Cobalt protoporphyrin-induced nano-self-assembly for CT imaging, magnetic-guidance, and antioxidative protection of stem cells in pulmonary fibrosis treatment.

Mesenchymal stem cells (MSCs) transplantation is a promising approach for pulmonary fibrosis (PF), however it is impeded by several persistent challenges, including the lack of long-term tracking, low retention, and poor survival of MSCs, as well as the low labeling efficiency of nanoprobes. Herein, a cobalt protoporphyrin IX (CoPP) aggregation-induced strategy is applied to develop a multifunctional nano-self-assembly (ASCP) by combining gold nanoparticle (AuNPs), superparamagnetic iron oxide nanoparticles (SPIONs), and CoPP through a facile solvent evaporation-driven approach. Since no additional carrier materials are employed during the synthesis, high loading efficiency of active ingredients and excellent biocompatibility are achieved. Additionally, facile modification of the ASCPs with bicyclo[6.1.0]nonyne (BCN) groups (named as ASCP-BCN) enables them to effectively label MSCs through bioorthogonal chemistry. The obtained ASCP-BCN could not only help to track MSCs with AuNP-based computed tomography (CT) imaging, but also achieve an SPIONs-assisted magnetic field based improvement in the MSCs retention in lungs as well as promoted the survival of MSCs via the sustained release of CoPP. The in vivo results demonstrated that the labeled MSCs improved the lung functions and alleviated the fibrosis symptoms in a bleomycin-induced PF mouse model. Collectively, a novel ASCP-BCN multifunctional nanoagent was developed to bioorthogonally-label MSCs with a high efficiency, presenting a promising potential in the high-efficient MSC therapy for PF.

An Endogenous H2S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer.

Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of •OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.

Microfluidics-Assisted Engineering of pH/Enzyme Dual-Activatable ZIF@Polymer Nanosystem for Co-Delivery of Proteins and Chemotherapeutics with Enhanced Deep-Tumor Penetration.

The impermeable barriers of solid tumors restrict the co-delivery of protein-based drugs and chemotherapeutics for cancer treatment. Therefore, we developed a ZIF-DOX/RA@DG nanosystem that encapsulates ribonuclease A (RA) and doxorubicin (DOX) in a zeolitic imidazolate framework (ZIF-8) core, with a dextran-based coating (DG). The nanosystem exhibits dual-responsiveness due to γ-glutamyl transpeptidase-activatable cationization and acidic microenvironment-triggered degradation. The DG-coating process was achieved using a microfluidic approach, which stabilized the polymer responsiveness, ZIF-8-based structure, and bioactivity of the encapsulated therapeutics. In vivo results confirmed that the nanosystem could co-deliver RA and DOX to deep impermeable lesions with a synergistic anticancer therapeutic effects. Such a multi-drug delivery system based on an intelligent-responsive design and a microfluidics-assisted synthesis strategy shows great clinical prospects.

Reshaping the Tumor Immune Microenvironment Based on a Light-Activated Nanoplatform for Efficient Cancer Therapy.

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO3 /Bi2 WO6 (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h+ )-electron (e- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h+ can trigger the decomposition of H2 O2 to generate O2 for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O2 self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.

Microfluidics-Assisted Surface Trifunctionalization of a Zeolitic Imidazolate Framework Nanocarrier for Targeted and Controllable Multitherapies of Tumors.

Metal-organic framework (MOF)-based drug delivery nanosystems with both precise drug release and multidrug codelivery capabilities have emerged as promising candidates for cancer treatment. However, challenges are posed by the limited number of suitable payload types, uncontrollable drug leakage, and lack of chemical groups for postmodification. To overcome those challenges, we developed a core-shell nanocomposite composed of zeolitic imidazolate framework-90 (ZIF-90) coated with spermine-modified acetalated dextran (SAD) by a facile microfluidics-based nanoprecipitation method. This nanocomposite could serve as a multidrug storage reservoir for the loading of two drugs with distinct properties, where the hydrophilic doxorubicin (DOX) was coordinately attached to the ZIF-90 framework, and hydrophobic photosensitizer IR780 was loaded into the SAD shell, enabling the combination therapy of photodynamic treatment with chemotherapy. Meanwhile, equipping ZIF-90 with a SAD shell not only substantially improved the pH-responsive drug release of ZIF-90 but also enabled the postformation conjugation of ZIF-90 with hyaluronic acid for specific CD44 recognition, thereby facilitating precise drug delivery to CD44-overexpressed tumor. Such a simple microfluidics-based strategy can efficiently overcome the limitations of solely MOF-based DDSs and greatly extend the flexibility of MOF biomedical applications.

Influence of Oxygen Pressure on the Domain Dynamics and Local Electrical Properties of BiFe0.95Mn0.05O3 Thin Films Studied by Piezoresponse Force Microscopy and Conductive Atomic Force Microscopy.

In this work, we have studied the microstructures, nanodomains, polarization preservation behaviors, and electrical properties of BiFe0.95Mn0.05O3 (BFMO) multiferroic thin films, which have been epitaxially created on the substrates of SrRuO3, SrTiO3, and TiN-buffered (001)-oriented Si at different oxygen pressures via piezoresponse force microscopy and conductive atomic force microscopy. We found that the pure phase state, inhomogeneous piezoresponse force microscopy (PFM) response, low leakage current with unidirectional diode-like properties, and orientation-dependent polarization reversal properties were found in BFMO thin films deposited at low oxygen pressure. Meanwhile, these films under high oxygen pressures resulted in impurities in the secondary phase in BFMO films, which caused a greater leakage that hindered the polarization preservation capability. Thus, this shows the important impact of the oxygen pressure on modulating the physical effects of BFMO films.

Prevalence of Cryptosporidium spp. in pigs in Shanghai, China.

A survey on prevalence of Cryptosporidium spp. in pigs at 12 farms in 8 suburban districts and 1 county of Shanghai was conducted under Sheather's sucrose flotation protocol and modified acid-fast stain methods from 2006 to 2009. A total of 2323 faecal samples were collected and Cryptosporidium spp. oocysts were detected in 800 samples (34.4%). Cryptosporidium was found in all 12 pig farms. Significant variations of prevalence were observed in different farms ranging from 14.1% to 90.6%. A follow-up survey on a positive pig farm for 13 consecutive months revealed that the most serious infection of Cryptosporidium spp. in pigs happened in winter and spring, and the lowest infection season was summer. Cryptosporidium spp. infection was mainly found in piglets within 2 months and no infection was found among those pigs of 90-180 days of age. The genotype analyses were carried out through PCR-RFLP and partial sequences analysis of small subunit ribosomal RNA (SSU rRNA) in some of the positive samples. Cryptosporidium suis (57/69, 82.6%), Cryptosporidium pig genotype II (6/69, 8.7%) and mixed infection of above two species/genotype (6/69, 8.7%) were found to be the main species/genotype in pigs in Shanghai area.

[Analysis on the association between job stress factors and depression symptoms].

OBJECTIVE: To identify the prevalence of depression symptoms among employees in Shanghai and to explore the association of job stress factors with depression symptoms. METHODS: Seven kinds of occupations were selected as subjects by convenient cluster sampling. Job stresses were assessed by core job stress scale and depression symptoms were measured by epidemiological survey depression scale (CES-D). Logistic regression and hierarchical moderated multiple regression were used for analysis. RESULTS: There were 1301 participants completing the questionnaires. The CES-D score reached 16. 83 +/- 8.63 and depression symptoms were in 46.2% of participants. The CSE-D score and the rate of depression symptoms were varied in different age, education and occupational status. Personal hobbies were helpful to reduce depression symptoms (OR = 0.63, 95% CI = 0.48-0.82). High social supports and high rewards were protect factors for depression symptoms, and the ORs were 0.38 (95% CI= 0.25-0.55) and 0.35 (95% CI = 0.21-0.58) respectively. High over-commitment and effort-reward imbalance were risk factors for depression symptoms, and the ORs were 2.72 (95% CI = 1.76-4.21) and 2.77 (95% CI = 1.09-7.05) respectively. The effort-reward imbalance model is more powerful in predicting depression symptoms than the job demand-control model. CONCLUSION: Effort-reward imbalance and high over-commitment are the risk factors for depression symptoms, more social supports and having hobbies are the protect factors for depression symptoms.

[Hierarchical regression analysis for relationship between job stress and job burnout in Shanghai employees].

OBJECTIVE: To identify related factors of job burnout in Shanghai employees. METHODS: Four hundred fifty-six employees in Shanghai were investigated in this study. Self-administered questionnaires were used to assess job burnout and job stress, based on Maslach Burnout Inventory and the Job Demand-Control model as well as Effort-Reward Imbalance Model. Hierarchical linear regression was employed to analyze the relationship of job burnout to personal characteristics and job stress. RESULTS: The indexes of three dimensions of job burnout were emotional exhaustion 19.70 +/- 8.92, depersonalization 11.95 +/- 4.45 and reduced personal accomplishment 28.10 +/- 10.08. Job stress was found to be affected differently in three dimensions of job burnout. Job demand, effort and over-commitment had positive impact on emotional exhaustion. Job control had a negative association with emotional exhaustion. There were significant relationship between depersonalization and age, sex and education of employees. Job control, reward and over-commitment affected the index of depersonalization. Education level and social support increased personal accomplishment index. CONCLUSION: It is necessary to reduce job stress and care about personal characteristics in preventing job burnout.

[Reliability and validity of Burnout Questionnaire in occupational population].

OBJECTIVE: To evaluate the reliability and validity of simple Burnout Questionnaire in occupational population. METHODS: A self-administered Burnout Questionnaire comprising 19 items was developed in light of Maslash Burnout Questionnaire and used for investigating 458 employees. RESULTS: Cronbach's alpha between total items of Burnout Questionnaire and each factor fell in between 0.82 and 0.85 through the consistency test. All 19 items of Burnout Questionnaire were subjected to factor analysis, and three latent factors were identified, wherein 56.3% of total variance could be explained. According to the contents described in the items and Maslash burnout theory, they were emotional exhaustion, depersonalization, and personal accomplishment. According to the covariance and the variance analysis, there was significant difference in the integral of the type of work among the three subitems (P < 0.01); there was significant difference in the integral of depersonalization between two sexes (P < 0.01); There were significant difference in the integral of the personal achievement among different level of education (P < 0.01). CONCLUSION: The reliability and validity of Burnout Questionnaire is acceptable and can be used for assessing burnout in occupational population.