, 0.858, and 0.813 on the training, 5-fold cross-validation, and test set, respectively. The high performance of machine learning has demonstrated the great promise of metallomic analysis in the identification of thyroid cancer. Then, the Shapley Additive exPlanations approach was used to further interpret the variable contributions of the model and it showed that serum Pb contributed the most in the identification process. To the best of our knowledge, this is the first study that combines machine learning and metallome data for cancer identification, and it supports the indication of environmental heavy metal-related thyroid cancer etiology.

20S-Protopanaxatriol improves cognitive function of Alzheimer's disease by promoting endogenous neurogenesis.

Neurogenesis in Alzheimer's disease (AD) is impaired, and thus promoting neurogenesis is a promising strategy for treating AD-related cognition impairment. Here, we found that 20S-protopanaxatriol (PPT) can alleviate cognitive deficits in an AlCl3-induced AD zebrafish model in Y and T maze tests and increase the HUC expression of the telencephalon. PPT promotes neural stem cell (NSC) line differentiation into neurons under AD condition. PPT significantly alleviated the apoptosis and cell cycle arrest of NSCs induced by amyloid-beta. Next, we investigated the molecular mechanism of PPT in treating AD by network pharmacology and molecular docking. PPT could target PIK3CA and PI3K/AKT signaling pathways. PPT significantly reversed the reduced expression level of PIK3CA (PI3K p110), p-PI3Kp85 and p-AKT of NSCs under AD condition. These results suggested that PPT alleviated the cognitive dysfunction of AD and promoted NSC proliferation and neurogenesis through the PI3K/AKT pathway. Therefore, PPT might be a potential candidate to treat AD-related cognitive decline via enhancing endogenous neurogenesis.

Glutathione functionalized magnetic covalent organic frameworks with dual-hydrophilicity for highly efficient and selective enrichment of glycopeptides.

Glycoproteins can be used as biomarkers to detect many diseases. Reliable and efficient sample materials are essential to separate and enrich glycopeptides before detection and analysis. In this report, glutathione (GSH)-modified magnetic covalent organic framework (TpBD) composite Fe3O4@TpBD@Au@GSH was synthesized by a two-step, post-synthesis modification strategy. The native hydrophilic TpBD and the highly hydrophilic GSH furnished the composite with dual-hydrophilic performance that was superior to covalent organic framework-based materials reported previously. The composite material showed excellent performance in enriching glycopeptides from protein standards because of its superior hydrophilicity, with 21 and 36 glycopeptides enriched from horseradish peroxidase (HRP) and immunoglobulin G from human serum (IgG) tryptic digests, respectively. The prepared composite exhibited ultra-high sensitivity (0.1 fmol/µL), excellent selectivity (HRP tryptic digest/bovine serum albumin (BSA) tryptic digest = 1:2000) and macromolecular protein anti-interference ability (HRP tryptic digest/BSA = 1:2000). Moreover, Fe3O4@TpBD@Au@GSH exhibited outstanding binding capacity (160 mg/g), excellent long-term storage capacity and good recycling ability (at least six times). Glycopeptide enrichment of biological samples by Fe3O4@TpBD@Au@GSH was successful, with 492 and 160 glycopeptides, corresponding to 134 and 64 glycoproteins, detected in 5 µL human serum and human saliva samples, respectively. The results showed that Fe3O4@TpBD@Au@GSH provides more information to facilitate in-depth analysis of glycopeptides in biological samples and has broad potential in cancer monitoring and diagnosis.

Highly efficient synergistic biocatalysis driven by stably loaded enzymes within hierarchically porous iron/cobalt metal-organic framework via biomimetic mineralization.

The integration of multimodal chemo-/bio-catalysis for efficient cascade reactions has long provided broad prospects in the field of biotechnology for ages. In this work, we describe the synthesis of a biomimetic multienzyme hybrid with hierarchically porous structure and outstanding catalytic activity via in situ encapsulation of natural enzymes in an iron-cobalt bimetallic metal-organic framework (Fe/Co-MOF, FCM). The combination of a single enzyme (glucose oxidase) or dual enzyme (ß-galactosidase and glucose oxidase) with FCM resulted in remarkable synergistic biocatalysis ability; in contrast to simple biocatalyst mixtures in solution, the prepared multienzyme hybrid resulted in 3.2-fold and 2.1-fold improvements in activity for tandem reactions, respectively. The reinforced cascade bioactivity of the multienzyme hybrid benefitted from the synergistic effect between iron/cobalt in the FCM nanozyme, the opened substrate channel between enzymes/nanozymes, and the beneficial effect provided by the hierarchical MOF pores. The enlarged pores not only provided adequate space for immobilized proteins to diffuse and reorientate in FCM with low surface energy, but also reduced the intrinsic mass transfer obstacle to increase the diffusional efficiency of reactants/intermediates. In addition, on account of the shielding effect provided by FCM, the multienzyme hybrid exhibited enhanced tolerance towards severe circumstances and excellent reusability and has been successfully applied in small molecule detection, such as glucose and lactose. The current study highlights the superiority of synergistic bioreactors integrated with the MOF nanozyme and natural enzymes, suggesting great potential for applications in sustainable biomimetic catalysis.

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.

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.

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.