Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

Realizing high-efficiency third harmonic generation via accidental bound states in the continuum.

The bound states in the continuum (BICs) have attracted much attention in designing metasurface due to their high Q-factor and effectiveness in suppressing radiational loss. Here we report on the realization of the third harmonic generation (THG) at a near-ultraviolet wavelength (343 nm) via accidental BICs in a metasurface. The absolute conversion efficiency of the THG reaches 1.13 × 10-5 at a lower peak pump intensity of 0.7 GW/cm2. This approach allows the generation of an unprecedentedly high nonlinear conversion efficiency with simple structures.

Noninvasive identification of HER2-low-positive status by MRI-based deep learning radiomics predicts the disease-free survival of patients with breast cancer.

OBJECTIVE: This study aimed to establish a MRI-based deep learning radiomics (DLR) signature to predict the human epidermal growth factor receptor 2 (HER2)-low-positive status and further verified the difference in prognosis by the DLR model. METHODS: A total of 481 patients with breast cancer who underwent preoperative MRI were retrospectively recruited from two institutions. Traditional radiomics features and deep semantic segmentation feature-based radiomics (DSFR) features were extracted from segmented tumors to construct models separately. Then, the DLR model was constructed to assess the HER2 status by averaging the output probabilities of the two models. Finally, a Kaplan‒Meier survival analysis was conducted to explore the disease-free survival (DFS) in patients with HER2-low-positive status. The multivariate Cox proportional hazard model was constructed to further determine the factors associated with DFS. RESULTS: First, the DLR model distinguished between HER2-negative and HER2-overexpressing patients with AUCs of 0.868 and 0.763 in the training and validation cohorts, respectively. Furthermore, the DLR model distinguished between HER2-low-positive and HER2-zero patients with AUCs of 0.855 and 0.750, respectively. Cox regression analysis showed that the prediction score obtained using the DLR model (HR, 0.175; p = 0.024) and lesion size (HR, 1.043; p = 0.009) were significant, independent predictors of DFS. CONCLUSIONS: We successfully constructed a DLR model based on MRI to noninvasively evaluate the HER2 status and further revealed prospects for predicting the DFS of patients with HER2-low-positive status. CLINICAL RELEVANCE STATEMENT: The MRI-based DLR model could noninvasively identify HER2-low-positive status, which is considered a novel prognostic predictor and therapeutic target. KEY POINTS: • The DLR model effectively distinguished the HER2 status of breast cancer patients, especially the HER2-low-positive status. • The DLR model was better than the traditional radiomics model or DSFR model in distinguishing HER2 expression. • The prediction score obtained using the model and lesion size were significant independent predictors of DFS.

Scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair in rheumatic mitral disease.

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.

Antigen specific VNAR screening in whitespotted bamboo shark (Chiloscyllium plagiosum) with next generation sequencing.

IgNAR exhibits significant promise in the fields of cancer and anti-virus biotherapies. Notably, the variable regions of IgNAR (VNAR) possess comparable antigen binding affinity with much smaller molecular weight (∼12 kDa) compared to IgNAR. Antigen specific VNAR screening is a changeling work, which limits its application in medicine and therapy fields. Though phage display is a powerful tool for VNAR screening, it has a lot of drawbacks, such as small library coverage, low expression levels, unstable target protein, complicating and time-consuming procedures. Here we report VANR screening with next generation sequencing (NGS) could effectively overcome the limitations of phage display, and we successfully identified approximately 3000 BAFF-specific VNARs in Chiloscyllium plagiosum vaccinated with the BAFF antigen. The results of modelling and molecular dynamics simulation and ELISA assay demonstrated that one out of the top five abundant specific VNARs exhibited higher binding affinity to the BAFF antigen than those obtained through phage display screening. Our data indicates NGS would be an alternative way for VNAR screening with plenty of advantages.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment: Diagnostic Performance by General and Breast Radiologists.

BACKGROUND. Abbreviated protocols could allow wider adoption of MRI in patients undergoing breast cancer neoadjuvant chemotherapy (NAC). However, abbreviated MRI has been explored primarily in screening settings. OBJECTIVE. The purpose of this article was to compare diagnostic performance of abbreviated MRI and full-protocol MRI for evaluation of breast cancer NAC response, stratifying by radiologists' breast imaging expertise. METHODS. This retrospective study included 203 patients with breast cancer (mean age, 52.1 ± 11.2 [SD] years) from two hospitals who underwent MRI before NAC initiation and after NAC completion before surgical resection from March 2017 to April 2021. Abbreviated MRI was extracted from full-protocol MRI and included the axial T2-weighted sequence and precontrast and single early postcontrast T1-weighted sequences. Three general radiologists and three breast radiologists independently interpreted abbreviated and full-protocol MRI in separate sessions, identifying enhancing lesions to indicate residual tumor and measuring lesion size. The reference standard was presence and size of residual tumor on pathologic assessment of post-NAC surgical specimens. RESULTS. A total of 50 of 203 patients had pathologic complete response (pCR). Intraobserver and interobserver agreement for abbreviated and full-protocol MRI for general and breast radiologists ranged from substantial to nearly perfect (κ = 0.70-0.81). Abbreviated MRI compared with full-protocol MRI showed no significant difference for general radiologists in sensitivity (54.7% vs 57.3%, p > .99), specificity (92.8% vs 95.6%, p = .29), or accuracy (83.4% vs 86.2%, p = .30), nor for breast radiologists in sensitivity (60.0% vs 61.3%, p > .99), specificity (94.6% vs 97.4%, p = .22), or accuracy (86.0% vs 88.5%, p = .30). Sensitivity, specificity, and accuracy were not significantly different between protocols for any reader individually (p > .05). Mean difference in residual tumor size on MRI relative to pathology for abbreviated protocol ranged for general radiologists from -0.19 to 0.03 mm and for breast radiologists from -0.15 to -0.05 mm, and for full protocol ranged for general radiologists from 0.57 to 0.65 mm and for breast radiologists from 0.66 to 0.79 mm. CONCLUSION. Abbreviated compared with full-protocol MRI showed similar intraobserver and interobserver agreement and no significant difference in diagnostic performance. Full-protocol MRI but not abbreviated MRI slightly overestimated pathologic tumor sizes. CLINICAL IMPACT. Abbreviated protocols may facilitate use of MRI for post-NAC response assessment by general and breast radiologists.

Ileum tissue single-cell mRNA sequencing elucidates the cellular architecture of pathophysiological changes associated with weaning in piglets.

BACKGROUND: In mammals, transitioning from sole milk uptake to the intake of solid feed results in dramatic developmental changes in intestinal function and immunological status. In fact, weaning stress is often accompanied by intestinal inflammatory processes. To develop effective intervention strategies, it is necessary to characterize the developmental pattern and immune response that occurs on weaning, as we have done in this study for piglets. RESULTS: To comprehensively delineate cell heterogeneity in ileum tissues and the underlying mechanisms in weaning-induced intestinal inflammation of piglets, we have analyzed the transcriptomes of 42,149 cells from ileum mucosa of normally suckling and post-weaned piglets. There were 31 cell subtypes including epithelial, stromal, and immune cells. A bifurcating trajectory was inferred to separate secretory and absorptive lineages. Integrated cross-species datasets showed well-conserved cellular architectures and transcription signatures between human and pig. Comparative analyses of cellular components, cell-cell communications, and molecular states revealed that T cell subpopulations were significantly altered in weaned piglets. We found that T helper (Th) 17 functional plasticity across changes in the cytokine milieu and the enrichment of granzyme B (GZMB)-expressing cytotoxic T cells potentially exacerbate mucosal inflammation via mitochondrial dysfunction in epithelial cells. CONCLUSIONS: Our work has elucidated the single-cell molecular characteristics of the piglet ileum before and after weaning. We have provided an atlas that portrays the landscape of the intestinal pathophysiological inflammatory process associated with weaning, finding a level of conservation between human and pig that support the use of piglets as a model for human infants.

High total bilirubin-to-uric acid ratio predicts poor sleep quality after acute ischemic stroke: a prospective nested case-control study.

BACKGROUND: Sleep disorders are prevalent after stroke, resulting in high recurrence rates and mortality. But the biomarkers of sleep disorders in stroke patients remain to be elucidated. This study aimed to explore the relationship between total bilirubin-to-uric acid ratio (TUR) and sleep quality after acute ischemic stroke (AIS). METHODS: Three hundred twenty-six AIS patients were recruited and followed up 1 month after stroke in our study. Serum total bilirubin and uric acid levels were obtained within 24 h after admission. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality 1 month after stroke. We conducted receiver operating characteristic (ROC) curve analysis and screened the optimal biomarker to differentiate sleep disorders after stroke. Then the TUR was stratified according to the best cut-off value (0.036) of the ROC and further analysed by binary logistic regression analysis. Additionally, the interaction was used to explore the difference in its effect on post-stroke sleep quality in different subgroups. RESULTS: Three hundred thirty-one patients (40.2%) were considered as having poor sleep quality during the one-month follow-up. Compared to patients with good sleep, patients with poor sleep were more likely to have higher TUR (IQR), 0.05 (0.03-0.06) versus 0.03 (0.02-0.04), P < 0.001. After adjusting for confounding factors, binary regression analysis demonstrated that a high TUR (≥0.036) was independently related to post-stroke poor sleep quality (OR = 3.75, 95% CI = 2.02-6.96, P < 0.001). CONCLUSIONS: High TUR is associated with an increased risk of poor sleep quality in AIS patients, especially in females, diabetics, and patients with hyperlipidaemia.

Imaging features of gadoxetic acid-enhanced MR imaging for evaluation of tumor-infiltrating CD8 cells and PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: Tumor-infiltrating CD8 cells and expression of programmed cell death ligand 1 (PD-L1) are immune checkpoint markers in patients with hepatocellular carcinoma (HCC). We aimed to determine the ability of preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings to predict CD8 cell density and PD-L1 expression in HCC. METHODS: A total of 120 patients with HCC who underwent 3.0-T gadoxetic acid-enhanced MRI before curative resection from January 2016 to June 2020 were enrolled and divided into a training set (n = 84) and a testing set (n = 36). Thirty-four patients with advanced stage HCC who received anti-PD-1 inhibitor between January 2017 and April 2020 and underwent pretreated gadoxetic acid-enhanced MRI scans were enrolled in an independent validation set. PD-L1 expression and CD8 cell infiltration were assessed with immunohistochemical staining, respectively. Two radiologists blinded to pathology results evaluated the pretreated MR features in consensus. Logistic regression and the receiver operating characteristic curve (ROC) analyses were used to determine the value of image features to predict high CD8 cell density, PD-L1 positivity and the combination of high CD8 cell density and PD-L1 positivity in HCC in the training set and validated the findings in the testing set. The associations of MRI predictors with the objective response to immunotherapy were assessed in the independent validation. RESULTS: In the training set, the independent MRI predictors were irregular tumor margin (ITM, P = 0.008) and peritumoral low signal intensity (PLSI) on hepatobiliary phase (HBP) images (P < 0.001) for PD-L1 positivity, absence of an enhancing capsule (AEC, P = 0.001) and PLSI on HBP images (P = 0.025) for high CD8 cell density, and PLSI on HBP images (P = 0.001) and ITM (P = 0.023) for the both. The area under the curves (AUCs) of the predictive models for evaluating PD-L1 positivity, high CD8 cell density and the combination of high CD8 cell density and PD-L1 positivity were 0.810 and 0.809, 0.740 and 0.728, and 0.809 and 0.874 in the training and testing set, respectively. The objective response was demonstrated to be associated with the combination of PLSI on HBP images and ITM (PHI, P = 0.004), and the combination of PLSI on HBP images and AEC (PHA, P = 0.012) in the independent validation set. CONCLUSIONS: Pretreated MRI features have the potential to identify patients with HCC in an immune-activated state and predict outcomes of immunotherapy. Trial registration The study was retrospectively registered on March 5, 2020 with registration no. [2020] 02-012-01.

Realizing transmissive and reflective focusing with an on-chip metalens.

A metalens made of compact planar metastructure exhibits an excellent capability of focusing. The high-quality transmissive and reflective focusing simultaneously provides Fourier transform (FT) operation for optical information processing. Here we show a transflective on-chip metalens (TOM) made of orthogonal nano-grooves (ONGs). The TOM simultaneously converges transmitted and reflected (T&R) waves to the designed focal points. By adjusting the phase gradient profiles provided by the ONGs, the focal lengths of the T&R in-plane waves can be independently tuned. Our simulations show that the TOM possesses the advantages of broadband (>400 nm bandwidth) and high-focusing-efficiency (∼60%) dual-focusing capability. Further, we utilize the TOM to build a one-to-two 4-f optical system. Two different spatial filtering operations based on FT can be simultaneously implemented in axial transmission and off-axis reflection channels for one input signal. We expect that the dual-focusing metalens approach can realize parallel optical processing in on-chip optical computing, spatial filtering, and beyond.

Multichannel Distribution and Transformation of Entangled Photons with Dielectric Metasurfaces.

Photonic quantum information processing relies on operating the quantum state of photons, which usually involves bulky optical components unfavorable for system miniaturization and integration. Here, we report on the transformation and distribution of polarization-entangled photon pairs with multichannel dielectric metasurfaces. The entangled photon pairs interact with metasurface building blocks, where the geometrical-scaling-induced phase gradients are imposed, and are transformed into two-photon entangled states with the desired polarization. Two metasurfaces, each simultaneously distributing polarization-entangled photons to spatially separated multiple channels M (N), may accomplish M×N channels of entanglement distribution and transformation. Experimentally we demonstrate 2×2 and 4×4 distributed entanglement states, including Bell states and superposition of Bell states, with high fidelity and strong polarization correlation. We expect this approach paves the way for future integration of quantum information networks.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Performance of radiomics models for tumour-infiltrating lymphocyte (TIL) prediction in breast cancer: the role of the dynamic contrast-enhanced (DCE) MRI phase.

OBJECTIVE: To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. MATERIALS AND METHODS: This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. RESULTS: Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. CONCLUSION: The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. KEY POINTS: • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Comparison of Gadobenate-Enhanced MRI and Gadoxetate-Enhanced MRI for Hepatocellular Carcinoma Detection Using LI-RADS Version 2018: A Prospective Intraindividual Randomized Study.

BACKGROUND. Gadobenate and gadoxetate show different degrees of intracellular accumulation within hepatocytes, potentially impacting these agents' relative performance for hepatocellular carcinoma (HCC) diagnosis. OBJECTIVE. The purpose of this article was to perform an intraindividual comparison of gadobenate-enhanced MRI and gadoxetate-enhanced MRI for detection of HCC and to assess the impact of inclusion of hepatobiliary phase images on HCC detection for both agents. METHODS. This prospective study enrolled 126 patients (112 men, 14 women; mean age, 52.3 years) at high risk for HCC who consented to undergo two 3-T liver MRI examinations (one using gadobenate [0.05 mmol/kg], one using gadoxetate [0.025 mmol/kg]) separated by 7-14 days. The order of the two contrast agents was randomized. All examinations included postcontrast dynamic and hepatobiliary phase images (120 minutes for gadobenate, 20 minutes for gadoxetate). Three radiologists independently reviewed the gadobenate and gadoxetate examinations in separate sessions and recorded the location of detected observations. Observations were classified using LI-RADS version 2018 and using a LI-RADS modification whereby hepatobiliary phase hypointensity may upgrade observations from category LR-4 to LR-5. Observations classified as LR-5 were considered positive interpretations for HCC. Diagnostic performance for histologically confirmed HCC (n = 96) was assessed. RESULTS. Across readers, sensitivity for HCC for gadobenate versus gadoxetate was 74.0-80.2% versus 54.2-67.7% using dynamic images alone and 82.1-87.4% versus 66.3-81.1% using dynamic and hepatobiliary phase images. For HCCs measuring 1.0-2.0 cm, sensitivity for gadobenate versus gadoxetate was 61.9% (all readers) versus 38.1-57.1% using dynamic images alone and 76.2-85.7% versus 52.4-61.9% using dynamic and hepatobiliary phase images. PPV for HCC ranged from 88.6% to 97.4% across readers, agents, and image sets. CONCLUSION. Sensitivity for HCC was higher for gadobenate than for gadoxetate, whether using dynamic images alone or dynamic and hepatobiliary phase images; the improved sensitivity using gadobenate was more pronounced for small HCCs. Whereas hepatobiliary phase images improved sensitivity for both agents, sensitivity of gadobenate using dynamic images alone compared favorably with that of gadoxetate using dynamic and hepatobiliary phase images. CLINICAL IMPACT. The findings support gadobenate as a preferred agent over gadoxetate when performing liver MRI in patients at high risk for HCC.

GSK-3ß inhibition protects human nucleus pulposus cell against oxidative stress-inducing apoptosis through mitochondrial pathway.

BACKGROUND: Oxidative stress in the intervertebral disc leads to nucleus pulposus (NP) degeneration by inducing cell apoptosis. However, the molecular mechanisms underlying this process remain unclear. Increasing evidence indicates that GSK-3ß is related to cell apoptosis induced by oxidative stress. In this study, we explored whether GSK-3ß inhibition protects human NP cell against apoptosis under oxidative stress. METHODS AND RESULTS: Immunofluorescence staining was used to show the expression of GSK-3ß in human NP cells (NPCs). Flow cytometry, mitochondrial staining and western blot (WB) were used to detect apoptosis of treated NPCs, changes of mitochondrial membrane potential and the expression of mitochondrial apoptosis-related proteins using GSK-3ß specific inhibitor SB216763. Co-Immunoprecipitation (Co-IP) was used to demonstrate the interaction between GSK-3ß and Bcl-2. We delineated the protective effect of GSK-3ß specific inhibitor SB216763 on human NPCs apoptosis induced by oxidative stress in vitro. Further, we showed SB216763 exert the protective effect by preservation of the mitochondrial membrane potential and inhibition of caspase 3/7 activity during oxidative injury. The detailed mechanism underlying the antiapoptotic effect of GSK-3ß inhibition was also studied by analyzing mitochondrial apoptosis pathway in vitro. CONCLUSIONS: We concluded that the GSK-3ß inhibitor SB216763 protected mitochondrial membrane potential to delay nucleus pulposus cell apoptosis by inhibiting the interaction between GSK-3ß and Bcl-2 and subsequently reducing cytochrome c(Cyto-C) release and caspase-3 activation. Together, inhibition of GSK-3ß using SB216763 in NPCs may be a favorable therapeutic strategy to slow intervertebral disc degeneration.

Effects of dietary protein on gut development, microbial compositions and mucin expressions in mice.

AIMS: Dietary protein, as an important macronutrient, widely participates in host growth and metabolism. In this study, effects of different protein levels (14, 20 and 26%) on the gut development, microbial compositions and mucin expressions were studied in C57BL/6 mice. METHODS AND RESULTS: The results showed that body weight and the relative weight of stomach and gut were decreased in low-protein diet-fed mice, whereas high-protein diet significantly reduced the villus length and area of jejunum. Goblet cells number in the jejunum was reduced in the low-protein group, which was reversed by dietary a high-protein diet. In addition, high-protein diet notably reduced microbial diversity and changed the microbial compositions at the phylum level, such as Bacteroides, Proteobacteria, Actinomycetes and Deferribacteres. Furthermore, high-protein diet significantly increased mucin2, mucin3 and mucin4 expressions in the jejunum, but downregulated mucin1, mucin2, mucin4 and TFF3 in the ileum, indicating a tissue-dependent manner. CONCLUSIONS: Together, high-protein diet may impair gut development, microbial balance and mucin system, and a low-protein diet is suggested to promote a healthy lifestyle. SIGNIFICANCE AND IMPACT OF STUDY: Mucin influenced gut development (villus index and goblet cell number) through remodelling gut microbes, as low and high protein levels resulted in contrary expression levels of mucin in jejunum and ileum.

Influence of continuing nursing care team mode on the rehabilitation of patients with pancreatic cancer after postoperative daily chemotherapy.

OBJECTIVE: This study aimed to investigate the effect of continuing nursing care team mode on postoperative outpatient chemotherapy patients with pancreatic cancer. METHODS: One-hundred patients receiving postoperative outpatient chemotherapy for pancreatic cancer between September 2019 and December 2020 were enrolled in this study and divided into two groups, an intervention group and a control group (n = 50 each), by random number table method or coin tossing method. The patients in the intervention group were followed up using continuing nursing care team mode, while those in the control group were followed up using the traditional telephone follow-up mode. The effects of the two modes on patients' self-care ability, quality of life, anxiety, hospital waiting time, and the nurses' communication ability and self-efficacy were compared and analyzed. RESULTS: The self-care ability and quality of life of the patients in the intervention group were better than those of the control group (p < 0.05), the anxiety score and hospital waiting times were lower than those in the control group (p < 0.05), and the communication ability and general self-efficacy of the nurses were also significantly stronger than those in the control group (p < 0.05). CONCLUSION: The application of the continuing nursing care team mode for follow-up can improve the self-care ability and quality of life of patients, effectively reduce the anxiety and hospital waiting time of outpatient chemotherapy patients, and improve the nurses' communication ability and general self-efficacy. Therefore, this practice is worthy of clinical popularization.

Effects of melatonin on intestinal function and bacterial compositions in sucking piglets.

Melatonin has been reported to affect intestinal function by targeting microbiome, morphological structure, barrier integrity and nutrient absorptive system. While the effect of melatonin on intestinal development in newborn infants is obscure, thus, this study firstly attempted to investigate the hypothesis that melatonin treatment improves intestinal development in sucking piglets. 14 healthy newborn piglets received 10 ml melatonin solution (1 mg/ml) or drinking water (n = 7) for 21 days. The results showed that oral administration of melatonin increased liver relative weight (p < 0.05) but failed to affect growth performance in sucking piglets (p > 0.05). Immunostaining jejunal samples from melatonin group showed high expressions of nnos and claudin1, indicating that melatonin improved intestinal neural development and barrier integrity. Also, melatonin promoted intestinal absorptive function evidenced by the increased serum proline concentration in melatonin-treated piglets compared with the control (p < 0.05). Gut microbiota compositions were tested by 16S rDNA sequencing and the results showed that melatonin increased the relative abundance of Actinobacteria compared with the control (p < 0.05) at the phylum level. However, Selenomonadales was markedly reduced compared with the control at the order level (p < 0.05). Gut and faecal volatile fatty acids were tested to evaluate the microbiota metabolism, but no difference was noticed in volatile fatty acid concentrations (p > 0.05). Melatonin improved intestinal development by affecting neural development, barrier integrity, nutrient absorption and microbiota in sucking piglets.

Dynamic Parameter Calibration Framework for Opinion Dynamics Models.

In the past decade, various opinion dynamics models have been built to depict the evolutionary mechanism of opinions and use them to predict trends in public opinion. However, model-based predictions alone cannot eliminate the deviation caused by unforeseeable external factors, nor can they reduce the impact of the accumulated random error over time. To solve this problem, we propose a dynamic framework that combines a genetic algorithm and a particle filter algorithm to dynamically calibrate the parameters of the opinion dynamics model. First, we design a fitness function in accordance with public opinion and search for a set of model parameters that best match the initial observation. Second, with successive observations, we tracked the state of the opinion dynamic system by the average distribution of particles. We tested the framework by using several typical opinion dynamics models. The results demonstrate that the proposed method can dynamically calibrate the parameters of the opinion dynamics model to predict public opinion more accurately.

Cardiac parameters affect prognosis in patients with non-large atherosclerotic infarction.

BACKGROUND: Although large artery atherosclerosis (LAA) is the most common type of cerebral infarction, non-LAA is not uncommon. The purpose of this paper is to investigate the prognosis of patients with non-LAA and to establish a corresponding nomogram. PATIENTS AND METHODS: Between June 2016 and June 2017, we had 1101 admissions for acute ischemic stroke (AIS). Of these, 848 were LAA and 253 were non-LAA. Patients were followed up every 3 months with a minimum of 1 year of follow-up. After excluding patients who were lost follow-up and patients who did not meet the inclusion criteria, a total of 152 non-LAA patients were included in this cohort study. After single-factor analysis and multifactor logistic regression analysis, the risk factors associated with prognosis were derived and different nomograms were developed based on these risk factors. After comparison, the best model is derived. RESULTS: Logistics regression found that the patient's National Institutes of Health Stroke Scale (NIHSS) score, ejection fraction (EF), creatine kinase-MB (CK-MB), age, neutrophil-to-lymphocyte ratio (NLR), aspartate aminotransferase (AST), and serum albumin were independently related to the patient's prognosis. We thus developed three models: model 1: single NIHSS score, AUC = 0.8534; model 2, NIHSS + cardiac parameters (CK-MB, EF), AUC = 0.9325; model 3, NIHSS + CK-MB + EF + age + AST + NLR + albumin, AUC = 0.9598. We compare the three models: model 1 vs model 2, z = - 2.85, p = 0.004; model 2 vs model 3, z = - 1.58, p = 0.122. Therefore, model 2 is considered to be the accurate and convenient model. CONCLUSIONS: Predicting the prognosis of patients with non-LAA is important, and our nomogram, built on the NIHSS and cardiac parameters, can predict the prognosis accurately and provide a powerful reference for clinical decision making.