Background Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC). Methods We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated fi liated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified fi ed as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models. Findings The CID exhibited significant fi cant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific fi c survival (DSS) among patients with RCC tumors measuring 3 cm or larger (all p < 0.001). Multivariate analyses confirmed fi rmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification fi cation among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84-0.92) - 0.92) in the training set, 0.92 (95%CI: 0.88-0.98) - 0.98) in the internal validation set, and 0.86 (95%CI: 0.81-0.90) - 0.90) in the external test set, surpassing existing prognostic models. Interpretation Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3 cm or larger.

BackgroundInsulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride–glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients.MethodsA total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride–glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes.ResultsThe TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan–Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors.ConclusionThe TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets.

BACKGROUND:Glucoregulatory protein 94 (Grp94) is necessary for the post-viral life cycle and plays a quality control role in viral proteins, but the role of Grp94 in regulating viral replication in host cells is not well known. Therefore, finding a compound that can regulate Grp94 will help us to study the mechanism of viral replication. Previously, we synthesized a coumarin pyrazoline derivative HCP1 that is an effective inhibitor of Grp94. We suppose that HCP1 may inhibit viral replication. OBJECTIVE:This study aimed to investigate the effect of HCP1 on the replication ability of Senecavirus A (SVA), so as to provide a target and a leading compound for revealing the pathogenic mechanism of the virus and developing antiviral drugs. METHODS:Rat cell lines BHK-21 and porcine cell lines PK-15 were infected with SVA, and the infected cells were treated with different concentrations of HCP1. The cell viability (CCK-8), virus titer (TCID50), autophagy level, and Grp94 expression were measured. RESULTS:The results showed that a low concentration of HCP1 decreased viral titer and viral load in BHK-21 and PK-15 cells, and 5μM HCP1 significantly decreased the expression of SVA VP2 protein. In addition, SVA infection can lead to an increased level of autophagy, and HCP1 can inhibit host cell autophagy caused by SVA infection, thereby inhibiting viral replication and infection. CONCLUSION:These findings reveal that Grp94 is a key factor in controlling SVA replication, and its inhibitor HCP1 suppresses SVA replication by inhibiting the increase of Grp94 protein level and autophagy induced by SVA. This study will contribute to the development of a new class of small-molecule antiviral drugs.

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non‐alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict‐normal thyroid function and low thyroid function groups (low‐normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results During a median follow‐up of 15.6 months, 165 (8.9%) strict‐normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22–1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47–2.60). Conclusions MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent.

Background: In terms of prostate biopsy approaches, it is difficult to reach the ventral central region of the prostate with the traditional transrectal prostate biopsy, while with the transperineal biopsy, the tumor in the dorsolateral region of the prostate is easily missed. However, until now, no studies have investigated the biopsy accuracy in the selective application of transrectal or transperineal biopsies according to the lesion site. Methods: We developed a personalized prostate biopsy pattern and the biopsy approach was selected individually according to the lesion site. We compared it with the traditional transrectal prostate biopsy method to evaluate the efficiency. Patients (n = 351) who underwent prostate biopsy at Qilu Hospital of Shandong University from January 2018 to October 2020 were divided into two groups, including the traditional transrectal prostate biopsy group (n = 236) and the personalized group (n = 115). The data from patients, including clinical characteristics, biopsy results, and complications, were analyzed. Results: The clinical characteristics of the two groups were similar. The total detection rate of prostate cancer in the personalized group was 49.6%, which was significantly higher than 38.1% in the traditional group (p = 0.023). When prostate-specific antigen was <20 ng/ml, the detection rates of the two groups were 30.4 and 19.3%, respectively (p = 0.039). The PI-RADS was positively associated with high-grade prostate cancer in the personalized group. Patients with complications in the traditional transrectal systematic method group accounted for 6.8%, and those in the personalized group complications through the transrectal and transperineal approaches accounted for 7.1 and 4.1%, respectively. The most common complications in the transrectal group were fever and rectal bleeding, and those in the transperineal group were hematuria and urinary retention. Conclusion: Compared with traditional transrectal prostate biopsy, the personalized biopsy pattern improved the detection rate of prostate cancer. The complications of the transrectal approach were much higher than those in the transperineal approach.

Background Risk models integrating new biomarkers to predict cardiovascular events in acute coronary syndromes (ACS) are lacking. Therefore, we evaluated the prognostic value of biomarkers in addition to clinical predictors and developed a biomarker-based risk model for major adverse cardiovascular events (MACE) within 12 months after hospital admission with ACS. Methods Patients (n = 4407) consecutively enrolled from November, 2017 to October, 2019 in three hospitals of a prospective Chinese registry (BIomarker-based Prognostic Assessment for Patients with Stable Angina and Acute Coronary Syndromes, BIPass) were designated as the risk model development cohort. Validation was performed in 1409 patients enrolled in two independent hospitals. Cox proportional hazards regression analysis was used to generate a risk prediction model and evaluate the incremental prognostic value of each biomarker. Findings Over 12 months, 196 patients experienced MACE (5.1%/year). Among twelve candidate biomarkers, N -terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline showed the most prognostic capability independent of clinical predictors. The developed BIPass risk model included age, hypertension, previous myocardial infarction, stroke, Killip class, heart rate, and NT-proBNP. It displayed improved discrimination (C-statistic 0.79, 95% CI 0.73-0.85), calibration (GOF = 9.82, p = 0.28) and clinical decision curve in the validation cohort, outperforming the GRACE and TIMI risk scores. Cumulative rates for MACE demonstrated good separation in the BIPass predicted low, intermediate, and high-risk groups. Interpretation The BIPass risk model, integrating clinical variables and NT-proBNP, is useful for predicting 12 month MACE in ACS. It effectively identifies a gradient risk of cardiovascular events to aid personalized care. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

BACKGROUND:Acute kidney injury (AKI) is still a critical problem in clinical practice, with a heavy burden for national health system around the world. It is notable that sepsis is the predominant cause of AKI for patients in the intensive care unit and the mortality remains considerably high. The treatment for AKI relies on supportive therapies and almost no specific treatment is currently available. Spermidine is a naturally occurring polyamine with pleiotropic effects. However, the renoprotective effect of spermidine and the underlying mechanism remain elusive.METHODS:We employed mice sepsis-induced AKI model and explored the potential renoprotective effect of spermidine in vivo with different administration time and routes. Macrophage depleting was utilized to probe the role of macrophage. In vitro experiments were conducted to examine the effect of spermidine on macrophage cytokine secretion, NLRP3 inflammasome activation and mitochondrial respiration.RESULTS:We confirmed that spermidine improves AKI with different administration time and routes and that macrophages serves as an essential mediator in this protective effect. Meanwhile, spermidine downregulates NOD-like receptor protein 3 (NLRP3) inflammasome activation and IL-1 beta production in macrophages directly. Mechanically, spermidine enhances mitochondrial respiration capacity and maintains mitochondria function which contribute to the NLRP3 inhibition. Importantly, we showed that eukaryotic initiation factor 5A (eIF5A) hypusination plays an important role in regulating macrophage bioactivity.CONCLUSIONS:Spermidine administration practically protects against sepsis-induced AKI in mice and macrophages serve as an essential mediator in this protective effect. Our study identifies spermidine as a promising pharmacologic approach to prevent AKI.

Myocardial ischemia/reperfusion (I/R) injury can bring about more cardiomyocyte death and aggravate cardiac dysfunction, but its pathogenesis remains unclear. This study aimed to investigate the role of long intergenic noncoding RNA-p21 (LincRNA-p21) in myocardial I/R injury and its underlying mechanism. Mice were subjected to myocardial I/R injury by ligation and release of the left anterior descending artery, and HL-1 cardiomyocytes were treated with hydrogen peroxide. Infarct area, cardiac function, and cardiomyocyte apoptosis were determined. Consequently, LincRNA-p21 was found to significantly be elevated both in the reperfused hearts and H2O2-treated cardiomyocytes. Moreover, genetic inhibition of LincRNA-p21 brought about reduced infarct area and improved cardiac function in mice subjected to myocardial I/R injury. LincRNA-p21 knockdown was also demonstrated to inhibit cardiomyocyte apoptosis both in vivo and in vitro. Notably, LincRNA-p21 silencing increased the expression of microRNA-466i-5p (miR-466i-5p) and suppressed the expression of nuclear receptor subfamily 4 group A member 2 (Nr4a2). Mechanically, LincRNA-p21 downregulated and directly interacted with miR-466i-5p, while application of miR-466i-5p inhibitor promoted cardiomyocyte apoptosis that was improved by LincRNA-p21 inhibition. Furthermore, Nr4a2 upregulation caused by LincRNA-p21 overexpression was partially reversed by miR-466i-5p mimics. Thus, LincRNA-p21 positively regulated the expression of Nr4a2, through sponging miR-466i-5p, promoting cardiomyocyte apoptosis in myocardial I/R injury. The current study revealed a novel LincRNA-p21/miR-466i-5p/Nr4a2 pathway for myocardial I/R injury, indicating that LincRNA-p21 may serve as a potential target for future therapy.

A 39 year-old young woman was referred to the cardiology department because of 'dizziness for 1 week'. She had a history of hypertension for 3 years, which was treated with irbesartan, but had poor blood pressure control for 1 week. The laboratory examination revealed an elevated renin level of 1000 uIU/ml. An enhanced computed tomography (CT) scan of the abdomen demonstrated a soft-tissue mass in the upper pole of the left kidney. The patient was admitted for further evaluation. Admission labs were notable for a serum potassium of 2.93 mmol/L. Blood pressure was elevated at 158/101 mmHg. A computed tomography angiography (CTA) examination of the renal vasculature (Fig. 1) was performed.

ABSTRACTTemperature‐sensitive hydrogels are attracting increasing attention for controlled drug delivery. However, achieving high drug loadings and sustained drug release remains challenging. Herein, we describe the successful synthesis of a series of novel temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPA)/mesoporous silica nanoparticles (MSN) hydrogels by physical crosslinking of NIPA with MSN. The external and internal structures, temperature sensitivity, drug‐loading capacity, and blood compatibility of the PNIPA/MSN composite hydrogels are studied. Results show that MSN addition improved the network structure and adjusted the size of the hole, MSN could also act as drug carrier, thereby enhancing the drug loading capacity. The composite hydrogels underwent a phase transition at 33.7 °C (at the lower critical solution temperature). The hemolysis rate of the composite hydrogels was less than 1%, thus they can be classified as a nonhemolytic materials with good biocompatibility. The composite hydrogels reported here thus have great potential in drug transport and temperature‐activated drug release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48391.

Purpose Several nephrometry scoring systems have been developed based on two-dimensional computerized tomography images to quantify anatomical features of renal tumors. We have developed an accurate three-dimensional nephrometry scoring system to respond to the urgent need for advanced systems based on three-dimensional images. Materials and Methods We retrospectively reviewed 135 patients who underwent partial nephrectomy in our institution. Stereoscopic models were reconstructed from preoperative computerized tomography images and three-dimensional scores were assigned directly on stereoscopic models. All tumors were analyzed for following features: tumor volume; endophytic tumor proportion; renal vascular variations; tumor’s relationships with urinary collecting system or renal sinus; longitudinal distance from tumor to equatorial plane. Correlation between three-dimensional score and warm ischemic time was calculated compared with existing classical nephrometry scoring systems. The value of nephrometry scoring systems predicting longer warm ischemic time was explored by receiver operating characteristic curves. Results Mean tumor volume was 31.25 ml; endophytic volume was less than 50% in 42 cases, more than 50% in 79 cases, and 100% in 14 cases; mean longitudinal distance from tumor to equatorial plane was 1.41 cm; 30 patients (22.2%) presented renal vascular variations; 18 cases (13.3%) involved both urinary collecting system and sinus. Mean three-dimensional score was 8.3. Variance analysis and covariance analysis revealed warm ischemic time a significant association with all evaluated tumor features. Furthermore, three-dimensional scores most highly correlated with warm ischemic time (rs = 0.64, p < 0.001), followed by R.E.N.A.L. scores (rs = 0.21, p = 0.012), centrality index (rs = − 0.20, p = 0.019) and Preoperative Aspects and Dimensions Used for Anatomy score (rs = 0.20, p = 0.019). Area under curve of above nephrometry scoring systems was 0.91, 0.67, 0.68 and 0.67 respectively (p < 0.05). Conclusions The three-dimensional scoring system developed in this study was a highly-accurate system to quantify the anatomical features of renal tumors. It was identified to have a value in predicting duration of warm ischemic time.

The accumulation of nonbiodegradable petrochemical-based polymers in the environment motivates the development and use of low-cost, eco-friendly, and biodegradable polymers. A series of biodegradable poly(butylene adipate-co-terephthalate) composites reinforced by sustainably sourced nanochitin were successfully prepared using melt blending and compression molding methods. Structural, thermal, and mechanical characterizations of poly(butylene adipate-co-terephthalate) (PBAT)/nanochitin composites were performed. SEM revealed that the nanochitin was uniformly dispersed throughout the PBAT matrix at low contents (<2 wt %), while DSC analyses revealed a corresponding increase in the crystallinity (32.6% enhancement) of the PBAT matrix. The tensile strength and elongation at break of the PBAT/nanochitin composite containing 0.5 wt % nanochitin were higher by 82.5 and 64.2%, respectively, compared with pristine PBAT. The Chitin-0.5 composite also showed improved thermal stability compared with PBAT (the char yield improved by 8%) due to the uniform dispersion of nanochitin in the PBAT matrix. The enhanced performance of the PBAT/nanochitin composites, prepared without an added compatibilizer, informs the development of improved biodegradable PBAT-based polymers. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48485.

Clear cell renal cell carcinoma (ccRCC) remains one of the most common cancer types globally, and while it has been extensively studied, the molecular basis for its pathology remains incompletely understood. Herein, we profiled three previously published datasets (GSE66272, GSE100666, and GSE105261) in a single integrated analysis aimed at identifying disease-associated patterns of gene expression that may offer mechanistic insight into the drivers of this disease. We pooled expression data from 39 normal kidney samples and 39 kidney tumors, leading us to identify 310 differentially expressed genes (DEGs) that were linked to kidney cancer in all three analyzed datasets. Of these genes, 133 and 177 were up- and down-regulated, respectively, in cancer samples. We then incorporated these DEGs into a protein-protein interaction network with the STRING and Cytoscape tools, and we were able to identify signaling pathways significantly enriched for these DEGs. The relationship between DEG expression and ccRCC patient survival was further evaluated using a Kaplan-Meier approach, leading us to identify TIMP1 as an independent prognostic factor in ccRCC patients. When TIMP1 expression was disrupted in ccRCC cell lines, this impaired their migratory and invasive capabilities. In summary, we employed an integrative bioinformatics approach to identify ccRCC-related DEGs and associated signaling pathways. Together these findings offer novel insight into the mechanistic basis for ccRCC, potentially helping to identify novel therapeutic targets for the treatment of this deadly disease.

Background Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property. Methods We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey's post hoc procedure by SPSS. Results The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model. Conclusions These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.

Post-cardiac arrest myocardial dysfunction significantly contributes to early mortality after the return of spontaneous circulation. However, no effective therapy is available now. Aldehyde dehydrogenase 2 (ALDH2) enzyme has been shown to protect the heart from aldehyde toxicity such as 4-hydroxy-2-nonenal (4-HNE) and oxidative stress. In this study, we evaluated the effect of enhanced activity or expression of ALDH2 on post-cardiac arrest myocardial dysfunction and survival in a rat cardiac arrest model. Furthermore, we elucidated the underlying mechanisms with a focus on mitochondrial reactive oxygen species (ROS) production in a cell hypoxia/reoxygenation model. A total of 126 rats were used for the ALDH2 activation or cardiac overexpression of ALDH2 studies. Randomization was done 10 min before the respective agonist injection or in vivo gene delivery. We showed that enhanced activity or expression of ALDH2 significantly improved contractile function of the left ventricle and survival rate in rats subjected to cardiac arrest-cardiopulmonary resuscitation procedure. Moreover, ALDH2 prevented cardiac arrest-induced cardiomyocyte death from apoptosis and mitochondrial damage. Mechanistically, 4-HNE, a representative substrate of ALDH2, was dominantly increased in the hypoxia/reoxygenation-exposed cardiomyocytes. Direct addition of 4-HNE led to significantly augmented succinate accumulation and mitochondrial ROS production. Through metabolizing 4-HNE, ALDH2 significantly inhibited mitochondrial ROS production. Our findings provide compelling evidence of the cardioprotective effects of ALDH2 and therapeutic targeting this enzyme would provide an important approach for treating post-cardiac arrest myocardial dysfunction.

Acute kidney injury (AKI) is a prevailing health threat around the world with high mortalities and heavy economic burdens.In the past, apoptosis was recognized as the main contributor to the pathogenesis of AKI.However, recent evidence has suggested that regulated necrosis also plays an important role in the pathologic process of various types of renal damages, improving our limited understanding of the complex mechanisms underlying AKI.Regulated necrosis is a newly identified type of "programed cell death" with morphologic features of necrosis, which includes necroptosis, ferroptosis, parthanatos, pyroptosis, etc.In this chapter, we summarized the molecular pathways of both apoptosis and regulated necrosis, and reviewed the potential roles and corresponding mechanisms of various cell deaths in AKI based on recent advances.We also discussed the therapeutic potentials and clinical implications based on manipulating regulated cell death.Taken together, the progress in this field lays the ground for better prevention and management of AKI in the future.

Background: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro. Methods: RSV was administered before renal ischemia and H2O2 induction. Serum and kidneys were harvested 24 h after reperfusion and NRK-52E cells were collected 4 h after H2O2 stimulation. Serum creatinine and blood urea nitrogen were used to assess renal function. Hematoxylin and eosin staining was performed to assess histological injury. Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to assess proinflammatory cytokine expression. Oxidative stress–related proteins, such as Nrf2 and TLR4, were evaluated by western blot. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling assay was used to detect apoptotic cells in tissues, and western blot was used to evaluate the expression of caspase-3, -8, and -9 in this study. Results: RSV inhibited inflammatory responses and improved renal function after renal IRI. Additionally, RSV decreased oxidative stress and reduced cell apoptosis by upregulating Nrf2 expression, downregulating the TLR4/NF-κB signaling pathway, and by decreasing caspase-3 activity and caspase cascades. Conclusion: Our study demonstrated the mechanisms underlying RSV renoprotection. We found that RSV exerts its greatest effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the Nrf2/TLR4/NF-κB pathway.

Herein, we report the successful synthesis of a series of poly (N-isopropylacrylamide) (PNIPA)/layered double hydroxides (LDHs)/nano-hydroxyapatite (nano-HA) hydrogels via in-situ radical polymerization. The internal morphology, thermo sensitivity, rheological properties, swelling behavior and hemocompatibility of the PNIPA/LDHs/HA composite hydrogels were systematically investigated. Results show that the hydrogels had a reversible sol-gel transformation around 33 °C. Interactions between the positively charged LDHs and negatively charged nano-HA particles created a highly porous hydrogel network. The composite hydrogels exhibited excellent hemocompatibility, incredible mechanical toughness and reversible swelling/deswelling behavior. To our knowledge, this is the first reported study to use two types of inorganic nanoparticle with opposing charges as hydrogel crosslinking agents. Based on its properties, we expect this hydrogel has broad applications potential in tissue engineering, drug delivery and biosensor development.

Injectable and thermosensitive poly(N-isopropylacrylamide) (PNIPA)/nano-hydroxyapatite (nano-HA) composite hydrogels were synthesized by physical crosslinking of N-isopropylacrylamide with nano-HA as cross-linker to improve the mechanical property of hydrogels and avoid the use of chemical cross-linker. Internal morphology, thermosensitive, rheological, swelling, and hemocompatibility properties of the prepared hydrogels were investigated. The PNIPA/HA composite hydrogels had a phase transition from sol to gel, and the lowest critical solution temperature was about 32.5 °C. The PNIPA/HA composite hydrogels had regular pore structures and the nano-HA dispersed well throughout the network. Differential scanning calorimetry and thermogravimetric analysis showed that the addition of nano-HA had no significant effect on the LCST and thermal stability of the PNIPA/HA hydrogels. When the temperature was above 32.5 °C, the storage modulus (G′) and complex viscosity increased with the increasing nano-HA content. All PNIPA/HA composite hydrogels possessed the thinning behavior. The PNIPA/HA hydrogels exhibited a good water absorption capacity and the swelling ratio decreased with the increasing nano-HA content. As revealed by biocompatibility results, PNIPA/HA composite hydrogels were considered to be a non-hemolytic biomaterial. Therefore, PNIPA/HA hydrogels can be used as injectable materials for the potential applications of science and technology, such as tissue engineering scaffolds.