Multifunctional Hierarchical Nanoplatform with Anisotropic Bimodal Mesopores for Effective Neural Circuit Reconstruction after Spinal Cord Injury.

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2-PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.

Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy.

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.

Spatially Asymmetric Nanoparticles for Boosting Ferroptosis in Tumor Therapy.

Despite its effectiveness in eliminating cancer cells, ferroptosis is hindered by the high natural antioxidant glutathione (GSH) levels in the tumor microenvironment. Herein, we developed a spatially asymmetric nanoparticle, Fe3O4@DMS&PDA@MnO2-SRF, for enhanced ferroptosis. It consists of two subunits: Fe3O4 nanoparticles coated with dendritic mesoporous silica (DMS) and PDA@MnO2 (PDA: polydopamine) loaded with sorafenib (SRF). The spatial isolation of the Fe3O4@DMS and PDA@MnO2-SRF subunits enhances the synergistic effect between the GSH-scavengers and ferroptosis-related components. First, the increased exposure of the Fe3O4 subunit enhances the Fenton reaction, leading to increased production of reactive oxygen species. Furthermore, the PDA@MnO2-SRF subunit effectively depletes GSH, thereby inducing ferroptosis by the inactivation of glutathione-dependent peroxidases 4. Moreover, the SRF blocks Xc- transport in tumor cells, augmenting GSH depletion capabilities. The dual GSH depletion of the Fe3O4@DMS&PDA@MnO2-SRF significantly weakens the antioxidative system, boosting the chemodynamic performance and leading to increased ferroptosis of tumor cells.

Nanoparticles with transformable physicochemical properties for overcoming biological barriers.

In recent years, tremendous progress has been made in the development of nanomedicines for advanced therapeutics, yet their unsatisfactory targeting ability hinders the further application of nanomedicines. Nanomaterials undergo a series of processes, from intravenous injection to precise delivery at target sites. Each process faces different or even contradictory requirements for nanoparticles to pass through biological barriers. To overcome biological barriers, researchers have been developing nanomedicines with transformable physicochemical properties in recent years. Physicochemical transformability enables nanomedicines to responsively switch their physicochemical properties, including size, shape, surface charge, etc., thus enabling them to cross a series of biological barriers and achieve maximum delivery efficiency. In this review, we summarize recent developments in nanomedicines with transformable physicochemical properties. First, the biological dilemmas faced by nanomedicines are analyzed. Furthermore, the design and synthesis of nanomaterials with transformable physicochemical properties in terms of size, charge, and shape are summarized. Other switchable physicochemical parameters such as mobility, roughness and mechanical properties, which have been sought after most recently, are also discussed. Finally, the prospects and challenges for nanomedicines with transformable physicochemical properties are highlighted.

Emerging enzyme-based nanocomposites for catalytic biomedicine.

With the promising advances in nanomedicine, numerous strategies have emerged for the diagnosis and treatment of diseases. Among them, enzyme-based multifunctional nanocomposites have attracted a great deal of attention in the field of catalytic biomedicine. These nanocomposites with high catalytic activity are capable of converting low/non-toxic substances into therapeutic ones, thus realizing highly efficient, site-specific therapy with minimal side effects. Enzyme-based nanocomposites for catalytic biomedicine are mainly divided into three types: (i) natural-enzyme based nanocomposites; (ii) artificial-nanozyme based nanocomposites; and (iii) nanocomposites of natural-enzymes and nanozymes. In this review, we discuss key aspects of enzyme-based catalytic biomedicine, including the construction of enzyme-based nanocomposites, their unique properties and applications in catalytic biomedicine. We also highlight the main challenges faced in this field, and provide relevant guidelines for the rational design and extensive application of enzyme-based nanocomposites from our point of view.

Versatile synthesis of metal-compound based mesoporous Janus nanoparticles.

The construction of mesoporous Janus nanoparticles (mJNPs) with controllable components is of great significance for the development of sophisticated nanomaterials with synergistically enhanced functionalities and applications. However, the compositions of reported mJNPs are mainly the functionally inert SiO2 and polymers. The universal synthesis of metal-compound based mJNPs with abundant functionalities is urgently desired, but remains a substantial challenge. Herein, we present a hydrophilicity mediated interfacial selective assembly strategy for the versatile synthesis of metal-compound based mJNPs. Starting from the developed silica-based mJNPs with anisotropic dual-surface of hydrophilic SiO2 and hydrophobic organosilica, metal precursor can selectively deposit onto the hydrophilic SiO2 subunit to form the metal-compound based mJNPs. This method shows good universality and can be used for the synthesis of more than 20 kinds of metal-compound based mJNPs, including alkali-earth metal compounds, transition metal compounds, rare-earth metal compounds etc. Besides, the composition of the metal-compound subunit can be well tuned from single to multiple metal elements, even high-entropy complexes. We believe that the synthesis method and obtained new members of mJNPs provide a very broad platform for the construction and application of mJNPs with rational designed functions and structures.

Site-specific anisotropic assembly of amorphous mesoporous subunits on crystalline metal-organic framework.

As an important branch of anisotropic nanohybrids (ANHs) with multiple surfaces and functions, the porous ANHs (p-ANHs) have attracted extensive attentions because of the unique characteristics of high surface area, tunable pore structures and controllable framework compositions, etc. However, due to the large surface-chemistry and lattice mismatches between the crystalline and amorphous porous nanomaterials, the site-specific anisotropic assembly of amorphous subunits on crystalline host is challenging. Here, we report a selective occupation strategy to achieve site-specific anisotropic growth of amorphous mesoporous subunits on crystalline metal-organic framework (MOF). The amorphous polydopamine (mPDA) building blocks can be controllably grown on the {100} (type 1) or {110} (type 2) facets of crystalline ZIF-8 to form the binary super-structured p-ANHs. Based on the secondary epitaxial growth of tertiary MOF building blocks on type 1 and 2 nanostructures, the ternary p-ANHs with controllable compositions and architectures are also rationally synthesized (type 3 and 4). These intricate and unprecedented superstructures provide a good platform for the construction of nanocomposites with multiple functionalities and understanding of the structure-property-function relationships.

Camouflaged Virus-Like-Nanocarrier with a Transformable Rough Surface for Boosting Drug Delivery.

Due to non-specific strong nano-bio interactions, it is difficult for nanocarriers with permanent rough surface to cross multiple biological barriers to realize efficient drug delivery. Herein, a camouflaged virus-like-nanocarrier with a transformable rough surface is reported, which is composed by an interior virus-like mesoporous SiO2 nanoparticle with a rough surface (vSiO2 ) and an exterior acid-responsive polymer. Under normal physiological pH condition, the spikes on vSiO2 are hidden by the polymer shell, and the non-specific strong nano-bio interactions are effectively inhibited. While in the acidic tumor microenvironment, the nanocarrier sheds the polymer camouflage to re-expose its rough surface. So, the retention ability and endocytosis efficiency of the nanocarrier are great improved. Owing to it's the dynamically variable rough surface, the rationally designed nanocarrier exhibits extended blood-circulation-time and enhanced tumor accumulation.

Versatile synthesis of dendritic mesoporous rare earth-based nanoparticles.

Rare earth-based nanomaterials that have abundant optical, magnetic, and catalytic characteristics have many applications. The controllable introduction of mesoporous channels can further enhance its performance, such as exposing more active sites of rare earth and improving the loading capacity, yet remains a challenge. Here, we report a universal viscosity-mediated assembly strategy and successfully endowed rare earth-based nanoparticles with central divergent dendritic mesopores. More than 40 kinds of dendritic mesoporous rare earth-based (DM-REX) nanoparticles with desired composition (single or multiple rare earth elements, high-entropy compounds, etc.), particle diameter (80 to 500 nanometers), pore size (3 to 20 nanometers), phase (amorphous hydroxides, crystalline oxides, and fluorides), and architecture were synthesized. Theoretically, a DM-REX nanoparticle library with 393,213 kinds of possible combinations can be constructed on the basis of this versatile method, which provides a very broad platform for the application of rare earth-based nanomaterials with rational designed functions and structures.

Influenza A(H7N9) virus emerged and resulted in human infections in Chongqing, southwestern China since 2017.

OBJECTIVES: Influenza A(H7N9) virus has emerged and resulted in human infections in Chongqing, southwestern China since 2017. This study aimed to describe the epidemiological characteristics of the first epidemic in this region. METHODS: The epidemiological data of patients were collected. Live poultry markets (LPMs), commercial poultry farms (CPFs) and backyard poultry farms (BPFs) were monitored, and poultry sources were registered. Samples derived from the patients, their close contacts, and the environments were tested for influenza A(H7N9) virus by real-time reverse transcriptase polymerase chain reaction. Genetic sequencing and phylogenetic analysis were also conducted. RESULTS: Since the confirmation of the first patient infected with influenza A(H7N9) virus on March 5, 2017, nine patients had been identified within four months in Chongqing. Their mean age was 45 years, 77.8% were male, 66.7% were urban residents and 55.6% were of poultry related occupation. All patients became infected after exposure to live chickens. The median time interval from initial detection of influenza A(H7N9) virus in Chongqing to the patients' onset was 75 days. Since initial detection in February 2017, influenza A(H7N9) virus was detected in 21 (53.8%) counties within four months. The proportion of positive samples was 2.94% (337/11,451) from February 2017 to May 2018, and was higher (χ2=75.78, P<0.001) in LPMs (3.66%, 329/8979) than that in CPFs (0.41%, 5/1229) and BPFs (0.24%, 3/1243). The proportion of positive samples (34.4%, 22/64) at the premises to which the patients were exposed was significantly higher than that (5.7%, 257/4474) in premises with no patients. Phylogenetic analysis indicated that the viruses isolated in Chongqing belonged to the Yangtze River Delta lineage and resembled those circulated in Jiangsu and Anhui provinces between late 2016 and early 2017. CONCLUSION: Influenza A(H7N9) virus was newly introduced into Chongqing most likely between late 2016 and early 2017, which swept across half of Chongqing territory and resulted in human infections within months. The most impacted premises and population were LPMs and poultry related workers respectively in the epidemic.

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats.

BACKGROUND & AIMS: Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. METHODS: A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. RESULTS: We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load. CONCLUSION: In summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance.

[Comparison of the influences of gold alloy metal crown and ni-cr alloy metal crown on gingival health].

OBJECTIVE: To compare the influences of gold alloy metal crown and Ni-Cr alloy metal crown on gingival health. METHODS: Totally 20 patients requiring one metal crown restoration were divided into the gold alloy metal crown group (n=9) and Ni-Cr alloy metal crown group (n=11). The contra-lateral homonymy natural healthy teeth served as controls. Before the tooth preparation and 6 months after crown placement, the weight of gingival crevicular fluid (GCF) of each tooth (included the test teeth and the control teeth) was measured, and the probing depth and the sulcus bleeding index of each tooth were also recorded. RESULTS: In the gold alloy metal crown group, the weight of GCF detected before the tooth preparation was significantly larger than that detected 6 months after restoration (P<0.05). In the Ni-Cr alloy metal crown group, the sulcus bleeding index recorded 6 months after restoration was significantly larger than that recorded before the tooth preparation (P<0.05). The other experimental indicators were not significantly different before and after restoration. CONCLUSION: The gold alloy metal crowns will not cause obvious harm to the periodontal tissues of the abutments shortly after restoration, while the Ni-Cr alloy metal crowns may increase the risk of sulcus bleeding.