ABSTRACT
Multidrug resistance to clinical chemotherapeutic drugs severely limits antitumor efficacy and patient survival. The integration of chemotherapy with photothermal therapy (PTT) and reactive nitrogen species has become a major strategy to enhance cancer treatment efficacy. Herein, a multifunctional peroxynitrite (ONOO-) nanogenerator (PBT/NO/Pt) for NIR-II fluorescence (NIR-II FL)/NIR-II photoacoustic (NIR-II PA) imaging-guided chemo/NIR-II PTT/ONOO- combination therapy is reported. The multifunction nanogenerator is developed by co-loading a pH-sensitive nitric oxide donor (DETA NONOate) and nicotinamide adenine dinucleotide phosphate oxidases trigger superoxide (O2 â¢-) generator chemotherapy drug (CDDP) to an NIR-II excitation-conjugated polyelectrolyte (PNC11BA). PNC11BA has non-conjugated alkyl chain segments in the polymer backbone and abundant positively charged phenylboronic acid in its side chains, which support the anti-quenching of NIR-II FL and the integration of DETA NONOate and CDDP into PBT/NO/Pt. In the acidic tumor microenvironment, the coordination bonds between CDDP and PNC11BA are cleaved, releasing CDDP for chemotherapeutic activity. The simultaneous release of nitric oxide (NO) and O2 â¢- rapidly leads to the in situ generation of the more cytotoxic reactive physiological nitrogen species ONOO-. In vitro and in vivo results prove that PBT/NO/Pt exhibited a markedly ONOO- enhanced chemo-photothermal synergistic therapy for SKOV3/DDP tumor by downregulating the intracellular glutathione and increasing CDDP-DNA adducts.
Subject(s)
Boronic Acids , Peroxynitrous Acid , Photothermal Therapy , Peroxynitrous Acid/chemistry , Photothermal Therapy/methods , Animals , Mice , Boronic Acids/chemistry , Polyelectrolytes/chemistry , Disease Models, Animal , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, TumorABSTRACT
The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Foot , Humans , Longitudinal Studies , Diabetic Foot/diagnosis , Diabetes Mellitus, Type 2/complications , Cohort Studies , Inpatients , Glucose , Triglycerides , Blood Glucose , Risk Factors , BiomarkersABSTRACT
Enhancing the efficiency of photocatalysts in the removal of organic pollutants is of vital importance in wastewater treatment. In this work, a set of composite membranes that can be used for efficient removal of the organic dyes, such as methyl orange (MO), methylene blue (MB), and Congo red (CR), were prepared through coblending/electrospinning techniques using polyvinylidene fluoride (PVDF) as the substrate, polyvinylpyrrolidone (PVP) as the dispersing agent and wettability regulator, and cuprous oxide (Cu2O) as the photocatalyst. The results showed that Cu2O particles were well encapsulated in the electrospun PVDF/PVP fibers, and the composite membranes exhibited apparently enhanced hydrophilicity. Furthermore, compared with the pure Cu2O particles, the composite membranes not only showed a higher photocatalytic degradation ratio for MO (93.6%) but also showed a much higher degradation rate (62.4 mg/(mg·h)) in comparison with the other reported Cu2O-based composite photocatalytic materials in the literature. In addition, the membrane sample also had excellent recycling stability, and the retention rate of its removal ability maintained 92.1% after 5 times of recycling. Furthermore, the composite membranes also showed high removal ability toward MB and CR, with photocatalytic degradation ratios of 81.4 and 76.1%, respectively. This work indicates that the prepared PVDF/PVP-Cu2O composite membranes possess promising application prospects in wastewater treatment.
ABSTRACT
The ratio of red light to far-red light (R:FR) is perceived by light receptors and consequently regulates plant architecture. Regulation of shoot branching by R:FR ratio involves plant hormones. However, the roles of strigolactone (SL), the key shoot branching hormone and the interplay of different hormones in the light regulation of shoot branching in tomato (Solanum lycopersicum) are elusive. Here, we found that defects in SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and CCD8 in tomato resulted in more lateral bud growth but failed to reverse the FR inhibition of lateral bud growth, which was associated with increased auxin synthesis and decreased synthesis of cytokinin (CK) and brassinosteroid (BR). Treatment of auxin also inhibited shoot branching in ccd mutants. However, CK released the FR inhibition of lateral bud growth in ccd mutants, concomitant with the upregulation of BR synthesis genes. Furthermore, plants that overexpressed BR synthesis gene showed more lateral bud growth and the shoot branching was less sensitive to the low R:FR ratio. The results indicate that SL synthesis is dispensable for light regulation of shoot branching in tomato. Auxin mediates the response to R:FR ratio to regulate shoot branching by suppressing CK and BR synthesis.
Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Red Light , Plant Shoots/metabolism , Cytokinins , Lactones , Indoleacetic Acids , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.
ABSTRACT
Recently, growing interest in self-powered devices has led to the invention of new energy conversion devices. Photo-thermoelectric generators (PTEGs) have rapidly developed for their ability to harvest both light and thermal energy, but these devices are overly dependent on the continuity of energy input and cannot sustain output in an emergency situation. In the current study, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/graphene oxide (GO)/graphene nanosheets (GNPs)/polyethylene glycol (PEG) phase-change composites (PCCs) were prepared with freeze-drying and vacuum-filling processes to acquire materials suitable for imparting energy storage characteristics to PTEGs. The melting and crystallization enthalpies of the PCCs fabricated based on the PEDOT:PSS/GO/GNP aerogels can reach 211.5 and 207.6 J g-1, respectively, which increase by nearly 5% compared with pure PEG, and the growth rate of thermal conductivity of the composites is as high as 262.7% (1.12 W m-1 K-1). Meanwhile, the excellent photothermal properties and high-temperature shape stability that pure PEG does not possess can also be imparted to PCCs by the aerogels. The PTEG assembled with PCCs and thermoelectric components can achieve a continuous output of over 1500 s after 300 s of light irradiation. After integrating the output of the device during the lamp on/off period, it is found that the total output of the device during the light-off period (8.4 V and 9.6 mW) can far exceed its total output during the light-on period (2.7 V and 4.4 mW). This work provides guidance for modulating the performance of PCCs and giving PTEGs the ability to operate under emergency or extremely harsh conditions and the prepared PTEGs are highly promising for practical use.
ABSTRACT
The susceptibility of deep neural networks (DNNs) to adversarial intrusions, exemplified by adversarial examples, is well-documented. Conventional attacks implement unstructured, pixel-wise perturbations to mislead classifiers, which often results in a noticeable departure from natural samples and lacks human-perceptible interpretability. In this work, we present an adversarial attack strategy that implements fine-granularity, semantic-meaning-oriented structural perturbations. Our proposed methodology manipulates the semantic attributes of images through the use of disentangled latent codes. We engineer adversarial perturbations by manipulating either a single latent code or a combination thereof. To this end, we propose two unsupervised semantic manipulation strategies: one based on vector-disentangled representation and the other on feature map-disentangled representation, taking into consideration the complexity of the latent codes and the smoothness of the reconstructed images. Our empirical evaluations, conducted extensively on real-world image data, showcase the potency of our attacks, particularly against black-box classifiers. Furthermore, we establish the existence of a universal semantic adversarial example that is agnostic to specific images.
ABSTRACT
Plant architecture imposes a large impact on crop yield. IDEAL PLANT ARCHITECTURE 1 (IPA1), which encodes a SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor, is a target of molecular design for improving grain yield. However, the roles of SPL transcription factors in regulating tomato (Solanum lycopersicum) plant architecture are unclear. Here, we show that the expression of SPL13 is down-regulated in the lateral buds of strigolactone (SL)-deficient ccd mutants and is induced by GR24 (a synthetic analog of SL). Knockout of SPL13 by CRISPR/Cas9 resulted in higher levels of cytokinins (CKs) and transcripts of the CK synthesis gene ISOPENTENYL TRANSFERASES 1 (IPT1) in the stem nodes, and more growth of lateral buds. GR24 suppresses CK synthesis and lateral bud growth in ccd mutants, but is not effective in spl13 mutants. On the other hand, silencing of the IPT1 gene inhibited bud growth of spl13 mutants. Interestingly, SL levels in root extracts and exudates are significantly increased in spl13 mutants. Molecular studies indicated that SPL13 directly represses the transcription of IPT1 and the SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and MORE AXILLARY GROWTH 1 (MAX1). The results demonstrate that SPL13 acts downstream of SL to suppress lateral bud growth by inhibiting CK synthesis in tomato. Tuning the expression of SPL13 is a potential approach for decreasing the number of lateral shoots in tomato.
Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Shoots/metabolism , Gene Expression Regulation, Plant , Cytokinins/metabolism , Lactones/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Fluorescence imaging (FLI) in the near-infrared-II (NIR-II; 1000-1700 nm) window holds great potential for cancer metastasis imaging owing to its deep tissue penetration and a high signal-to-background ratio. However, currently reported organic NIR-II contrast agents generally present problems such as poor water solubility, low NIR-II fluorescence quantum yield (QY), short blood circulation half-life (t1/2), high injection doses, and undesirable tumor accumulation. In this study, an NIR-II small-molecule-based polymer (TQF-PSar) modified with four dense/hydrophilic polysarcosine (PSar) arms was prepared for efficient breast cancer pulmonary metastasis imaging. The NIR-II intensity of TQF-PSar (whose QY was calculated to be 1%) was 26.4-fold higher than that of the PEGylated nanoparticles (TQF-PEG NPs) at the same low dye dose (core TQF concentration: 2.5 µg mL-1). Moreover, owing to the ideal stealth character, TQF-PSar displayed a more prolonged blood circulation t1/2 (36.9 h) and better tumor accumulation capability than TQF-PEG NPs even at this low dye concentration. Finally, the successful use of TQF-PSar in noninvasive NIR-II FLI for breast cancer pulmonary metastasis was demonstrated in living mice.
Subject(s)
Lung Neoplasms , Nanoparticles , Animals , Mice , Peptides , Sarcosine , Optical Imaging/methods , Lung Neoplasms/diagnostic imagingABSTRACT
BACKGROUND AND AIMS: The liver plays a central role in controlling glucose and lipid metabolism. IDH2, a mitochondrial protein, controls TCA cycle flux. However, its role in regulating metabolism in obesity is still unclear. This study intends to investigate the impact of hepatic IDH2 expression on overnutrition-regulated glucose and lipid metabolism. METHODS: Hepatic IDH2 was knocked-out in mice by the approach of CRISPR-Cas9. Mice were subjected to starvation and refeeding for hepatic glucose and lipid studies in vivo. Primary hepatocytes and mouse normal liver cell line, AML12 cells were used for experiments in vitro. RESULTS: This study found that IDH2 protein levels were elevated in the livers of obese people and mice with high-fat diet consumption or hepatic steatosis. Liver IDH2-deletion mice (IDH2LKO) were resistant to high-fat diet-induced body weight gain, with lower serum glucose and TG levels, increased insulin sensitivity, and higher FGF21 secretion, despite the higher TG content in the liver. Consistently, overexpression of IDH2 in hepatocytes promoted gluconeogenesis and enhanced glycogenesis. By performing mass spectrometry and proteomics analyses, we further demonstrated that IDH2-deficiency in hepatocytes accelerated ATP production by increasing forward TCA cycle flux, thus promoting glycolysis pathway and decreasing glycogen synthesis at refeeding state, and inhibiting hepatic gluconeogenesis, increasing ß-oxidation during starvation. Moreover, experiments in vivo demonstrated that IDH2-knockout might not exacerbate hepatic inflammatory responses in the NASH model. CONCLUSIONS: Elevated hepatic IDH2 under over-nutrition state contributes to elevated gluconeogenesis and glycogen synthesis. Inhibition of IDH2 in the liver could be a potential therapeutic target for obesity and diabetes.
Subject(s)
Gluconeogenesis , Liver , Animals , Mice , Diet, High-Fat , Gluconeogenesis/genetics , Glucose/metabolism , Glycogen/metabolism , Glycolysis , Hepatocytes/metabolism , Liver/metabolism , Mice, Inbred C57BL , Obesity/genetics , Obesity/metabolismABSTRACT
Developing conjugated small molecules (CSM) with intense NIR-II (1000-1700â nm) absorption for phototheranostic is highly desirable but remains a tremendous challenge due to a lack of reliable design guidelines. This study reports a high-performance NIR-II CSM for phototheranostic by tailoring molecular planarity. A series of CSM show bathochromic absorption extended to the NIR-II region upon the increasing thiophene number, but an excessive number of thiophene results in decreased NIR-IIa (1300-1400â nm) brightness and photothermal effects. Further introduction of terminal nonconjugated alkyl chain can enhance NIR-II absorption coefficient, NIR-IIa brightness, and photothermal effects. Mechanism studies ascribe this overall enhancement to molecular planarity stemming from the collective contribution of donor/side-chain engineering. This finding directs the design of NIR-II CSM by rational manipulating molecular planarity to perform 1064â nm mediated phototheranostic at high efficiency.
ABSTRACT
Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.
Subject(s)
Reperfusion Injury , Animals , RatsABSTRACT
PURPOSE: Global longitudinal strain (GLS) seems accurate for detecting subclinical myocardial dysfunction. This study aimed to determine the association between GLS and postoperative intensity of inotropic support in the patients undergoing heart valve surgery with preserved left ventricular ejection fraction. METHODS: 74 patients with preserved left ventricular ejection fraction who underwent valve surgery during the period between March 2021 and June 2022 were included in this prospective observational study. Transthoracic echocardiography including strain analysis with speckle tracking was performed before surgery. Patients were stratified according to the left ventricle (LV) GLS: LV-GLS ≥-16% (Impaired GLS group) and LV-GLS <-16% (Normal GLS group). The primary endpoint was postoperative vasoactive inotropic score. A high vasoactive inotropic score (VIS) was defined as a maximum VIS of ≥15 within 24 hours postoperatively. Postoperative adverse events, baseline clinical and echocardiographic data were also recorded. We invested the ability of preoperative GLS in predicting adverse postoperative outcomes, such as prolonged mechanical ventilation and the need for pharmacologic hemodynamic support after cardiac surgery. RESULTS: Seventy-four patients were included and analyzed in this study, including thirty-three in impaired GLS group and forty-one in normal GLS group. In-hospital mortality was 1.27% (1/74). Patients in impaired GLS group were more likely to have prolonged mechanical ventilation (p = 0.041). Multivariable logistic regression analysis revealed that the apical four-chamber view of the left ventricle (A4C)-GLS was significantly associated with high VIS (OR 1.373, p = 0.007). A4C-GLS had a sensitivity of 62.5% and a specificity of 89.66% for predicting high VIS (area under the curve, 0.78). The relationships between GLS and other secondary outcome measures were not statistically significant. The optimal cutoff of A4C-GLS for postoperative high vasoactive inotropic score was -10.85%. CONCLUSION: Preoperative LV dysfunction is an independent risk factor for postoperative high VIS. A4C-GLS may be a reliable tool in predicting high VIS after cardiac surgery. Those patients with impaired contractility were at high risk for elevated inotropic support and prolonged mechanical ventilation after cardiac surgery. These findings suggest an important role for echocardiographic GLS in perioperative assessment of cardiac function in the patients undergoing cardiac surgery.
Subject(s)
Cardiac Surgical Procedures , Ventricular Dysfunction, Left , Humans , Ventricular Function, Left , Stroke Volume , Heart Ventricles/diagnostic imaging , Global Longitudinal Strain , Prognosis , Heart ValvesABSTRACT
Hypoxemia is 1 of the most common complications in the patients with acute Type A aortic dissection (ATAAD). This study aimed to summarize the risk factors, management strategies and long-term prognosis for postoperative hypoxemia in ATAAD patients. Baseline characteristics and clinical data of all the patients were collected. Patients were divided into 2 groups according to the PaO2/FiO2 after surgery: Hypoxemia group (nâ =â 142) and Non-hypoxemia group (nâ =â 68). The differences in gender, age, body mass index, operation time, cardiopulmonary bypass (CPB) time, aortic cross-clamping time, deep hypothermic circulatory arrest time, preoperative PaO2/FiO2, postoperative PaO2/FiO2, PaO2/FiO2 before extubating, time of mechanical ventilation, length of intensive care unit stay, length of hospital stay, in-hospital mortality, and overall mortality were compared between the 2 groups. The incidence of postoperative hypoxemia in this study was 67.6% (142/210). body mass index (26.4â ±â 3.8 vs 24.4â ±â 3.3kg/m2, Pâ <â .001) in the hypoxemia group were markedly higher and CPB time (196.3â ±â 41.0 vs 181.0â ±â 37.3 minutes, Pâ =â .010) in the hypoxemia group were significantly longer than those in the non-hypoxemia group. While preoperative PaO2/FiO2 (229.7â ±â 91.4 vs 299.7â ±â 101.2mmHg, Pâ <â .001) was significantly lower than those in the non-hypoxemia group. In the hypoxemia group, PaO2/FiO2 before extubating was significantly higher than that after operation, and the difference was significant. Logistic regression analysis showed that overweight (odds ratio [OR]: 1.113, Pâ =â .030), CPB time (OR: 1.009, Pâ =â .043) and preoperative PaO2/FiO2 (OR: 0.994, Pâ =â .001) were independent risk factors for postoperative hypoxemia. Further follow-up results showed no significant difference in long-term mortality between the 2 groups. Logistic regression analysis revealed that PaO2/FiO2 before extubating (OR: 0.985, Pâ <â .001), paraplegia (OR: 10.994, Pâ =â .019), acute renal failure (OR: 12.590, Pâ <â .001), re-operation (OR: 4.721, Pâ =â .014) and re-admission to intensive care unit (OR: 13.727, Pâ =â .001) were independent risk factors for long-term mortality. Our results showed that overweight and prolonged CPB time were risk factors for postoperative hypoxemia in ATAAD patients. While PaO2/FiO2 before extubating were independent risk factors for long-term mortality, indicating that active correction of hypoxemia and maintain a higher PaO2/FiO2 before extubating may help to improve the prognosis of the ATAAD patients.
Subject(s)
Aortic Dissection , Respiratory Distress Syndrome , Humans , Overweight/complications , Hypoxia/epidemiology , Hypoxia/etiology , Aortic Dissection/surgery , Prognosis , Retrospective Studies , Risk Factors , Respiratory Distress Syndrome/complicationsABSTRACT
NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT.
Subject(s)
Nanoparticles , Photothermal Therapy , Phototherapy , Cell Line, Tumor , Optical Imaging , Polymers/chemistry , Nanoparticles/chemistryABSTRACT
The luminescence of traditional phosphorescence-based hypoxia probes is limited to the visible and first near-infrared wavelength regions (<1000 nm), which has defects of higher light scattering and lower penetration depth in contrast with the second near-infrared wavelength window (NIR-II, 1000-1700 nm) for optical bioimaging. Herein, 5,15-bis(2,6-bis(dodecyloxy)phenyl)-porphyrin platinum(II) (PpyPt) with J-aggregation induced NIR-II phosphorescence is reported. J-aggregates of PpyPt are confirmed by the X-ray diffraction data in the crystalline state. Moreover, the emission and excitation spectra of PpyPt in the solid states reveal NIR-II luminescence feature of PpyPt in J-aggregates. More importantly, by preparation of water-soluble PpyPt nanoparticles (PpyPt NPs4.76 ) with J-aggregates, it has NIR-II phosphorescent lifetime of microseconds and good oxygen-sensitivity in water. Moreover, the good biological hypoxia-sensing potential of PpyPt NPs4.76 is demonstrated in cells and 4T1-tumor-bearing mice. This study provides an efficient strategy to design NIR-II phosphorescent probe for sensitive tumor-hypoxia detection through the construction of J-aggregates.
Subject(s)
Neoplasms , Porphyrins , Animals , Hypoxia/diagnostic imaging , Luminescent Measurements , Mice , Neoplasms/diagnostic imaging , Optical Imaging , Spectroscopy, Near-Infrared/methods , WaterABSTRACT
Background: The association between hypernatremia and delirium after cardiac surgery has rarely been investigated. This study aimed to determine whether hypernatremia increases the risk of delirium after exposure. Materials and Methods: From April 2016 to June 2021, 7,831 consecutive patients receiving cardiac surgery were screened for potential enrollment. The primary outcome was postoperative delirium (POD). For the respective case of delirium, 10 controls were matched according to the index date within the nested case-control design. Hypernatremia exposure was defined as serum sodium > 145 mmol/L within 7 days before the index date. A generalized estimation equation was performed to assess excess risks for POD associated with hypernatremia, adjusted for demographics and clinical variables. Results: About 7,277 patients were included in the final analyses. About 669 (9.2%) patients with POD were assigned to the case group, and 6,690 controls were identified from the whole population. About 66.5% of the cases and 36.3% of the controls had hypernatremia exposure. After being adjusted to certain well-recognized confounding factors, hypernatremia showed a significant correlation with increased risk of delirium after cardiac surgery (adjusted OR, 1.73; 95% CI, 1.41~2.12). An e-value analysis suggested the robustness to unmeasured confounding. Conclusions: Hypernatremia was associated with an increased risk of delirium after cardiac surgery. This finding could have implications for risk stratification, early detection, and management of delirium in patients receiving cardiac surgery.
ABSTRACT
Near-infrared II (NIR-II, 1000-1700 nm) fluorescent imaging (FI) has been reported to achieve optical images with higher resolution and deeper penetration. Among the organic NIR-II small molecules, donor-acceptor-donor (D-A-D) type fluorescent agents have shown superior photophysical and biocompatible properties for FI applications but have ongoing limitations, such as the difficulty in further modifying them with drug-carrying functional groups or prodrugs. In this work, three D-A-D type NIR-II fluorophores with electron acceptors of 4,8-bis(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-1H,3H-benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT), 6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TTQ) and 4,6-bis(5-bromo-2-thienyl)thieno[3,4-c][1,2,5]thiadiazole (TTDT) have been successfully prepared. Their optical and imaging properties and stability were investigated via theoretical and experimental studies. The results demonstrated that TTDT-SF exhibited good NIR-II imaging ability. Importantly, TTDT-SF showed outstanding stability in an alkaline and redox environment. Subsequently, a stable atom transfer radical polymerization (ATRP) initiator, based on TTDT and its derivative water-soluble fluorescent polymer TTDT-TF-POEGMA, synthesized through ATRP, was successfully fabricated. It was demonstrated that TTDT-TF-POEGMA exhibited excellent fluorescence ability, great water solubility, effective light stability and great potential in tumor FI and image-guided surgery. In a word, this work has developed a new stable initiator with NIR-II fluorescent properties, which provides a platform for the development of water-soluble and multifunctional NIR-II fluorescent polymers for a broad range of applications.
Subject(s)
Neoplasms , Polymers , Fluorescent Dyes , Humans , Optical Imaging , PolymerizationABSTRACT
Fluorescence imaging (FI) in the second near-infrared region (NIR-II, 1000-1700 nm) has attracted great attention for brain tumor imaging due to its deep penetration and high resolution. However, traditional NIR-II organic fluorescent nanoparticles (NPs) are usually hindered by uncontrolled large size (~30-100 nm), marked aggregation-caused quenching (ACQ) effect, and limited blood circulation (~1-3 h), which have great impact on efficient NIR-II FI of deep brain tumors. Herein, starlike polymer brush-based ultrasmall TQFP-10 NPs, with bright NIR-II fluorescence, prolonged blood circulation, and enhanced tumor accumulation, are facilely prepared for efficient orthotopic glioblastoma (GBM) imaging. Compared with traditional method prepared NPs (physically coated TQF@NPs and PEG modified TQF-PEG5K NPs), the ultrasmall (~8 nm) TQFP-10 NPs display a higher NIR-II fluorescence QY (1.9%), which is 2.1- and 3.8-fold higher than TQF@NPs (0.9%) and TQF-PEG5K NPs (0.5%), respectively. In addition, TQFP-10 NPs present a 10.6-fold higher blood circulation half-life (t1/2 = 8.5 h) than that of TQF-PEG5K NPs. Consequently, TQFP-10 NPs exhibit 4.2- and 33-fold higher maximal tumor to normal tissue ratio in subcutaneous and in situ NIR-II FI of GBM, respectively, than TQF@NPs and TQF-PEG5K NPs, attractively realizing GBM imaging. This work provides a general strategy for constructing ultrasmall NIR-II fluorescent NPs with simultaneously improved NIR-II fluorescence and blood circulation for efficient brain tumor imaging.
Subject(s)
Glioblastoma , Nanoparticles , Cell Line, Tumor , Fluorescent Dyes , Glioblastoma/diagnostic imaging , Humans , Optical Imaging , PolymersABSTRACT
Single-component nanoplatforms combined with the second near-infrared optical window (NIR-II, 1000-1700 nm) fluorescence imaging (FI) and NIR-II photothermal therapy (PTT) have received increasing attention owing to their capacity for precise diagnosis, noninvasive therapy, and real-time monitoring of the therapeutic effects. However, most of the PTT treatments are performed in the NIR-I window (700-900 nm). Moreover, the design and development of conjugated polymers (P1, P2, and P3) with both bright NIR-II fluorescence and superior NIR-II photothermal effect remained a huge challenge. Therefore, three double-acceptor conjugated polymers were designed and developed by adjusting the molar ratios of two acceptors, TTQ and DPP. Subsequently, their corresponding nanoparticles were fabricated, and finally, nanoparticles based on the conjugated polymer P1 (P1 NPs) with both high NIR-II fluorescence intensity and superior NIR-II photothermal efficiency were selected and applied for NIR-II FI and NIR-II PTT. Importantly, the experiments of in vivo NIR-II FI and NIR-II PTT demonstrated that P1 NPs exhibited not only high accumulation in the tumour sites and high sign-to-background ratio (SBR) of vascular imaging, but also superior NIR-II PTT efficiency for tumour treatment.