PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.

INTRODUCTION: To investigate the role of a novel type of protein kinase C delta (PKCδ) in the neuroinflammation of Alzheimer's disease (AD). METHODS: We analyzed PKCδ and inflammatory cytokines levels in cerebrospinal fluid (CSF) of AD and normal controls, as well as their correlations. The cellular expression pattern of PKCδ and the effects of PKCδ modulation on microglia-mediated neuroinflammation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, RNA sequencing (RNA-seq), and immunofluorescence staining. RESULTS: PKCδ levels were increased dramatically in the CSF of AD patients and positively correlated with cytokines. PKCδ is expressed mainly in microglia in the brain. Amyloid beta (Aß) stimulation increased PKCδ expression and secretion, which led to upregulation of the nuclear factor kappa B (NF-κB) pathway and overproduction of proinflammatory cytokines. Downregulation or inhibition of PKCδ attenuated Aß-induced microglial responses and improved cognitive function in an AD mouse model. DISCUSSION: Our study identifies PKCδ as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD. HIGHLIGHTS: Protein kinase C delta (PKCδ) levels increase in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), and positively correlate with elevated inflammatory cytokines in human subjects. PKCδ is expressed mainly in microglia in vivo, whereas amyloid beta (Aß) stimulation increases PKCδ expression and secretion, causing upregulation of the nuclear factor kappa B (NF-κB) pathway and production of inflammatory cytokines. Downregulation or inhibition of PKCδ attenuates Aß-enhanced NF-κB signaling and cytokine production in microglia and improves cognitive function in AD mice. PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD.

Surface Tension-Induced Eccentric Hollow Polysiloxane Microspheres in a Surfactant-Free System and Their Applications as a Nanoreactor and Nanomotor.

Eccentric hollow polysiloxane microspheres (EHPMs) have attracted significant attention due to their potential in energy storage, drug delivery, and heterogeneous catalysis applications. However, their preparation pathways are often particularly complex. Therefore, it is critical to find a simple method for preparing EHPMs. In this study, a surfactant-free emulsification method is proposed to prepare EHPM. Under acidic conditions, methyl triethoxysilane (MTES) is hydrolyzed at the oil-water interface, with the hydrolyzed MTES demonstrating amphiphilic properties, and it could be anchored on the xylene surface to form an oil-in-water emulsion. The solution, when adjusted to alkaline, nucleated from a point at the oil-water interface. Driven by the surface tension, the hydrolyzed MTES migrated to the nucleation site with decreasing hydrophilicity. As a result, an EHPM formed. This process provides a simple, low cost, and environmentally friendly strategy for the preparation of EHPM, which demonstrated potential in catalytic and nanomotor applications.

Synthesis of 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition of nitrile imines with ninhydrin-derived Morita-Baylis-Hillman carbonates.

An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.

Optical Imaging in the Second Near Infrared Window for Vascular Bioimaging.

Optical imaging in the second near infrared region (NIR-II, 1000-1700 nm) provides higher resolution and deeper penetration depth for accurate and real-time vascular anatomy, blood dynamics, and function information, effectively contributing to the early diagnosis and curative effect assessment of vascular anomalies. Currently, NIR-II optical imaging demonstrates encouraging results including long-term monitoring of vascular injury and regeneration, real-time feedback of blood perfusion, tracking of lymphatic metastases, and imaging-guided surgery. This review summarizes the latest progresses of NIR-II optical imaging for angiography including fluorescence imaging, photoacoustic (PA) imaging, and optical coherence tomography (OCT). The development of current NIR-II fluorescence, PA, and OCT probes (i.e., single-walled carbon nanotubes, quantum dots, rare earth doped nanoparticles, noble metal-based nanostructures, organic dye-based probes, and semiconductor polymer nanoparticles), highlighting probe optimization regarding high brightness, longwave emission, and biocompatibility through chemical modification or nanotechnology, is first introduced. The application of NIR-II probes in angiography based on the classification of peripheral vascular, cerebrovascular, tumor vessel, and cardiovascular, is then reviewed. Major challenges and opportunities in the NIR-II optical imaging for vascular imaging are finally discussed.

Controlled Synthesis and Surface Engineering of Janus Chitosan-Gold Nanoparticles for Photoacoustic Imaging-Guided Synergistic Gene/Photothermal Therapy.

The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J-Au-CS) are selected as a model system to construct Janus-structured chitosan/gold nanohybrids (J-ACP). Near-infrared (NIR)-responsive J-ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging-guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J-ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT-enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging-guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.

Anion-Dependent Structure and Luminescence Diversity in ZnII-LnIII Heterometallic Architectures Supported by a Salicylamide-Imine Ligand.

To advance the structural development and fully explore the application potential, it is highly desirable but challenging to elucidate the relationship between the structures and properties of ZnII-LnIII heterometallic species. Herein, three types of ZnII-LnIII heterometallic compounds (LnIII = GdIII, TbIII) formulated as [Zn16Ln4L12(µ3-O)4(NO3)12]·8CH3CN (ZnLn-1), [Zn2Ln2L2(NO3)6(H2O)2]·3CH3CN (ZnLn-2), and [Zn4Ln2L8(OAc)12]·xCH3CN (ZnLn-3: for Ln = Gd, x = 5; for Ln = Tb, x = 4) were dictated by common inorganic anions, NO3- and OAc-, with the aid of the multidentate ligand H2L with propane as the central skeleton and 3-methoxysalicylamide and 3-methoxysalicylaldimine as terminal groups. ZnLn-1 features cubic cages with four {Zn4L3} tetrahedral subunits and four Ln3+ centers positioned at the eight vertices alternately when NO3- was introduced into the reaction system exclusively. An attempt to replace NO3- in ZnLn-1 with OAc- partially led to the formation of {Zn2Ln2L2} heterometallic wheels. Meanwhile, ZnLn-3 featuring double-hairpin-like {Zn4Ln2L4} hemicycles that are orthogonal to each other assisted by intermolecular hydrogen bonds was constructed when NO3- in ZnLn-1 was completely replaced by OAc-. Their structural integrity in solution were ascertained by both emission and 1H NMR spectroscopy. Ascribed to the different Zn2+-containing antenna, ZnTb-2 possesses a relatively strong emission characteristic of Tb3+; ZnTb-1 has moderate Tb3+ luminescence, yet an absence of Tb3+ emission is found in ZnTb-3. Such an emission difference could be mainly attributed to the antenna effect directed by distinct structural characteristics induced by anions. The anion-dictated self-assembly strategy presented herein not only offers a facile approach to regulate the coordination mode of H2L to such an extent to obtain diverse structures of ZnII-LnIII heterometallic species but also provides an understanding of how common inorganic anions tune coordination-driven self-assemblies as well as the subsequent luminescence properties.

Versatile Types of Organic/Inorganic Nanohybrids: From Strategic Design to Biomedical Applications.

Organic/inorganic nanohybrids have attracted widespread interests due to their favorable properties and promising applications in biomedical areas. Great efforts have been made to design and fabricate versatile nanohybrids. Among different organic components, diverse polymers offer unique avenues for multifunctional systems with collective properties. This review focuses on the design, properties, and biomedical applications of organic/inorganic nanohybrids fabricated from inorganic nanoparticles and polymers. We begin with a brief introduction to a variety of strategies for the fabrication of functional organic/inorganic nanohybrids. Then the properties and functions of nanohybrids are discussed, including properties from organic and inorganic parts, synergistic properties, morphology-dependent properties, and self-assembly of nanohybrids. After that, current situations of nanohybrids applied for imaging, therapy, and imaging-guided therapy are demonstrated. Finally, we discuss the prospect of organic/inorganic nanohybrids and highlight the challenges and opportunities for the future investigations.

Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthma.

BACKGROUND: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. METHODS: We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. RESULTS: In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran-Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/µl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017-2019 data as the internal validation dataset. CONCLUSION: FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/µl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging-Guided Synergistic Therapy.

Self-assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic-co-glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion-confined and polymer-directed self-assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid-modified R-PLGA-Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real-time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT-enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging-guided synergistic therapy.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Social inequality among elderly individuals caused by climate change: Evidence from the migratory elderly of mainland China.

Faced with severe and growing social inequality among elderly individuals, a more complete understanding of the interconnection between the seasonal migration of the elderly and climate change is clearly needed. This paper tries to clarify the relation between the seasonal migration of the elderly and climate change from a multidimensional perspective. Our study adds to the research on population aging against the background of climate change. This study shows that climate change has a significant impact on regional population aging and that there are significant internal differences between the distribution and scale of the migratory elderly stemming from unequal environmental conditions. Advanced economic conditions and relatively comfortable environments have put some pressure on social endowment services in the three provinces of Northeast China, especially Liaoning Province. With their complex migration mechanism, the fate of the elderly in mainland China is closely intertwined with climatic factors, individual and socioeconomic conditions, traditional cultural backgrounds, etc. A comparatively advanced economy, well-developed endowment resources, and a comfortable environment will help in the development of regional aging resources. Regional inequality and the pursuit of a meaningful life have created different categories of migratory elderly.

Organic/inorganic nanohybrids as multifunctional gene delivery systems.

In this review, we summarize the rational design and versatile application of organic/inorganic hybrid gene carriers as multifunctional delivery systems. Organic/inorganic nanohybrids with both organic and inorganic components in one nanoparticle have attracted intense attention because of their favorable properties. Particularly, nanohybrids comprising cationic polymers and inorganic nanoparticles are considered to be promising candidates as multifunctional gene delivery systems. In this review, we begin with an introduction of gene delivery and gene carriers to demonstrate the incentive for fabricating nanohybrids as multifunctional carriers. Next, the construction strategies and morphology effects of organic/inorganic hybrid gene carriers are summarized and discussed. Both sections provide valuable information for the design and synthesis of hybrid gene carriers with superior properties. Finally, an overview is provided of the application of nanohybrids as multifunctional gene carriers. Diverse therapies and versatile imaging-guided therapies have been achieved via the rational design of nanohybrids. In addition to a simple combination of the functions of organic and inorganic components, the performances arising from the synergistic effects of both components are considered to be more intriguing. In summary, this review might offer guidance for the understanding of organic/inorganic nanohybrids as multifunctional gene delivery systems.

Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.

Microenvironment-responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation-responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host-guest interaction of ß-cyclodextrin based polycations and a ferrocene-functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2 O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1 O2 ), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation-responsive nanoassemblies with light-enhanced gene transfection performance.

Blocking C/EBP ß protects vascular endothelial cells from injury induced by intermittent hypoxia.

BACKGROUND: Intermittent hypoxia (IH) can damage endothelial cells and lead to apoptosis in obstructive sleep apnea-hypopnea syndrome (OSAHS). Hypoxia induces apoptosis in endothelial cells via upregulation of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1α) plays a key role in the hypoxic stress response. PURPOSE: We investigated an approach to diminish the negative effect of HIF-1α while maintaining its protective effect. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to sustained hypoxia (SH) or IH for 24 h, and the responses of HIF-1α, CCAAT/enhancer binding protein beta (C/EBP ß), and endothelin-1 (ET-1) were assessed by western blotting. A luciferase reporter system was employed to verify the potential binding site (transcription factor binding site, TFBS) for C/EBP ß in the ET-1 promoter. The specificity of regulation of ET-1 by HIF-1α via C/EBP ß was evaluated by a lentiviral system. The effects of silencing of C/EBP ß on IH-induced apoptosis, vascular endothelial growth factor (VEGF) protein levels, proliferation, and in vitro tube formation were studied. RESULTS: We found that IH significantly increased HIF-1α, C/EBP ß, and ET-1 in HUVECs. Knockdown of HIF-1α or C/EBP ß inhibited the upregulation of ET-1 induced by IH. Blocking C/EBP ß impaired IH-induced apoptosis but did not affect VEGF expression, proliferation, or in vitro tube formation. C/EBP ß was shown to mediate increased ET-1 transcription by HIF-1α through the TFBS, 5'-GTTGCCTGTTG-3', in ET-1 promoter. CONCLUSION: Silencing of C/EBP ß can suppress apoptosis but does not affect the protective role of HIF-1α in the hypoxic stress response.

Urine volatile organic compounds as biomarkers for minimal change type nephrotic syndrome.

Urinary volatile organic compounds (VOCs) profiling has recently received considerable attention because it can be obtained noninvasively and conveniently while it can be successfully used in a variety of diseases and can provide unique biomarkers. The aim of current study was to investigate potential biomarkers between minimal change type nephrotic syndrome (MCNS) and normal. Urinary samples were collected from 38 minimal change type nephrotic syndrome patients and 15 healthy controls. Solid phase microextraction (SPME) and chromatography- mass spectrometry (GC-MS) were used to analysis the urinary metabolites. To deal with the final data, the statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed. Six specific VOC biomarkers were present at abnormal levels in the urine of MCNS patients. These VOCs included trans-2,2-dimethyl-4-decene; pyrrole; carbamic acid, monoammonium salt; 1-butyne, 3,3-dimethyl-; diisopropylamine; and 4-heptanone. These biomarkers may be useful as a new diagnostic method and for monitoring the prognosis for MCNS patients.

Flocculation performance of anionic starch in oil sand tailings.

A series of carboxymethyl starches (CMSs), with various degrees of substitution from 0.1 to 0.79, were synthesized and selected as a model to study the feasibility of using natural polymers as flocculants for oil sand tailings treatment. The flocculation performance of modified CMS in kaolin clay suspensions and oil sand tailings was evaluated in terms of settling rate, solids content, capillary suction time, and specific resistance to filtration of the sediment phase. It was found that the synthesized CMS effectively accelerates settling of kaolin suspensions and oil sand fine tailings, thus demonstrating the feasibility of this application.

NIR-Responsive Polycationic Gatekeeper-Cloaked Hetero-Nanoparticles for Multimodal Imaging-Guided Triple-Combination Therapy of Cancer.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke. Microglial macrophage-inducible C-type lectin (Mincle) receptor launches microglial innate immunity after SAH, and thereby achieves a key step of early cerebral injury in SAH. We previously revealed albumin could improve long-term neurological outcomes after SAH. In this study, we examined the role of microglia-mediated innate immunity in the salutary effects of albumin. SAH was induced by endovascular perforation in rats. We found that albumin can significantly mitigate early neurovascular dysfunction of SAH rats. Albumin administration resulted in reduced Iba-1 and CD68 staining in cortex. Markers of microglia M1 polarization (iNOS, IL-1ß, CD16, and CD32) were remarkably suppressed. Neutrophil invasion was inhibited as chemokines (MCP-1, CINC-1, and CXCL-2) mRNA levels, myeloperoxidase (MPO) and intracellular adhesion molecule-1 (ICAM-1) expressions were decreased. Mechanistically, albumin bound with microglial Mincle receptor, and retarded Mincle/Syk/IL-1ß signaling in ipsilateral hemisphere subjected to SAH. In the cultured BV-2 microglial cells, we found Mincle and its ligand SAP130 mediate the cross-talk between neuronal necroptosis and microglial immunity response following SAH-related injury. Albumin could attenuate SAP130-induced Mincle upregulation and subsequent microglial inflammatory responses. The anti-inflammation effect of albumin was similar to the effect of genetic knockdown of Mincle. This effect may be attributed to a direct association between albumin and Mincle. The interaction also yielded a depression in the initiation of Mincle/Syk/IL-1ß pathway. In conclusion, our results indicate that albumin can ameliorate innate immune responses after SAH. This anti-inflammatory action may be through direct restraining microglial Mincle receptor.

Multifunctional pDNA-Conjugated Polycationic Au Nanorod-Coated Fe3 O4 Hierarchical Nanocomposites for Trimodal Imaging and Combined Photothermal/Gene Therapy.

It is very desirable to design multifunctional nanocomposites for theranostic applications via flexible strategies. The synthesis of one new multifunctional polycationic Au nanorod (NR)-coated Fe3 O4 nanosphere (NS) hierarchical nanocomposite (Au@pDM/Fe3 O4 ) based on the ternary assemblies of negatively charged Fe3 O4 cores (Fe3 O4 -PDA), polycation-modified Au nanorods (Au NR-pDM), and polycations is proposed. For such nanocomposites, the combined near-infrared absorbance properties of Fe3 O4 -PDA and Au NR-pDM are applied to photoacoustic imaging and photothermal therapy. Besides, Fe3 O4 and Au NR components allow the nanocomposites to serve as MRI and CT contrast agents. The prepared positively charged Au@pDM/Fe3 O4 also can complex plasmid DNA into pDNA/Au@pDM/Fe3 O4 and efficiently mediated gene therapy. The multifunctional applications of pDNA/Au@pDM/Fe3 O4 nanocomposites in trimodal imaging and combined photothermal/gene therapy are demonstrated using a xenografted rat glioma nude mouse model. The present study demonstrates that the proper assembly of different inorganic nanoparticles and polycations is an effective strategy to construct new multifunctional theranostic systems.

Mechanical ventilation strategies for intensive care unit patients without acute lung injury or acute respiratory distress syndrome: a systematic review and network meta-analysis.

BACKGROUND: It has been shown that the application of a lung-protective mechanical ventilation strategy can improve the prognosis of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, the optimal mechanical ventilation strategy for intensive care unit (ICU) patients without ALI or ARDS is uncertain. Therefore, we performed a network meta-analysis to identify the optimal mechanical ventilation strategy for these patients. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published up to July 2015 in which pulmonary compliance or the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio was assessed in ICU patients without ALI or ARDS, who received mechanical ventilation via different strategies. The data for study characteristics, methods, and outcomes were extracted. We assessed the studies for eligibility, extracted the data, pooled the data, and used a Bayesian fixed-effects model to combine direct comparisons with indirect evidence. RESULTS: Seventeen randomized controlled trials including a total of 575 patients who received one of six ventilation strategies were included for network meta-analysis. Among ICU patients without ALI or ARDS, strategy C (lower tidal volume (VT) + higher positive end-expiratory pressure (PEEP)) resulted in the highest PaO2/FIO2 ratio; strategy B (higher VT + lower PEEP) was associated with the highest pulmonary compliance; strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay; and strategy D (lower VT + zero end-expiratory pressure (ZEEP)) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance. CONCLUSIONS: For ICU patients without ALI or ARDS, strategy C (lower VT + higher PEEP) was associated with the highest PaO2/FiO2 ratio. Strategy B (higher VT + lower PEEP) was superior to the other strategies in improving pulmonary compliance. Strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay, whereas strategy D (lower VT + ZEEP) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance.