A "Dual-Key-and-Lock" MRI Contrast Agent with T1-T2 Switchable Function for Accurate Diagnosis of Tumors.

Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T1 to T2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.

Deciphering the Temporal-Spatial Interactive Heterogeneity of Long Non-Coding RNAs and RNA-Binding Proteins in Living Cells at Single-Cell Resolution.

The investigation of long noncoding RNAs (lncRNAs) and RNA binding proteins (RBPs) interactions in living cell holds great significance for elucidating their critical roles in a variety of biological activities, but limited techniques are available to profile the temporal-spatial dynamic heterogeneity. Here, we introduced a molecular beacon-functionalized nanoneedle array designed for spatially resolved profiling of lncRNA-RBP interactions (Nano-SpatiaLR). A nanoneedle array modified with a molecular beacon is employed to selectively isolate specific intracellular lncRNAs and their associated RBPs without affecting cell viability. The RBPs are then in situ analyzed with a fluorescent labeled antibody and colocalized with lncRNA signals to get a quantitative measurement of their dynamic interactions. Additionally, leveraging the spatial distribution and nanoscale modality of the nanoneedle array, this technique provides the spatial heterogeneity information on cellular lncRNA-RBPs interaction at single cell resolution. In this study, we tracked the temporal-spatial interactive heterogeneity dynamics of lncRNA-RBPs interaction within living cells across different biological progresses. Our findings demonstrated that the interactions between lncRNA HOTAIR and RBPs EZH2 and LSD1 undergo significant changes in response to drug treatments, particularly in tumor cells. Moreover, these interactions become more intensified as tumor cells aggregate during the proliferation process.

HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Flexible light-stimulated artificial synapse based on detached (In,Ga)N thin film for neuromorphic computing.

Because of wide range of applications, the flexible artificial synapse is an indispensable part for next-generation neural morphology computing. In this work, we demonstrate a flexible synaptic device based on a lift-off (In,Ga)N thin film successfully. The synaptic device can mimic the learning, forgetting, and relearning functions of biological synapses at both flat and bent states. Furthermore, the synaptic device can simulate the transition from short-term memory to long-term memory successfully under different bending conditions. With the high flexibility, the excitatory post-synaptic current of the bent device only shows a slight decrease, leading to the high stability. Based on the experimental conductance for long-term potentiation and depression, the simulated three-layer neural network can achieve a high recognition rate up to 90.2%, indicating that the system comprising of flexible synaptic devices could have a strong learning-memory capability. Therefore, this work has a great potential for the development of wearable intelligence devices and flexible neuromorphic systems.

Dengue determinants: Necessities and challenges for universal dengue vaccine development.

Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.

Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy.

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.

Dual Signal Amplification by Urease Catalysis and Silver Nanoparticles for Ultrasensitive Colorimetric Detection of Nucleic Acids.

Signal amplification techniques are highly desirable for the analysis of low-level targets that are closely related with diseases and the monitoring of important biological processes. However, it is still challenging to achieve this goal in a facile and economical way. Herein, we developed a novel dual signal amplification strategy by combining urease catalysis with the release of Ag+ from silver nanoparticles (AgNPs). This strategy was used for quantifying a DNA sequence (HIV-1) related with human immunodeficiency virus (HIV). DNA target HIV-1 hybridizes with the capture DNA probe on magnetic beads and the reporter DNA probe on AgNPs, forming a sandwich complex. The captured AgNPs are then transformed into numerous Ag+ ions that inactivate numerous ureases. Without catalytic production of ammonia from urea, the substrate solution shows a low pH 5.8 that will increase otherwise. The pH change is monitored by a pH indicator (phenol red), which allows for colorimetric detection. The proposed approach is sensitive, easy to use, economic, and universal, exhibiting a low detection limit of 9.7 fM (i.e., 1.94 attomoles) and a dynamic linear range of 4 orders for HIV-1 sequence detection.

Perovskite-Type Manganese Vanadate Sonosensitizers with Biodegradability for Enhanced Sonodynamic Therapy of Cancer.

Sonodynamic therapy (SDT) has attracted intensive attention, but is still hindered by low sonosensitization and non-biodegradability of the traditional sonosensitizers. Herein, perovskite-type manganese vanadate (MnVO3 ) sonosensitizers integrating high reactive oxide species (ROS) production efficiency and appropriate bio-degradability are developed for enhanced SDT. Taking advantage of the intrinsic properties of perovskites such as narrow bandgap and substantial oxygen vacancies, MnVO3 shows a facile ultrasound (US)-triggered electrons-holes separation and restrained recombination, thus enhancing the ROS quantum yield in SDT. Furthermore, MnVO3 exhibits a considerable chemodynamic therapy (CDT) effect under the acidic condition probably owing to the presence of manganese and vanadium ions. Due to the presence of high-valent vanadium, MnVO3 can also eliminate glutathione (GSH) within the tumor microenvironment, which synergistically amplifies the efficacy of SDT and CDT. Importantly, the perovskite structure bestows MnVO3 with superior biodegradability, which alleviates the long-term presence of residues in metabolic organs after therapeutic actions. Based on these characteristics, US-assisted MnVO3 achieves an excellent antitumor outcome along with low systemic toxicity. Overall, perovskite-type MnVO3 may be promising sonosensitizers for highly efficient and safe treatment of cancer. The work attempts to explore the potential utility of perovskites in the design of degradable sonosensitizers.

Efficacy of IVIG therapy for patients with sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality. It requires urgent interventions in order to improve outcomes. Intravenous immunoglobulins (IVIG) are considered as potential therapy in sepsis patients. Results of trials on IVIG as adjunctive therapy for sepsis have been conflicting due to the variability in population characteristics, country geography and drug dosage form in different studies. METHODS: A systematic article search was performed for eligible studies published up to January, 31, 2023, through the PubMed, Embase, Cochrane Library and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. Subgroup analyses were conducted according to different IVIG types, ages and economic regions. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. RESULTS: In total, 31 randomized controlled trials were included with a sample size of 6,276 participants. IVIG could reduce the mortality (RR 0.86, 95% CI: 0.77-0.95, p = 0.005), the hospital stay (MD - 4.46, 95% CI: - 6.35 to - 2.57, p = 0.00001), and the APACHE II scores (MD - 1.65, 95% CI: - 2.89 to - 0.63, p = 0.001). Additionally, the results showed that IgM-enriched IVIG was effective in treating sepsis (RR 0.55, 95% CI: 0.40 - 0.76; p = 0.0003), while standard IVIG failed to be effective (RR 0.91, 95% CI: 0.81-1.02, p = 0.10). And the effect of IVIG in reducing neonatal mortality was inconclusive (RR 0.93, 95% CI: 0.81-1.05, p = 0.24), but it played a large role in reducing sepsis mortality in adults (RR 0.70, 95% CI: 0.57-0.86, p = 0.0006). Besides, from the subgroup of different economic regions, it indicated that IVIG was effective for sepsis in high-income (RR 0.89, 95% CI: 0.79-0.99, p = 0.03) and middle-income countries (RR 0.49, 95% CI: 0.28-0.84, p = 0.01), while no benefit was demonstrated in low-income countries (RR 0.56, 95% CI: 0.27-1.14, p = 0.11). CONCLUSIONS: There is sufficient evidence to support that IVIG reduces sepsis mortality. IgM-enriched IVIG is effective in both adult and neonatal sepsis, while standard IVIG is only effective in adult sepsis. IVIG for sepsis has shown efficacy in high- and middle-income countries, but is still debatable in low-income countries. More RCTs are needed in the future to confirm the true clinical potential of IVIG for sepsis in low-income countries.

Hypoxia-Responsive T2-to-T1 Dynamically Switchable Extremely Small Iron Oxide Nanoparticles for Sensitive Tumor Imaging In Vivo.

To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T1 and T2 contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T2-to-T1-switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4'-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T2-to-T1-switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the r2/r1 ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T2 to T1 contrast enhancement. This T2-to-T1-switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.

Interpenetrating Polymer Network HA/Alg-RGD Hydrogel: An Equilibrium of Macroscopic Stability and Microscopic Adaptability for 3D Cell Growth and Vascularization.

Two-dimensional (2D) cell culture methods dominate the current research. However, the inherent responsiveness of cells to their native three-dimensional (3D) microenvironment necessitates a paradigm shift toward the development of advanced hydrogels that faithfully mimic the intricacies of the extracellular matrix (ECM) and enable continuous cell-ECM interactions. To address the constraints of traditional static hydrogel networks that impede effective cell-matrix and cell-cell interactions, and to tackle the inherent stability issues associated with dynamically cross-linked hydrogels, which have become a pressing concern. Herein, we present an interpenetrating polymer network (IPN) hydrogel (HA/Alg-RGD hydrogel) that combines a physically cross-linked network between alginate and calcium ions (Alg-Ca2+) for the enhanced cell growth adaptability with a chemically cross-linked hyaluronic acid (HA) network to ensure macroscopic stability during cell culture. The incorporation of arginine-glycine-aspartic peptide modified alginate (Alg-RGD) further facilitates cell adhesion and improves the cell-hydrogel interaction. Notably, this IPN hydrogel demonstrates mechanical stability and enables cell spreading and growth within its structural framework. Leveraging the reversible characteristics of the ionically cross-linked Alg-Ca2+ network within IPN hydrogels, we demonstrate the feasibility of the gelatin sacrificial solution for 3D printing purposes within the hydrogel matrix. Subsequent UV-induced covalent cross-linking enables the fabrication of vascularized microfluidic channels within the resulting construct. Our results demonstrate endothelial cell spreading and spontaneous cell sprouting within the hydrogel matrix, thus highlighting the efficacy of this IPN hydrogel system in facilitating 3D cell growth. Additionally, our study emphasizes the potential of 3D printed constructs as a promising approach for vascularization in tissue engineering. The importance of RGD peptides in promoting favorable cell-hydrogel scaffold interactions is also highlighted, emphasizing their critical role in optimizing biomaterial-cell interfaces.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

Antibody Assay and Anti-Inflammatory Function Evaluation of Therapeutic Potential of Different Intravenous Immunoglobulins for Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against ß-amyloid (Aß)42, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aß42/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.

Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting.

Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. Here, we develop a novel circulating tumor cell (CTC)-based transcriptomic profiling assay to translate tissue-based messenger RNA (mRNA) signatures into a liquid biopsy setting for noninvasive HCC prognostication. The HCC-CTC mRNA scoring system combines the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC Risk Score (RS) panel in enriched HCC CTCs. The prognostic role of the HCC-CTC RS was assessed in The Cancer Genome Atlas (TCGA) HCC cohort (n = 362) and validated in an independent clinical CTC cohort (n = 40). The HCC-CTC RS panel was developed through our integrated data analysis framework of 8 HCC tissue-based gene signatures and identified the top 10 prognostic genes (discoidin domain receptor tyrosine kinase 1 [DDR1], enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase [EHHADH], androgen receptor [AR], lumican [LUM], hydroxysteroid 17-beta dehydrogenase 6[HSD17B6], prostate transmembrane protein, androgen induced 1 [PMEPA1], tsukushi, small leucine rich proteoglycan [TSKU], N-terminal EF-hand calcium binding protein 2 [NECAB2], ladinin 1 [LAD1], solute carrier family 27 member 5 [SLC27A5]) highly expressed in HCC with low expressions in white blood cells. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.9). The combined use of the scoring system and HCC-CTC RS panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P = 0.02). In the CTC validation cohort (n = 40), HCC-CTC RS remained an independent predictor of survival (HR, 5.7; 95% CI, 1.5-21.3; P = 0.009) after controlling for Model for End-Stage Liver Disease score, Barcelona Clinic Liver Cancer stage, and CTC enumeration count. Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This noninvasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

Recent progress on adsorption of cadmium ions from water systems using metal-organic frameworks (MOFs) as an efficient class of porous materials.

Various articles have been written about MOFs, which are organic-inorganic polymer structures that are unique in three-dimensional porosity, crystalline structure, and their ability to adsorb cadmium ion pollutants from aqueous solutions. These materials possess active metal sites, highly porous structures, high specific surfaces, high chemical functionality, and porous topologies. It is necessary to study adsorption kinetics, isotherms, and mechanisms in order to better understand the adsorption process. Adsorption kinetics can provide information about the adsorption rate and reaction pathway of adsorbents. Adsorption isotherms analyze the possibility of absorbances based on the Gibbs equation and thermodynamic theories. Moreover, in practical applications, knowledge of the adsorption mechanism is essential for predicting adsorption reactions and designing MOFs structures. In this review, the latest suggested adsorption mechanisms, kinetics, and isotherms of MOFs-based materials for removing cadmium ions are presented. A comparison is then conducted between different MOFs and the mechanisms of cadmium ion removal. We also discuss the future role of MOFs in removing environmental contaminants. Lastly, we discuss the gap in research and limitations of MOFs as adsorbents in actual applications, and probable technology development for the development of cost-efficient and sustainable MOFs for metal ion removal.

In Situ Forming Cellulose Nanofibril-Reinforced Hyaluronic Acid Hydrogel for Cartilage Regeneration.

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.

The isolation of a DNA aptamer to develop a fluorescent aptasensor for the thiamethoxam pesticide.

Aptamers, which are called chemical antibodies for their high affinity and specificity to targets, have great potential as analytical tools to detect pesticides. In this work, a DNA aptamer for thiamethoxam was isolated by an improved SELEX (systematic evolution of ligands by exponential enrichment) strategy, in which the ssDNA library was fixed on streptavidin-agarose beads through a short biotin labeled complementary strand. After 13 rounds of selection, the random ssDNA pool was successfully enriched. Three sequences were chosen as aptamer candidates through sequencing and analysis and were transformed into fluorescent probes to evaluate their interactions with thiamethoxam. A fluorescent turn-on aptasensor for thiamethoxam based on the best aptamer (FAM-Thi13) and a short quenching strand were further designed and showed a quantitative linear range from 10 to 1000 nM with a detection limit of 1.23 nM for thiamethoxam. Molecular docking and molecular dynamics were used to investigate the binding site of the main probe of the aptasensor (FAM-Thi13) and thiamethoxam. Satisfactory results were also obtained in quantifying thiamethoxam in environmental water samples by the developed fluorescent aptasensor.

NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer.

BACKGROUND: Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. METHODS: Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. RESULTS: The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. CONCLUSION: A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.

Micron-Sized Ultrathin Metal-Organic Framework Sheet.

The two-dimensional thin metal-organic frameworks (MOF) sheet has emerged as a promising hybrid material for applications in catalysis and optoelectronic devices. However, the small size and large thickness of an MOF sheet still pose barriers toward its potential applications. Herein, a micron-sized ultrathin MOF sheet is synthesized with the assistance of benzoic acid. Benzoic acid promoted the coordination of the porphyrin center with copper ions, reduced H-stacking and J-aggregation between the layers, and induced anisotropic growth of the MOF sheet. The results reveal the growth mechanism and provide a viable method for the synthesis of ultrathin MOF sheet. The as-prepared micron-sized ultrathin MOF sheet has good dispersion and high stability, which can ensure the long-term application properties of this material. The ultrathin thickness in combination with its micron size can make MOF as useful as graphene in practical applications. The synthesis of a micron-sized ultrathin MOF sheet similar to the thickness of graphene can pave the way for effective applications of two-dimensional MOF materials.

3D Bioprinting of Bone Marrow Mesenchymal Stem Cell-Laden Silk Fibroin Double Network Scaffolds for Cartilage Tissue Repair.

3D bioprinting is one of the latest trends in regenerative medicine due to its capacity for constructing highly organized tissues with living cells. In this work, silk fibroin (SF) together with hydroxypropyl methyl cellulose (HPMC) was used to print bone marrow mesenchymal stem cell (BMSC)-laden double network (DN) hydrogel for cartilage tissue repair. The ß-sheet structure formed among SF molecules was set as the rigid and brittle first network, while the cross-linking of HPMC-MA was set as the soft and ductile second network. Compared to the single network hydrogel, the fracture strength, breaking elongation, and compressive reproducibility increased significantly. Thereafter, the evaluation of cell proliferation and biochemical assay of this BMSC-laden 3D bioprinted hydrogel proved that it could ensure sufficient nutrient supply and great biochemical supportability in tissue engineering. This SF-based bioink with remarkable mechanical properties holds great promise as candidate for cartilage tissue regeneration.