Hybrid Cell Membrane-Based Nanoplatforms for Enhanced Immunotherapy against Cancer and Infectious Diseases.

Immunotherapy based on nanoplatforms is a promising approach to treat cancer and infectious diseases, and it has achieved considerable progress in clinical practices. Cell membrane-based nanoplatforms endow nanoparticles with versatile characteristics, such as half-life extension, targeting ability, and immune-system regulation. However, monotypic cell membrane usually fails to provoke strong immune response for immunotherapy while maintaining good biosafety. The integration of different cell-membrane types provides a promising approach to construct multifunctional nanoplatforms for improved immunotherapeutic efficacy by enhancing immunogenicity or targeting function, evading immune clearance, or combining with other therapeutic modalities. In this review, the design principles, preparation strategies, and applications of hybrid cell membrane-based nanoplatforms for cancer and infection immunotherapy are first discussed. Furthermore, the challenges and prospects for the potential clinical translation of hybrid cell membrane-based nanoplatforms are discussed.

Biofunctional lipid nanoparticles for precision treatment and prophylaxis of bacterial infections.

The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.

Metagenomic next-generation sequencing, instead of procalcitonin, could guide antibiotic usage in patients with febrile acute necrotizing pancreatitis: a multicenter, prospective cohort study.

BACKGROUNDS: The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. MATERIALS AND METHODS: The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. RESULTS: From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. CONCLUSION: Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

Toxic effects of combined exposure to cadmium and diclofenac on freshwater crayfish (Procambarus clarkii): Insights from antioxidant enzyme activity, histopathology, and gut microbiome.

In recent years, excessive discharge of pollutants has led to increasing concentrations of cadmium (Cd) and diclofenac (DCF) in water; however, the toxicity mechanism of combined exposure of the two pollutants to aquatic animals has not been fully studied. Procambarus clarkii is an economically important aquatic species that is easily affected by Cd and DCF. This study examined the effects of combined exposure to Cd and DCF on the tissue accumulation, physiology, biochemistry, and gut microflora of P. clarkii. The results showed that Cd and DCF accumulated in tissues in the order of hepatopancreas > gill > intestine > muscle. The hepatopancreas and intestines were subjected to severe oxidative stress, with significantly increased antioxidant enzyme activity. Pathological examination revealed lumen expansion and epithelial vacuolisation in the hepatopancreas and damage to the villous capillaries and wall in the intestine. The co-exposure to Cadmium (Cd) and Diclofenac (DCF) disrupts the Firmicutes/Bacteroidetes (F/B) ratio, impairing the regular functioning of intestinal microbiota in carbon (C) and nitrogen (N) cycling. This disturbance consequently hinders the absorption and utilization of energy and nutrients in Procambarus clarkii. This study offers critical insights into the toxicological mechanisms underlying the combined effects of Cd and DCF, and suggests potential approaches to alleviate their adverse impacts on aquatic ecosystems.

Changes of stressful life events, coping strategies and mental health among youths in the pre- and post-coronavirus 2019 pandemic era: A cross-sectional study.

BACKGROUND: In the pandemic era, stressful life events (StressLEv) aggravated the impact on mental health. However, youths exhibited different responses to StressLEv because of diverse coping strategies, social support, and emotional intelligence before and after the pandemic. AIMS: To explore the changes in StressLEv and coping strategies before and after the coronavirus 2019 pandemic, as well as report the associations among mental health and related factors in a sample of Chinese youths experiencing the post-pandemic era. METHOD: A cross-sectional study using convenience sampling was conducted from July 1 to August 30, 2022, covering 3,038 youths aged 14 to 25 in China. Multiple logistic regression was conducted for crude odds ratios (ORs) and adjusted ORs. The relationships between lasso-selected variables was examined using structural equation modeling. RESULTS: More StressLEv and limited coping strategies were reported after the pandemic. In the post-pandemic era, BSI-positive youths (youths diagnosed as considered case by Brief Symptom Inventory, BSI) reported more StressLEv (BSI-positive: mean = 75.47; BSI-negative: mean = 28.69), less social support (BSI-positive: mean = 31.81; BSI-negative: mean = 39.22), and lower emotional intelligence (BSI-positive: mean = 75.34; BSI-negative: mean = 89.42). The willingness to engage in mental health counseling (OR: no vs. yes: 1.89; uncertain vs. yes: 4.42), being punished (OR: 1.27), adaptation problems (OR: 1.06), task-oriented coping (OR: 0.95), social diversion coping (OR: 0.90), objective support (OR: 0.90), utilization of social support (OR: 0.81), and regulation of emotion in oneself (OR: 0.94) were associated with mental health. Structural equation modeling supported our theoretical framework. CONCLUSIONS: Pandemic-induced mental health problems should not be ignored. The proposed response mechanisms could guide the development of effective interventions, which can help youths better cope with StressLEv and maintain good mental health.

Neutrophil-inspired photothermo-responsive drug delivery system for targeted treatment of bacterial infection and endotoxins neutralization.

BACKGROUND: P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. METHODS: A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. RESULTS: Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. CONCLUSION: The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.

Fight bacteria with bacteria: Bacterial membrane vesicles as vaccines and delivery nanocarriers against bacterial infections.

Bacterial membrane vesicles (MVs) are particles secreted by bacteria with diameter of 20-400 nm. The pathogen-associated molecular patterns (PAMPs) present on the surface of MVs are capable of activating human immune system, leading to non-specific immune response and specific immune response. Due to the immunostimulatory properties and proteoliposome nanostructures, MVs have been increasingly explored as vaccines or delivery systems for the prevention and treatment of bacterial infections. Herein, the recent progresses of MVs for antibacterial applications are reviewed to provide an overview of MVs vaccines and MVs-related delivery systems. In addition, the safety issues of bacterial MVs are discussed to demonstrate their potential for clinical translation. In the end of this review, the challenges of bacterial MVs as vaccines and delivery systems for clinical applications are highlighted with the purpose of predicting future research directions in this field.

Biosorption of Pb(2+) by Saccharomyces cerevisiae in static and dynamic adsorption tests.

This paper demonstrates the Pb(2+) adsorption capacity and adsorption rate of Saccharomyces cerevisiae by both static and dynamic testing to verify its feasibility as a heavy metal bio-absorbent in wastewater treatment. The static testing was divided into two parts. First, we tested S. cerevisiae by itself, and then we tested immobilized S. cerevisiae. In static testing of the non-immobilized S. cerevisiae, the Pb(2+) adsorption capacity and adsorption rate increased up to 6.52 mg/g and 52.94%, respectively, with time. After immobilization, the Pb(2+) adsorption capacity and adsorption rate reached 10 mg/g and 80%, respectively. In dynamic testing, the optimal saturated adsorption capacity of immobilized S. cerevisiae for Pb(2+) was 6.64 mg/g. In addition to the static and dynamic testing of adsorption capacity and rate, we used SEM imaging to analyze the mechanics of adsorption, and the images showed that the cell wall played the major roll in Pb(2+) adsorption.

Evaluation of water quality in Er-longshan reservoir by fuzzy model.

The Er-longshan reservoir, located in Harbin city, Heilongjiang province, plays a significant role in development of economy and society. It's one of the most important fresh water sources for drinking as well as the safeguard of flood and soil erosion. Thus, as the monitored place in this study, its water quality was measured and predicted through a fuzzy model. The objective of this paper is to illustrate how to set up an appropriate subjection function model to solve the fuzzy problem. Most environmental monitoring data that can not be compared may be mapped into subjection degrees, and analyzed for their weight coefficients, yielding the best situation in multi-objective comprehensive exponential decision-making matrix.An appropriate subjection function model was set up to solve the fuzzy problem. Five kinds of pollution sources were investigated: the point source, the plane source, the entering river (Feiketu river), precipitation and falling dust and touring pollution around the reservoir area respectively. The distribution of floating algae in Er-longshan reservoir was also examined. Farmland plane source pollution was found to be the major controllable pollution source by monitoring TN and TP pollution loads, which occupy 84.8% and 84.0% of the controllable pollution source respectively. When we evaluate data of water quality, the concentration of part pollutant factors increases while others may decreases, then whether the whole water quality is to increase or decrease, from the monitor data is not easy to judge. In this study we used the fuzzy theory to analyze the trends of water quality fluctuations in the Er-longshan reservoir. COD(Mn), BOD, TN and TP were selected as main contamination factors. The results showed that the primary pollutants were nitrogen and phosphorus by calculating the weight coefficient e(i) of contamination factors from 1996 to 2005. According to fuzzy comprehensive exponent z(j) evaluating water quality of reservoir from 1996 to 2005, the ten-year water quality dynamic trend was studied.