Tert-Butylhydroquinone alleviates insulin resistance and liver steatosis in diabetes.

OBJECTIVES: This work aimed to determine tert-Butylhydroquinone (TBHQ)'s effects on insulin resistance (IR) and liver steatosis in diabetic animals and to explore the underpinning mechanisms. MATERIALS AND METHODS: Male ApoE-/-mice underwent streptozocin (STZ) administration while receiving a sucrose/fat-rich diet for type 2 diabetes mellitus (T2DM) establishment. This was followed by a 6-week TBHQ administration. Body weight, fasting (FBG) and postprandial (PBG) blood glucose amounts, and insulin concentrations were measured, and the oral glucose tolerance test (OGTT) was carried out. Hematoxylin and eosin (H and E) staining and immunoblot were carried out for assessing histology and protein amounts in the liver tissue samples. In addition, cultured HepG2 cells were administered HClO and insulin for IR induction, and immunoblot was carried out for protein evaluation. Finally, the cells were stained with the Hoechst dye for apoptosis evaluation. RESULTS: The model animals showed T2DM signs, and TBHQ decreased FBG, ameliorated glucose tolerance and reduced liver steatosis in these animals. In addition, TBHQ markedly upregulated AMPKα2, GLUT4 and GSK3 ß, as well as phosphorylated PI3K and AKT in the liver of mice with T2DM. In agreement, TBHQ decreased HClO-and insulin-related IR in cells and suppressed apoptosis through AMPKα2/PI3K/AKT signaling. CONCLUSIONS: TBHQ alleviates IR and liver steatosis in a mouse model of T2DM likely through AMPKα2/PI3K/AKT signaling.

Combined model of radiomics, clinical, and imaging features for differentiating focal pneumonia-like lung cancer from pulmonary inflammatory lesions: an exploratory study.

BACKGROUND: Only few studies have focused on differentiating focal pneumonia-like lung cancer (F-PLC) from focal pulmonary inflammatory lesion (F-PIL). This exploratory study aimed to evaluate the clinical value of a combined model incorporating computed tomography (CT)-based radiomics signatures, clinical factors, and CT morphological features for distinguishing F-PLC and F-PIL. METHODS: In total, 396 patients pathologically diagnosed with F-PLC and F-PIL from two medical institutions between January 2015 and May 2021 were retrospectively analyzed. Patients from center 1 were included in the training (n = 242) and internal validation (n = 104) cohorts. Moreover, patients from center 2 were classified under the external validation cohort (n = 50). The clinical and CT morphological characteristics of both groups were compared first. And then, a clinical model incorporating clinical and CT morphological features, a radiomics model reflecting the radiomics signature of lung lesions, and a combined model were developed and validated, respectively. RESULTS: Age, gender, smoking history, respiratory symptoms, air bronchogram, necrosis, and pleural attachment differed significantly between the F-PLC and F-PIL groups (all P < 0.05). For the clinical model, age, necrosis, and pleural attachment were the most effective factors to differentiate F-PIL from F-PLC, with the area under the curves (AUCs) of 0.838, 0.819, and 0.717 in the training and internal and external validation cohorts, respectively. For the radiomics model, five radiomics features were found to be significantly related to the identification of F-PLC and F-PIL (all P < 0.001), with the AUCs of 0.804, 0.877, and 0.734 in the training and internal and external validation cohorts, respectively. For the combined model, five radiomics features, age, necrosis, and pleural attachment were independent predictors for distinguishing between F-PLC and F-PIL, with the AUCs of 0.915, 0.899, and 0.805 in the training and internal and external validation cohorts, respectively. The combined model exhibited a better performance than had the clinical and radiomics models. CONCLUSIONS: The combined model, which incorporates CT-based radiomics signatures, clinical factors, and CT morphological characteristics, is effective in differentiating F-PLC from F-PIL.

Multi-level encryption of information in morphing hydrogels with patterned fluorescence.

Fluorescent hydrogels have attracted tremendous attention recently in the field of information security due to the booming development of information technology. Along this line, it is highly desired to improve the security level of concealed information by the advancements of materials and encryption technologies. Here we report multi-level encryption of information in a bilayer hydrogel with shape-morphing ability and patterned fluorescence. This hydrogel is composed of a fluorescence layer containing chromophore units in the poly(acrylic acid) network and an active layer with UV-absorption agents in the poly(N-isopropylacrylamide-co-acrylic acid) network. The former layer exhibits tunable fluorescence tailored by UV light irradiation to induce unimer-to-dimer transformation of the chromophores, facilitating the write-in of information through photolithography. The latter layer is responsive to temperature, enabling morphing of the bilayer hydrogel. Therefore, the bilayer hydrogel encoded with patterned fluorescent patterns can deform into three-dimensional configurations at room temperature to conceal the information, which is readable only after successive procedures of shape recovery at an appropriate temperature and under UV light irradiation from the right direction. The combination of morphing materials and patterned fluorescence as a new avenue to improve the encryption level of information should merit the design of other smart materials with integrated functions for specific applications.

Paper without a Trail: Time-Dependent Encryption using Pillar[5]arene-Based Host-Guest Invisible Ink.

A stimuli-responsive invisible ink for time-dependent encryption of information is reported. Consisting of a pillar[5]arene-based supramolecular network grafted with spiropyran moieties, these materials display time-dependent photochromic behavior with tailorable fading rates. Ultraviolet (UV) light results in isomerization of the colorless spiropyran to the corresponding colored merocyanine, while visible light or heat causes the reverse isomerization with a rate that is dependent on the density of host-guest crosslinks. The kinetics of discoloration are a function of merocyanine aggregation, which becomes more pronounced as the host-guest crosslink density is increased, leading to a reduced conversion rate and slower time-dependent fading. The degree of crosslinking, and hence the fading rate, may be modulated via the addition of unbound pillar[5]arene host or nitrile guest as competitors. Time-dependent information encryption is enabled by combining selective placement of host and guest competitors and UV patterning. UV patterning provides an initially "false" image that does not reveal the desired information, and it is only after a given time that the encrypted data appears. This work provides a unique approach to enhance the security of information storage associated with offline portable data encryption.

Development and validation of a novel risk assessment model to estimate the probability of pulmonary embolism in postoperative patients.

Pulmonary embolism (PE) is a leading cause of mortality in postoperative patients. Numerous PE prevention clinical practice guidelines are available but not consistently implemented. This study aimed to develop and validate a novel risk assessment model to assess the risk of PE in postoperative patients. Patients who underwent Grade IV surgery between September 2012 and January 2020 (n = 26,536) at the Affiliated Dongyang Hospital of Wenzhou Medical University were enrolled in our study. PE was confirmed by an identified filling defect in the pulmonary artery system in CT pulmonary angiography. The PE incidence was evaluated before discharge. All preoperative data containing clinical and laboratory variables were extracted for each participant. A novel risk assessment model (RAM) for PE was developed with multivariate regression analysis. The discrimination ability of the RAM was evaluated by the area under the receiver operating characteristic curve, and model calibration was assessed by the Hosmer-Lemeshow statistic. We included 53 clinical and laboratory variables in this study. Among them, 296 postoperative patients developed PE before discharge, and the incidence rate was 1.04%. The distribution of variables between the training group and the validation group was balanced. After using multivariate stepwise regression, only variable age (OR 1.070 [1.054-1.087], P < 0.001), drinking (OR 0.477 [0.304-0.749], P = 0.001), malignant tumor (OR 2.552 [1.745-3.731], P < 0.001), anticoagulant (OR 3.719 [2.281-6.062], P < 0.001), lymphocyte percentage (OR 2.773 [2.342-3.285], P < 0.001), neutrophil percentage (OR 10.703 [8.337-13.739], P < 0.001), red blood cell (OR 1.872 [1.384-2.532], P < 0.001), total bilirubin (OR 1.038 [1.012-1.064], P < 0.001), direct bilirubin (OR 0.850 [0.779-0.928], P < 0.001), prothrombin time (OR 0.768 [0.636-0.926], P < 0.001) and fibrinogen (OR 0.772 [0.651-0.915], P < 0.001) were selected and significantly associated with PE. The final model included four variables: neutrophil percentage, age, malignant tumor and lymphocyte percentage. The AUC of the model was 0.949 (95% CI 0.932-0.966). The risk prediction model still showed good calibration, with reasonable agreement between the observed and predicted PE outcomes in the validation set (AUC 0.958). The information on sensitivity, specificity and predictive values according to cutoff points of the score in the training set suggested a threshold of 0.012 as the optimal cutoff value to define high-risk individuals. We developed a new approach to select hazard factors for PE in postoperative patients. This tool provided a consistent, accurate, and effective method for risk assessment. This finding may help decision-makers weigh the risk of PE and appropriately select PE prevention strategies.

Dual-Encryption in a Shape-Memory Hydrogel with Tunable Fluorescence and Reconfigurable Architecture.

Materials capable of shape-morphing and/or fluorescence imaging have practical significances in the fields of anti-counterfeiting, information display, and information protection. However, it's challenging to realize these functions in hydrogels due to the poor mechanical properties and lack of tunable fluorescence. A tough hydrogel with good shape-memory ability and phototunable fluorescence is reported here, which affords reprogrammable shape designing and information encoding for dual-encryption. This hydrogel is prepared by incorporating donor-acceptor chromophore units into a poly(1-vinylimidazole-co-methacrylic acid) network, in which the dense intra- and interchain hydrogen bonds lead to desirable features including high stiffness, high toughness, and temperature-mediated shape-memory property. Additionally, the hydrogel shows photomediated tunable fluorescence through a unimer-to-dimer transformation of the chromophores. By combining photolithography and origami/kirigami designs, hydrogel sheets encoded with fluorescent patterns can deform into specific 3D configurations. The geometrically encrypted fluorescent information in the architected hydrogels is readable only after sequential shape recovery and UV light irradiation. As demonstrated by proof-of-concept experiments, both the fluorescent pattern and the 3D configuration are reprogrammable, facilitating repeated information protection and display. The design of tough hydrogels with rewritable fluorescent patterns and reconfigurable shapes should guide the future development of smart materials with improved security and wider applications in aqueous environments.

Development and Validation of a Combined Model for Preoperative Prediction of Lymph Node Metastasis in Peripheral Lung Adenocarcinoma.

BACKGROUND: Based on the "seed and soil" theory proposed by previous studies, we aimed to develop and validate a combined model of machine learning for predicting lymph node metastasis (LNM) in patients with peripheral lung adenocarcinoma (PLADC). METHODS: Radiomics models were developed in a primary cohort of 390 patients (training cohort) with pathologically confirmed PLADC from January 2016 to August 2018. The patients were divided into the LNM (-) and LNM (+) groups. Thereafter, the patients were subdivided according to TNM stages N0, N1, N2, and N3. Radiomic features from unenhanced computed tomography (CT) were extracted. Radiomic signatures of the primary tumor (R1) and adjacent pleura (R2) were built as predictors of LNM. CT morphological features and clinical characteristics were compared between both groups. A combined model incorporating R1, R2, and CT morphological features, and clinical risk factors was developed by multivariate analysis. The combined model's performance was assessed by receiver operating characteristic (ROC) curve. An internal validation cohort containing 166 consecutive patients from September 2018 to November 2019 was also assessed. RESULTS: Thirty-one radiomic features of R1 and R2 were significant predictors of LNM (all P < 0.05). Sex, smoking history, tumor size, density, air bronchogram, spiculation, lobulation, necrosis, pleural effusion, and pleural involvement also differed significantly between the groups (all P < 0.05). R1, R2, tumor size, and spiculation in the combined model were independent risk factors for predicting LNM in patients with PLADC, with area under the ROC curves (AUCs) of 0.897 and 0.883 in the training and validation cohorts, respectively. The combined model identified N0, N1, N2, and N3, with AUCs ranging from 0.691-0.927 in the training cohort and 0.700-0.951 in the validation cohort, respectively, thereby indicating good performance. CONCLUSION: CT phenotypes of the primary tumor and adjacent pleura were significantly associated with LNM. A combined model incorporating radiomic signatures, CT morphological features, and clinical risk factors can assess LNM of patients with PLADC accurately and non-invasively.

Reconstructable Gradient Structures and Reprogrammable 3D Deformations of Hydrogels with Coumarin Units as the Photolabile Crosslinks.

Morphing hydrogels have versatile applications in soft robotics, flexible electronics, and biomedical devices. Controlling component distribution and internal stress within a hydrogel is crucial for shape-changing. However, existing gradient structures of hydrogels are usually non-reconstructable, once encoded by chemical reactions and covalent bonds. Fabricating hydrogels with distinct gradient structures is inevitable for every new configuration, resulting in poor reusability, adaptability, and sustainability that are disadvantageous for diverse applications. Herein, a hydrogel containing reversible photo-crosslinks that enable reprogramming of the gradient structures and 3D deformations into various configurations is reported. The hydrogel is prepared by micellar polymerization of hydrophobic coumarin monomer and hydrophilic acrylic acid. The presence of hexadecyltrimethylammonium chloride micelles increases the local concentration of coumarin units and also improves the mechanical properties of the hydrogel by forming robust polyelectrolyte/surfactant complexes that serve as the physical crosslinks. High-efficiency photodimerization and photocleavage reactions of coumarins are realized under 365 and 254 nm light irradiation, respectively, affording reversible tuning of the network structure of the hydrogel. Through photolithography, different gradient structures are sequentially patterned in one hydrogel that direct the deformations into distinct configurations. Such a strategy should be applicable for other photolabile hydrogels toward reprogrammable control of network structures and versatile functions.

Tertiary butylhydroquinone alleviated liver steatosis and increased cell survival via ß-arrestin-2/PI3K/AKT pathway.

OBJECTIVES: This study aimed to evaluate the effects and the underlying mechanisms of tertiary butylhydroquinone (TBHQ) on diabetic liver steatosis and cell survival. MATERIALS AND METHODS: We performed streptozocin injection and used a high-sugar-high-fat diet for mice to develop an animal model of type 2 diabetes mellitus (T2DM). Bodyweight, blood glucose levels, and content of insulin were measured on all of the mice. The liver tissues were observed by hematoxylin-eosin staining. Protein levels of the liver were measured by Western blot analysis in mice. Primary hepatocytes were induced by hypochlorous acid (HClO) and insulin to form insulin resistance (IR). Primary hepatocyte apoptosis was observed by Hoechst staining. The PI3K/AKT signaling pathway and ß-arrestin-2 factor were evaluated by Western blot assay. RESULTS: TBHQ reduced the blood glucose level and content of insulin in serum, increased body weight, and effectively alleviated liver steatosis in diabetic mice. TBHQ significantly up-regulated the expression of p-PI3K, p-AKT, GLUT4, GSK3ß, and ß-arrestin-2 in the liver of diabetic mice. Cell experiments confirmed that TBHQ increased the survival ability of primary hepatocytes, and TBHQ improved the expression of p-PI3K, p-AKT, GLUT4, and GSK3ß by activating ß-arrestin-2 in primary hepatocytes. CONCLUSION: TBHQ could alleviate liver steatosis and increase cell survival, and the mechanism is due in part to ß-arrestin-2 activation.

Hematological Indexes Can Be Used to Predict the Incidence of Hypothyroidism in Nasopharyngeal Carcinoma Patients after Radiotherapy.

BACKGROUND: This study explored the relationship between thyroid-associated antibodies, immune cells, and hypothyroidism to establish a predictive model for the incidence of hypothyroidism in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: A total of 170 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences between January 2015 and August 2018 were included. The complete blood count, biochemical, coagulation function, immune cells, and thyroid-associated antibodies tested before radiotherapy were evaluated. A logistic regression model was performed to elucidate which hematological indexes were related to hypothyroidism development. A predictive model for the incidence of hypothyroidism was established. Internal verification of the multifactor model was performed using the tenfold cross-validation method. RESULTS: The univariate analysis showed that immune cells had no statistically significant differences among the patients with and without hypothyroidism. Sex, N-stage, antithyroid peroxidase antibody (TPO-Ab), antithyroglobulin antibody (TG-Ab), thyroglobulin (TG), and fibrinogen (Fb) were associated with hypothyroidism. Males and early N-stage were protective factors of thyroid function, whereas increases in TPO-Ab, TG-Ab, TG, and Fb counts were associated with an increased rate of hypothyroidism incidence. The multivariate analysis showed that TPO-Ab, TG-Ab, TG, and Fb were independent predictors of hypothyroidism. The comprehensive effect of the significant model, including TPO-Ab, TG-Ab, TG, and Fb counts, represented the optimal method of predicting the incidence of radiation-induced hypothyroidism (AUC = 0.796). Tenfold cross-validation methods were applied for internal validation. The AUCs of the training and testing sets were 0.792 and 0.798, respectively. CONCLUSION: A model combining TPO-Ab, TG-Ab, TG, and Fb can be used to screen populations at a high risk of developing hypothyroidism after radiotherapy.

Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 µmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

Reversible Ion-Conducting Switch in a Novel Single-Ion Supramolecular Hydrogel Enabled by Photoresponsive Host-Guest Molecular Recognition.

A novel ion-conducting supramolecular hydrogel with reversible photoconductive properties in which the azobenzene motif, α-cyclodextrin (α-CD), and ionic liquid are grafted onto the gel matrix is reported. Host-guest interactions with different association constants between α-CD and azobenzene or the anionic part of the ionic liquid can be readily tuned by photoinduced trans-cis isomerization of the azobenzene unit. When irradiated by 365 nm light, α-CD prefers to form a complex with the anionic part of the ionic liquid, resulting in decreased ionic mobility and thus high resistance of the hydrogel. However, under 420 nm light irradiation, a more stable complex is again formed between α-CD and trans-azobenzene, thereby releasing the bound anions to regenerate the low-resistive hydrogel. As such, remote control of the ionic conductivity of the hydrogel is realized by simple host-guest chemistry. With the incorporation of a logic gate, this hydrogel is able to reversibly switch an electric circuit on and off by light irradiation with certain wavelengths. The concept of photoswitchable ionic conductivity of a hydrogel mediated by competitive molecular recognition is potentially promising toward the fabrication of optoelectronic devices and applications in bioelectronic technology.

Single Chromophore-Based White-Light-Emitting Hydrogel with Tunable Fluorescence and Patternability.

Bioluminescence is widespread in nature such as the jellyfish, which inspires scientists to design polymer hydrogels with tunable fluorescence. However, it remains a big challenge to develop white-light-emitting hydrogels with local tunability of the fluorescent behavior. Herein, we report a white fluorescent hydrogel prepared by one-pot micellar copolymerization of hydrophilic acrylamide and hydrophobic single donor-acceptor chromophore monomer, in which the unimer and the dimer of the chromophore coexist and generate high- and low-energy emission, respectively, under excitation. The fluorescent behavior of the hydrogel can be well tuned by phototreatment or heat treatment that induces unimer-to-dimer transformation of the chromophore and thus variation of the fluorescent color from blue to white and then to yellow. The fluorescence can also be reversibly switched off by forming terpyridine-Cu2+ chelate complexes and recovered by using chelating agent to extract the Cu2+ ions out of the gel matrix. These properties afford patterning the fluorescent hydrogel, which is transparent under daylight yet shows the pattern under ultraviolet light. These patterned fluorescent hydrogels should find applications in protected message display for improved information security.

Cooperative deformations of periodically patterned hydrogels.

Nature has shown elegant paradigms of smart deformation, which inspired biomimetic systems with controllable bending, folding, and twisting that are significant for the development of soft electronics and actuators. Complex deformations are usually realized by additively incorporating typical structures in selective domains with little interaction. We demonstrate the cooperative deformations of periodically patterned hydrogel sheets, in which neighboring domains mutually interact and cooperatively deform. Nonswelling disc gels are periodically positioned in a high-swelling gel. During the swelling process, the compartmentalized high-swelling gel alternately bends upward or downward to relieve the in-plane compression, but the overall integrated structure remains flat. The synergy between the elastic mismatch and the geometric periodicity selects the outcome pattern. Both experiment and modeling show that various types of cooperative deformation can be achieved by tuning the pattern geometry and gel properties. Different responsive polymers can also be patterned in one composite gel. Under stimulation, reversible transformations between different cooperative deformations are realized. The principle of cooperative deformation should be applicable to other materials, and the patterns can be miniaturized to the micrometer- or nanometer-scale level, providing the morphing materials with advanced functionalities for applications in various fields.

Programmed planar-to-helical shape transformations of composite hydrogels with bioinspired layered fibrous structures.

Self-shaping materials have attracted tremendous interest due to their promising applications in soft robotics, and flexible electronics, etc. In this field, a crucial issue is how to construct complex yet elaborate structures in active materials. Here, we present the fabrication of composite hydrogels with both in-plane and out-of-plane structural gradients by multi-step photolithography and the resulting controllable deformations. A patterned gel with a layered fibrous structure like bean pod is developed, which shows programmed deformations from a flat shape to a twisted helix. The parameters of the helix can be deliberately tuned. This approach enables patterning different responsive polymers in specific regions of composite gels, leading to multiple shape transformations under stimulations. The controllability of intricate structures, together with tunable responses of localized gels, facilitates the generation of complex internal stresses and three-dimensional deformations of composite gels toward specific applications.