ABSTRACT
Transparent, inorganic composite materials are of broad interest, from structural components in astronomical telescopes and mirror supports to solid-state lasers, smart window devices, and gravitational wave detectors. Despite great progress in material synthesis, it remains a standing challenge to fabricate such transparent glass composites with high crystallinity (HC-TGC). Here, we demonstrate the co-solidification of a mixture of melts with a stark contrast in crystallization habit as an approach for preparing HC-TGC materials. The melts used in this approach are selected so that glass formation and crystal precipitation occur simultaneously and synergistically, avoiding the formation of interfacial cracks, residual pores, and delamination effects. Using this method, various unusual hybridized HC-TGC materials such as oxychloride, oxybromide, and oxyiodide composite systems were fabricated in dense, bulk shapes. These materials exhibit intriguing optical properties and neutron response-ability. Using such HC-TGC materials, we develop a neutron detector and demonstrate the application for efficient neutron monitoring and even single neutron detection. We expect that these findings may help to bring about a generation of fully inorganic, transparent composites with synergistic combinations of conventionally incompatible materials.
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We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.
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1,4-Dimethylphenazine endoperoxide releases singlet oxygen with a half-life of 89 hours at 37 °C. The thermal cycloreversion reaction is accompanied by a strong increase in the emission intensity with a peak at 490 nm, due to the formation of the phenazine core. The endoperoxide is effective against cancer cells in culture medium and tumor spheroids, with singlet oxygen-mediated cytotoxicity.
Subject(s)
Phenazines , Singlet Oxygen , Singlet Oxygen/metabolism , Singlet Oxygen/chemistry , Humans , Phenazines/chemistry , Phenazines/pharmacology , Cell Survival/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Molecular StructureABSTRACT
The clinical practice of photodynamic therapy of cancer (PDT) is mostly limited to superficial types of skin cancer. The major reason behind this limited applicability is the need for light in the photogeneration of ROS, and in particular singlet oxygen. In order to circumvent this major roadblock, we designed and synthesized naphthalene-derived endoperoxides with mitochondria targeting triphenylphosphonium moieties. Here, we show that these compounds release singlet oxygen by thermal cycloreversion, and initiate cell death with IC50 < 10 µM in cancer cell cultures. The mouse 4T1 breast tumor model study, where the endoperoxide compound was introduced intraperitoneally, also showed highly promising results, with negligible systemic toxicity. Targeted delivery of singlet oxygen to cancer cell mitochondria could be the breakthrough needed to transform Photodynamic Therapy into a broadly applicable methodology for cancer treatment by keeping the central tenet and discarding problematic dependencies on oxygen or external light.
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Objectives: To establish a novel deep learning networks (MSF-MPTnet) based on panoramic radiographs (PRs) for automatic assessment of relationship between maxillary sinus floor (MSF) and maxillary posterior teeth (MPT), and to compare accuracy of MSF-MPTnet, dentists and radiologists identifying contact relationship. Study design: A total of 1035 PRs and 1035 Cone-beam computed tomographys ï¼CBCTï¼images were collected from January 2018 to April 2022. The relationships were classified into class I and II by CBCT. Class I represents non-contact group, and class II represents contact group. 350 PRs were randomly selected as test dataset and accuracy of MSF-MPTnet, dentists, and radiologists was compared. Results: The intraclass correlation coefficient of dentists was 0.460-0.690 and it was 0.453-0.664 for radiologists. Sensitivity and accuracy of MSF-MPTnet were 0.682-0.852and 0.890-0.951, indicating that the output performance of MSF-MPTnet was reliable. Accuracy of maxillary premolars and molars were 79.7%-90.3 %, 76.2%-89.2 % and 72.9%-88.3 % in MSF-MPTnet model, dentists and radiologists. Accuracy of class I relationship in the MSF-MPTnet model (67.7%-94.6 %) was higher than that of dentists (56.5%-84.6 %) in maxillary first premolars and right second premolar, and accuracy of class I relationship in the MSF-MPTnet model is also higher than radiologists (40.0%-78.1 %) in all teeth positions (p < 0.05). Conclusions: MSF-MPTnet model could increase detecting accuracy of the relationship between MSF and MPT, minimize pseudo contact relationship and reduce frequency of CBCT use.
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In this paper, a temperature measurement system with NTC (Negative Temperature Coefficient) thermistors was designed. An MCU (Micro Control Unit) primarily operates by converting the voltage value collected by an ADC (Analog-to-Digital Converter) into the resistance value. The temperature value is then calculated, and a DAC (Digital-to-Analog Converter) outputs a current of 4 to 20 mA that is linearly related to the temperature value. The nonlinear characteristics of NTC thermistors pose a challenging problem. The nonlinear characteristics of NTC thermistors were to a great extent solved by using a resistance ratio model. The high precision of the NTC thermistor is obtained by fitting it with the Hoge equation. The results of actual measurements suggest that each module works properly, and the temperature measurement accuracy of 0.067 °C in the range from -40 °C to 120 °C has been achieved. The uncertainty of the output current is analyzed and calculated with the uncertainty of 0.0014 mA. This type of system has broad potential applications in industry fields such as the petrochemical industry.
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Periampullary cancer is a malignant tumor occurring around the ampullary region of the liver and pancreas, encompassing a variety of tissue types and sharing numerous biological characteristics, including interactions with the nervous system. The nervous system plays a crucial role in regulating organ development, maintaining physiological equilibrium, and ensuring life process plasticity, a role that is equally pivotal in oncology. Investigations into nerve-tumor interactions have unveiled their key part in controlling cancer progression, inhibiting anti-tumor immune responses, facilitating invasion and metastasis, and triggering neuropathic pain. Despite many mechanisms by which nerve fibers contribute to cancer advancement still being incompletely understood, the growing emphasis on the significance of nerves within the tumor microenvironment in recent years has set the stage for the development of groundbreaking therapies. This includes combining current neuroactive medications with established therapeutic protocols. This review centers on the mechanisms of Periampullary cancer's interactions with nerves, the influence of various types of nerve innervation on cancer evolution, and outlines the horizons for ongoing and forthcoming research.
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BACKGROUND: This study aims to investigate the incidence and dynamic risk factors for cardiovascular diseases (CVD) among people living with HIV (PLWH). METHODS: In this population-based statewide cohort study, we utilized integrated electronic health records data to identify adult (age ≥ 18) who were diagnosed with HIV between 2006 and 2019 and were CVD event-free at the HIV diagnosis in South Carolina. The associations of HIV-related factors and traditional risk factors with the CVD incidence were investigated during the overall study period, and by different follow-up periods (i.e., 0-5yrs, 6-10yrs 11-15yrs) using multivariable logistic regression models. RESULTS: Among 9,082 eligible participants, the incidence of CVD was 18.64 cases per 1000 person-years. Overall, conventional risk factors, such as tobacco use, hypertension, obesity, chronic kidney disease (CKD), were persistently associated with the outcome across all three groups. While HIV-related factors, such as recent CD4 count (e.g., > 350 vs. <200 cells/mm3: adjusted odds ratio [aOR] range: 0.18-0.25), and percent of years in retention (e.g., 31-75% vs. 0-30%: aOR range: 0.24-0.57) were associated with lower odds of CVD incidence regardless of different follow up periods. The impact of the percent of days with viral suppression gradually diminished as the follow-up period increased. CONCLUSIONS: Maintaining an optimal viral suppression might prevent CVD incidence in the short term, whereas restoring immune recovery may be beneficial for reducing CVD risk regardless of the duration of HIV diagnosis. Our findings suggest the necessity of conducting more targeted interventions during different periods of HIV infection.
Subject(s)
Cardiovascular Diseases , HIV Infections , Humans , HIV Infections/epidemiology , HIV Infections/complications , Cardiovascular Diseases/epidemiology , Male , Female , Adult , Middle Aged , Risk Factors , Incidence , South Carolina/epidemiology , Cohort Studies , Young Adult , Electronic Health Records/statistics & numerical dataABSTRACT
Plant growth and development are inhibited by the high levels of ions and pH due to soda saline-alkali soil, and the cell wall serves as a crucial barrier against external stresses in plant cells. Proteins in the cell wall play important roles in plant cell growth, morphogenesis, pathogen infection and environmental response. In the current study, the full-length coding sequence of the vegetative cell wall protein gene OsGP1 was characterized from Lj11 (Oryza sativa longjing11), it contained 660 bp nucleotides encoding 219 amino acids. Protein-protein interaction network analysis revealed possible interaction between CESA1, TUBB8, and OsJ_01535 proteins, which are related to plant growth and cell wall synthesis. OsGP1 was found to be localized in the cell membrane and cell wall. Furthermore, overexpression of OsGP1 leads to increase in plant height and fresh weight, showing enhanced resistance to saline-alkali stress. The ROS (reactive oxygen species) scavengers were regulated by OsGP1 protein, peroxidase and superoxide dismutase activities were significantly higher, while malondialdehyde was lower in the overexpression line under stress. These results suggest that OsGP1 improves saline-alkali stress tolerance of rice possibly through cell wall-mediated intracellular environmental homeostasis.
Subject(s)
Oryza , Oryza/genetics , Cell Wall , Cell Membrane , Peroxidase , AlkaliesABSTRACT
The resolving power of metalens telescopes rely on their aperture size. Flat telescopes are advancing with the research on super-resolution confocal metalenses with large aperture. However, the aperture sizes of metalenses are usually bound within hundreds of micrometers due to computational and fabrication challenges, limiting their usage on practical optical devices like telescopes. In this work, we demonstrated a two-step designing method for the design of dual-band far-field super-resolution metalens with aperture sizes from the micro-scale to macro-scale. By utilizing two types of inserted unit cells, the phase profile of a dual-wavelength metalens with a small aperture of 100 µm was constructed. Through numerical simulation, the measured FWHM values of the focal spots of 5.81 µm and 6.81 µm at working wavelengths of 632.8 nm and 1265.6 nm were found to all be slightly smaller than the values of 0.61 λ/NA, demonstrating the super-resolution imaging of the designed metalens. By measuring the optical power ratio of the focal plane and the incident plane, the focusing efficiencies were 76% at 632.8 nm and 64% at 1265.6 nm. Based on the design method for small-aperture metalens, far-field imaging properties through the macro metalens with an aperture of 40 mm were simulated by using the Huygens-Fresnel principle. The simulation results demonstrate confocal far-field imaging behavior at the target wavelengths of 632.8 nm and 1265.6 nm, with a focal length of 200 mm. The design method for dual-band far-field super-resolution metalens with a large aperture opens a door towards the practical applications in the dual-band space telescope system.
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Purpose: Early-stage lung cancer is typically characterized clinically by the presence of isolated lung nodules. Thousands of cases are examined each year, and one case usually contains numerous lung CT slices. Detecting and classifying early microscopic lung nodules is demanding due to their diminutive dimensions and restricted characterization capabilities. Therefore, a lung nodule classification model that performs well and is sensitive to microscopic lung nodules is needed to accurately classify lung nodules. Methods: This paper uses the Resnet34 network as a basic classification model. A new cascade lung nodule classification method is proposed to classify lung nodules into 6 classes instead of the traditional 2 or 4 classes. It can effectively classify six different nodule types including ground-glass and solid nodules, benign and malignant nodules, and nodules with predominantly ground-glass or solid components. Results: In this paper, the traditional multi-classification method and the cascade classification method proposed in this paper were tested using real lung nodule data collected in the clinic. The test results demonstrate that the cascade classification method in this study achieves an accuracy of 80.04%, outperforming the conventional multi-classification approach. Conclusions: Different from the existing methods for categorizing the benign and malignant nature of lung nodules, the approach presented in this paper can classify lung nodules into 6 categories more accurately. At the same time, This paper proposes a rapid, precise, and dependable approach for classifying six distinct categories of lung nodules, which increases the accuracy categorization compared with the traditional multivariate categorization method.
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OBJECTIVES: This study aimed to provide a universal and reliable reference system quantifying temporomandibular joint (TMJ) morphological and positional changes. METHODS: Large field-of-view (FOV) cone-beam computed tomography (CBCT) images (20 TMJs) from 10 preorthognathic surgery patients and limited FOV CBCT images (40 TMJs) from 20 splint therapy-treated patients with temporomandibular disorders were collected. TMJ-specific reference system including a TMJ horizontal reference plane (TMJHP) and a local coordinate system (TMJCS) was constructed with landmarks on cranial base. Its application for TMJ measurements and its spatial relationship to common Frankfort horizontal plane (FHP) and maxillofacial coordinate system (MFCS) were evaluated. RESULTS: Five relevant landmarks were selected to optimally construct TMJ-specific reference system. General parallelism between TMJHP and FHP was demonstrated by minimal angular and constant distance deviation (1.714â ±â 0.811º; 2.925â ±â 0.817 mm). Additionally, tiny axial orientational deviations (0.181â ±â 6.805º) suggested TMJCS rivaled MFCS. Moreover, small deviations in orientations and distances (1.232â ±â 0.609º; 0.310â ±â 0.202 mm) indicated considerable reliability for TMJCS construction, with intraclass correlation coefficients (ICCs) ranging from 0.999 to 1.000. Lastly, slight discrepancies in translations and rotations revealed high reliability for condylar positional and morphological measurements (ICC, 0.918-0.999). LIMITATIONS: TMJ-specific reference system was merely tested in two representative FOVs. CONCLUSIONS: This study provides a universal and reliable reference system for TMJ assessment that is applicable to both limited and large FOV CBCT. It would improve comparability among diverse studies and enable comprehensive evaluations of TMJ positional and morphological changes during TMJ-related treatment follow-up such as splint therapy and disease progression.
Subject(s)
Mandibular Condyle , Temporomandibular Joint Disorders , Humans , Mandibular Condyle/diagnostic imaging , Reproducibility of Results , Temporomandibular Joint/diagnostic imaging , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint Disorders/therapy , Cone-Beam Computed Tomography/methodsABSTRACT
Aqueous Ca-ion batteries (ACIBs) attract immense attention due to its high safety and the high abundance of calcium. However, the development of ACIBs is hindered by the lack of high voltage cathode materials to host the large radius and divalent Ca2+ . Herein, polyanionic phosphate K3 V2 (PO4 )3 /C (KVP/C) is provided as a new cathode material for ACIBs. Due to the robust structure of polyanion material and the wide electrochemical window of water-in-salt electrolyte, KVP/C delivers a high working voltage of 3.74 V versus Ca2+ /Ca with a specific capacity of 102.4 mAh g-1 and a long-life of 6000 cycles at 500 mA g-1 . Furthermore, the calcium storage mechanism of KVP/C is shown to be the coexistence of solid solution and two-phase reaction by in situ X-ray diffraction, ex situ transmission electron microscope, and X-ray photoelectron spectroscopy. Finally, an aqueous calcium-ion full cell, based on an organic compound as anode and KVP/C as cathode, is constructed and it shows good stability for 200 cycles and a specific capacity of 80.2 mAh g-1 . This work demonstrates that vanadium-based phosphate materials are promising high-voltage cathode materials for ACIBs and renew the prospects for ACIBs.
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Substituting the sluggish oxygen evolution reaction with the sulfur oxidation reaction can significantly reduce energy consumption and eliminate environmental pollutants during hydrogen generation. However, the progress of this technology has been hindered due to the lack of cost-effective, efficient, and durable electrocatalysts. In this study, we present the design and construction of a hierarchical metal sulfide catalyst with a gradient structure comprising nanoparticles, nanosheets, and microparticles. This was achieved through a structure-breaking sulfuration strategy, resulting in a "ball of yarn"-like core/shell CoS/MoS2 microflower with CoS/MoS2/CoS dual-heterojunctions. The difference in work functions between CoS and MoS2 induces an electron polarization effect, creating dual built-in electric fields at the hierarchical interfaces. This effectively modulates the adsorption behavior of catalytic intermediates, thereby reducing the energy barrier for catalytic reactions. The optimized catalyst exhibits outstanding electrocatalytic performance for both the hydrogen evolution reaction and the sulfur oxidation reaction. Remarkably, in the assembled electrocatalytic coupling system, it only requires a cell voltage of 0.528 V at 10 mA cm-2 and maintains long-term durability for over 168 h. This work presents new opportunities for low-cost hydrogen production and environmentally friendly sulfion recycling.
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OBJECTIVES: This study aims to characterize and compare COVID-19 breakthrough infections between people living with and without HIV across different phases of the pandemic. METHODS: Using statewide HIV cohort data, the study population included adult residents in South Carolina (SC) (>18 years old) who were fully vaccinated between January 02, 2021 and April 14, 2022 when Alpha, Delta, and Omicron variants were circulating in SC. We used the Cox proportional hazard model to investigate the association between HIV infection and breakthrough infection, adjusting for relevant covariates. RESULTS: Among 2,144,415 vaccinated individuals, 8,335 were people living with HIV (PLWH) and 2,136,080 were people without HIV (PWoH). After propensity score matching, HIV infection was not significantly associated with breakthrough infection rate. However, when comparing breakthrough infections among individuals without any booster dose, PLWH had a higher risk of breakthrough infections (adjusted Hazard Ration: 1.19; 95% confidence interval: 1.03-1.39). Compared to PWoH, PLWH with high levels of clusters of differentiation 4 (CD4) count or viral suppression were not associated with breakthrough infections. CONCLUSIONS: Our findings do not support a broad conclusion that COVID-19 vaccine effectiveness is lower among PLWH, while we did find that PLWH had a higher risk of breakthrough infection compared to PWoH if they did not receive a booster dose.
Subject(s)
COVID-19 , HIV Infections , Adult , Humans , Adolescent , COVID-19/epidemiology , Breakthrough Infections , COVID-19 Vaccines , HIV Infections/complications , HIV Infections/epidemiology , SARS-CoV-2ABSTRACT
Fluid resuscitation is an important way in the treatment of acute pancreatitis (AP). This meta-analysis aimed to compare the safety and efficacy of Lactate Ringer's solution (LR) and Normal Saline (NS) in the treatment of patients with acute pancreatitis. Searched in PubMed, Web of Science Core Collection (Clarivate), Embase, Cochrane Library, CNKI, China Wanfang, and China VIP database. All randomized controlled clinical trials (RCTs) were identified. Six studies with 431 patients were included. Compared with NS, LR can significantly reduce the incidence of SIRS at 24h, reduce the length of hospitalization, moderate-severe AP, ICU admission and local complications, especially pancreatic necrosis. It is safe and effective to choose LR for fluid resuscitation in AP, but due to the small number of included studies, multi-center and large-sample RCTs are still needed for further verification. PROSPERO registration number: CRD42022322788.
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AIMS: Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others. METHODS: We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed. RESULTS: This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I2 = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I2 = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I2 = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I2 = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I2 = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I2 = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes. CONCLUSIONS: SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount. REGISTRATION: Prospero CRD42023408276.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Hypoglycemia , Sodium-Glucose Transporter 2 Inhibitors , Humans , Insulin/adverse effects , Hypoglycemic Agents/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Insulin, Regular, Human/therapeutic use , Diabetic Ketoacidosis/chemically induced , Diabetic Ketoacidosis/epidemiology , Diabetic Ketoacidosis/prevention & control , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Hypoglycemia/prevention & control , Glucose , Sodium , Randomized Controlled Trials as TopicABSTRACT
The orange subfamily (Aurantioideae) contains several Citrus species cultivated worldwide, such as sweet orange and lemon. The origin of Citrus species has long been debated and less is known about the Aurantioideae. Here, we compiled the genome sequences of 314 accessions, de novo assembled the genomes of 12 species and constructed a graph-based pangenome for Aurantioideae. Our analysis indicates that the ancient Indian Plate is the ancestral area for Citrus-related genera and that South Central China is the primary center of origin of the Citrus genus. We found substantial variations in the sequence and expression of the PH4 gene in Citrus relative to Citrus-related genera. Gene editing and biochemical experiments demonstrate a central role for PH4 in the accumulation of citric acid in citrus fruits. This study provides insights into the origin and evolution of the orange subfamily and a regulatory mechanism underpinning the evolution of fruit taste.
Subject(s)
Citrus sinensis , Citrus , Citrus/genetics , Citrus/metabolism , Citrus sinensis/genetics , Citrus sinensis/metabolism , Citric Acid/metabolism , Fruit/genetics , ChinaABSTRACT
Photoaffinity labeling (PAL) has blossomed into a powerful and versatile tool for capture and identification of biomolecular targets. However, low labeling efficiency for specific targets such as lectins, the tedious process for protein purification, inevitable cellular photodamage, and less tissue penetration of UV light are significant challenges. Herein, we reported a near-infrared (NIR) light-driven photoaffinity labeling approach using upconverting nanoparticle (UCNP)-based photoactive probes, which were constructed by assembling photoactive groups and ligands onto NaYF4:Yb,Tm nanoparticles. The novel probes were easily prepared and functionalized, and the labeled proteins can be isolated and purified through simple centrifugation and washing. The advantages of this approach were demonstrated by labeling and isolation of peanut agglutinin (PNA), asialoglycoprotein receptor (ASGPR), and human carbonic anhydrase II (hCAII) from mixed proteins or cell lysates with good selectivity and efficiency, especially for PNA and ASGPR, two lectins that showed low binding affinity to their ligands. More importantly, successful labeling of PNA through pork tissues and ASGPR in mice strongly proved the good tissue penetrating capacity of NIR light and the application potential of UCNP-based photoactive probes for protein labeling in vivo. Biosafety of this approach was experimentally validated by enzyme, cell, and animal work, and we demonstrated that NIR light caused minimal photodamage to enzyme activity compared to UV light, and the UCNP-based photoactive probe presents good biosafety both in vitro and in vivo. We believe that this novel PAL approach will provide a promising tool for study of ligand-protein interactions and identification of biomolecular targets.
Subject(s)
Nanoparticles , Ultraviolet Rays , Mice , Animals , Humans , Ligands , Lectins , Peanut Agglutinin , Nanoparticles/chemistryABSTRACT
BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.