Glutathione Consumptive Dual-Sensitive Lipid-Composite Nanoparticles Induce Immunogenic Cell Death for Enhanced Breast Tumor Therapy.

Although chemotherapy remains the standard therapy for tumor treatment, serious side effects can occur because of nontargeted distribution and damage to healthy tissues. Hollow mesoporous silica nanoparticles (HMSNs) modified with lipids offer potential as delivery systems to improve therapeutic outcomes and reduce adverse effects. Herein, we synthesized HMSNs with integrated disulfide bonds (HMSN) for loading with the chemotherapeutic agent oxaliplatin (OXP) which were then covered with the synthesized hypoxia-sensitive lipid (Lip) on the surface to prepare the dual-sensitive lipid-composite nanoparticles (HMSN-OXP-Lip). The empty lipid-composite nanoparticles (HMSN-Lip) would consume glutathione (GSH) in cells because of the reduction of disulfide bonds in HMSN and would also inhibit GSH production because of NADPH depletion driven by Lip cleavage. These actions contribute to increased levels of ROS that induce the immunogenic cell death (ICD) effect. Simultaneously, HMSN-Lip would disintegrate in the presence of high concentrations of GSH. The lipid in HMSN-OXP-Lip could evade payload leakage during blood circulation and accelerate the release of the OXP in the tumor region in the hypoxic microenvironment, which could significantly induce the ICD effect to activate an immune response for an enhanced therapeutic effect. The tumor inhibitory rate of HMSN-OXP-Lip was almost twice that of free OXP, and no apparent side effects were observed. This design provides a dual-sensitive and efficient strategy for tumor therapy by using lipid-composite nanoparticles that can undergo sensitive drug release and biodegradation.

Nano-Drug Delivery Systems Based on Different Targeting Mechanisms in the Targeted Therapy of Colorectal Cancer.

Colorectal cancer (CRC) is a usual digestive tract malignancy and the third main cause of cancer death around the world, with a high occurrence rate and mortality rate. Conventional therapies for CRC have certain side effects and restrictions. However, the exciting thing is that with the rapid development of nanotechnology, nanoparticles have gradually become more valuable drug delivery systems than traditional therapies because of their capacity to control drug release and target CRC. This also promotes the application of nano-drug targeted delivery systems in the therapy of CRC. Moreover, to make nanoparticles have a better colon targeting effect, many approaches have been used, including nanoparticles targeting CRC and in response to environmental signals. In this review, we focus on various targeting mechanisms of CRC-targeted nanoparticles and their latest research progress in the last three years, hoping to give researchers some inspiration on the design of CRC-targeted nanoparticles.

Effect of enrichment conditions of secondary feeding on the synthesis of polyhydroxyalkanoates (PHAs) by activated sludge.

Polyhydroxyalkanoates (PHAs) are biodegradable plastics with great performance and development prospects. However, their traditional anaerobic/aerobic enrichment process requires a high concentration of dissolved oxygen (DO), resulting in high energy consumption. In this study, an anaerobic/oxygen-limited with secondary feeding enrichment mode was used to enhance the synthesis of PHAs while reducing energy consumption. The enrichment process of PHAs-synthesizing bacteria lasted up to 100 days, and the experiment was conducted to investigate the change of the PHAs synthesizing ability of the system in this mode by detecting the PHAs content and community distribution of the activated sludge under different stages. Under these conditions, the system enriched two major genera of PHAs-synthesizing bacteria, Thauera (30.21%) and Thiothrix (21.30%). The content of PHAs in the sludge increased from 4.51% to 30.87% and was able to achieve a concomitant increase in poly(3-hydroxyvalerate) (PHV) monomer content. After nitrogen limitation (C/N = 150) treatment, the content of PHAs reached 63.05%. The results showed that the enrichment mode of anaerobic/oxygen-limited with secondary feeding could enrich more PHAs-synthesizing bacteria and significantly increase the synthesis amount of PHAs, which revealed the great potential of this mode in solid waste value-added and reduce the production cost of PHAs and could provide a theoretical basis for the production of PHAs from activated sludge.

Achievements and Bottlenecks of PEGylation in Nano-delivery Systems.

Poly(ethylene glycol) (PEG) has been widely applied in the biomedical field as a gold standard. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles, also known as PEGylation, is a common method to improve the efficiency of drug delivery and pharmacokinetics in vivo. The effect of PEGylation on the in vivo fate of various formulations has been and continues to be extensively studied based on the successful PEGylation of proteins to improve in vivo circulation time and reduce immunogenicity. The PEG shell protects the particles from aggregation, immune recognition, and phagocytosis, thereby prolonging the in vivo circulation time. This article mainly describes the development background, advantages and applications of PEGylation in the field of drug delivery, its defects or development bottlenecks, and possible alternatives.

Do social media campaigns foster vaccination adherence? A systematic review of prior intervention-based campaigns on social media.

The COVID-19 pandemic has demonstrated the importance of large-scale campaigns to facilitate vaccination adherence. Social media presents unique opportunities to reach broader audiences and reduces the costs of conducting national or global campaigns aimed at achieving herd immunity. Nonetheless, few studies have reviewed the effectiveness of prior social media campaigns for vaccination adherence, and several prior studies have shown that social media campaigns do not increase uptake rates. Hence, our objective is to conduct a systematic review to examine the effectiveness of social media campaigns and to identify the reasons for the mixed results of prior studies. Our methodology began with a search of seven databases, which resulted in the identification of 92 interventions conducted over digital media. Out of these 92 studies, only 15 adopted social media campaigns for immunization. We analyzed these 15 studies, along with a coding scheme we developed based on reviews of both health interventions and social media campaigns. Multiple coders, who were knowledgeable about social media campaigns and healthcare, analyzed the 15 cases and obtained an acceptable level of inter-coder reliability (> .80). The results from our systematic review show that only a few social media campaigns have succeeded in enhancing vaccination adherence. In addition, few campaigns have utilized known critical success factors of social media to induce vaccination adherence. Based on these findings, we discuss a set of research questions that informatics scholars should consider when identifying opportunities for using social media to resolve one of the most resilient challenges in public health. Finally, we conclude by discussing how the insights drawn from our systematic reviews contribute to advancing theories, such as social influence and the health belief model, into the realm of social media-based health interventions.

Chemical digestion method to promote activated sludge cell wall breaking and optimize the polyhydroxyalkanoate (PHA) extraction process.

A novel protocol for the recovery of PHA from mixed-cultures proposed. In this experiment, activated sludge for PHA synthesis was investigated and a two-stage chemical digestion method was used for activated sludge to improve the yield of PHA. The highest PHA extraction combination that could be obtained in this experiment was sodium hypochlorite(NaClO) plus sodium dodecyl sulfate (SDS), and the optimal concentration of NaClO solution was 25 % (v/v), and the ratio of the dry weight of activated sludge to SDS was 1:2. The recovery and purity of PHA were 72.14 % and 54.47 %, respectively. The reaction time between NaClO and activated sludge affects the recovery of PHA, and the optimal reaction time of NaClO was experimentally obtained as 30 min. The purity of the PHA extract obtained after purification using methanol was improved.

"Targeted plus controlled" - Composite nano delivery system opens the tumor vascular and microenvironment normalization window for anti-tumor therapy.

The bottleneck of traditional anti-tumor therapy is mainly limited by the abnormal microenvironment of tumors. Leaky vessels are difficult for drugs or immune cells to penetrate deep into tumors, but tumor cells can easily escape through which and metastasize to other organs. Reprogramming the tumor microenvironment is one of the main directions for anti-cancer research, among which, tumor vascular normalization has received increasing attention. However, how to control the dose and time of anti-angiogenic drugs for stable vascular normalizing effect limits it for further research. We developed a composite nano delivery system, P-V@MG, with double delivery function of pH-responsibility and sustained drug release. The PHMEMA shell improves amphiphilicity of nano delivery system and prolongs in vivo retention, and releases V@MG in the weakly acidic tumor microenvironment, which slowly release anti-angiogenic drugs, Vandetanib. We found that P-V@MG not only prolonged the normalization window of tumor vascular but also reprogram tumor microenvironment with increased perfusion, immune cells infiltration and relieved hypoxia, which further opened the pathway for other anti-cancer therapeutics. This synergy was proved by the improving anti-tumor efficiency by combination of P-V@MG with the doxorubicin hydrochloride in 4 T1 breast cancer model suggesting the desirable value of pro-vascular normalization nano delivery systems in the field of anti-tumor combination therapy.

Optimization of activated sludge polyhydroxyalkanoates(PHAs) synthesis system by performing sludge activity recovery experiments and varying the initial sludge concentration.

Polyhydroxyalkanoates(PHAs) are considered a good alternative to petroleum-based plastics because of their good biodegradability and biocompatibility. The synthesis of PHAs using activated sludge can not only solve the problem of the high cost of pure cultures but also improve the utilization value of activated sludge. In this study, sludge activity recovery experiments were firstly conducted and the effects of different initial sludge concentrations on the activated sludge PHAs synthesis system were further investigated. the initial sludge concentrations were 1#SBR (2800 ± 50) mg/L, 2#SBR (4200 ± 50) mg/L, and 3#SBR (5500 ± 50) mg/L. The results showed that the activity, sedimentation performance and PHAs synthesis capacity of activated sludge were enhanced after the sludge activity recovery experiment. At the initial sludge concentration of 4200 mg/L, the activated sludge PHAs synthesis system was operated stably and the synthesis efficiency of PHAs was enhanced. In contrast, at the initial sludge concentration of 2800 and 5500 mg/L, the steady state of the activated sludge PHAs synthesis system was damaged to different degrees at different times, and the synthesis efficiency of PHAs was greatly reduced.

Anti-angiogenic nano-delivery system promotes tumor vascular normalizing and micro-environment reprogramming in solid tumor.

Aberrant tumor vasculature leads to the malignant tumor microenvironment (TME) for tumor progression. Research has found temporary tumor vascular normalization after treated with low-dose anti-angiogenic agents, however, has paid little attention to prolonging the normalization window and its further influence on tumor tissue. Based on the dose- and time-dependent effect of anti-angiogenic agents, we developed V@LDL NPs, a nano-delivery system sustainedly releasing Vandetanib, an anti-VEGFR2 inhibitor, to control the dose of drug to the normalizing level, and prove its stable tumor vascular normalizing effect in 4 T1 breast cancer model. Furthermore, long-term normalized vasculature could improve tumor perfusion, then provide a circulation to reverse abnormalities in TME, such as hypoxia and heterogeneity, and also inhibit tumor progression. Our findings demonstrate that stable tumor vascular normalization could be a considerable strategy for long-term change to remodel TME and probably result in a therapeutic benefit to anti-cancer treatment, which could be achieved by anti-angiogenic nano-delivery system.

Sentiment on Dissemination about COVID-19 of Mainstream Media Around the World: What Information are They Delivering?

The purpose of this article is to research the sentiment and topic classification about COVID-19 of mainstream social media in the United States to interpret what information the American public receives toward the COVID-19, and what are the perspectives of News and articles on epidemics in different topic fields. The study will extract unigrams to trigrams of different articles to judge the sentiments of articles, and use region-related keywords, dates, and topics extracted by classification as independent variables to measure the differences between disparate features. The result shows that news related to the business and health fields are more frequent (48.2% and 20.8% respectively). It also reveals that news regarding entertainment and technologies has a lower rate to be negative during the pandemic (5.6% and 11.1% respectively). With time flows during the research period, the sports news has a trend to be more negative, and a trend to be more positive for entertainment news and technology news.

Chitosan derived glycolipid nanoparticles for magnetic resonance imaging guided photodynamic therapy of cancer.

Currently, the development of polysaccharide, especially chitosan (CS), based drug delivery system to afford magnetic resonance imaging (MRI) guided theranostic cancer therapy remains largely unexplored. Herein, we successfully developed a CS derived polymer (Gd-CS-OA) through chemical conjugation of CS, octadecanoic acid (OA) and gadopentetic acid (GA). After self-assemble into glycolipid nanoparticles to loaded chlorin e6 (Ce6), the resulted Gd-CS-OA/Ce6 was able to realize MRI guided photodynamic therapy (PDT) of cancer. Our results revealed that Gd-CS-OA was able to increase the MRI sensitivity as compared to Gd-DTPA with decent residence time and preferable excretion behavior in vivo. Moreover, the Gd-CS-OA/Ce6 showed negligible hemolysis, satisfactory ROS generation and stability in physiological environments with preferable cellular uptake and enhanced in vitro cytotoxicity (through elevated ROS generation) on 4T1 cells. Most importantly, Gd-CS-OA/Ce6 demonstrated promising in vivo tumor targetability (enhanced penetration and retention effect) and powerful MRI guided tumor ablation through PDT on in situ 4T1 tumor model.