Multifunctional Biomimetic Liposomes with Improved Tumor-Targeting for TNBC Treatment by Combination of Chemotherapy, Anti-Angiogenesis and Immunotherapy.

Triple negative breast cancer (TNBC) featuring high relapses and metastasis showed limited clinical therapeutic efficiency with chemotherapy for the extremely complex tumor microenvironment (TME), especially angiogenesis and immunosuppression. Combination of anti-angiogenesis and immunotherapy holds promise for effective inhibition of tumor proliferation and invasion, while it remains challenging for specific targeting drug delivery to tumors and metastatic lesions. Here, a multifunctional biomimetic liposome loading Gambogic acid (G/R-MLP) was developed using Ginsenoside Rg3 (Rg3) to substitute cholesterol and cancer cell membrane coating, which was designed to increase long-circulating action by a low immunogenicity and specifically deliver Gambogic acid (GA) to tumor site and metastatic lesions by homologous targeting and glucose transporter (GLUT) targeting. After G/R-MLP accumulated in the primary tumors and metastatic nodules, it synergistically enhanced the anti-tumor efficacy of GA, effectively suppressing the tumor growth and lung metastasis by killing tumor cells, inhibiting tumor cell migration and invasion, achieving anti-angiogenesis and improving the anti-tumor immunity. All in all, the strategy combining chemotherapy, anti-angiogenesis and immunotherapy improved therapeutic efficiency and prolonged survival, providing a new perspective for the clinical treatment of TNBC. This article is protected by copyright. All rights reserved.

Self-Assembled Nanoparticles from Xie-Bai-San Decoction: Isolation, Characterization and Enhancing Oral Bioavailability.

Background: Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD. Methods: N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds. Results: The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of -5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the Cmax, AUC0-∞, AUC0-t, T1/2 and MRT0-∞ values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats. Conclusion: The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects.

Unraveling the characteristics of dissolved organic matter removed by aluminum species based on FT-ICR MS analysis.

Given the complexity of dissolved organic matter (DOM) and its interactions with coagulant chemicals, the mechanisms of DOM removal by aluminum (Al) coagulants remains a significant unknown. In this study, six test waters containing DOM with molecular weight (MW, <1 kDa, 1-10 kDa and >10 kDa) and hydrophobicity (hydrophilic, transphilic and hydrophobic) were prepared and coagulated with Al0, Al13 and Al30. The molecular-level characteristics of DOM molecules that were removed or resistant to removal by Al species were analyzed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed that at the molecular level, saturated and reduced tannins and lignin-like compounds containing abundant carboxyl groups exhibited higher coagulation efficiency. Unsaturated and oxidized lipids, protein-like, and carbohydrates compounds were relatively resistant to Al coagulation due to their higher polarity and lower content of carboxyl groups. Al13 removed molecules across a wider range of molecular weights than Al0 and Al30, thus the DOC removal efficiency of Al13 was the highest. This study furthers the understanding of interactions between Al species and DOM, and provides scientific insights on the operation of water treatment plants to improve control of DOM.

Transformation of Al Species on Carbon Surfaces: Effects of Al Species and Carbon Surface Oxygen Groups.

Control of residual Al is critical, owing to its high tendency to accumulate in drinking water distribution systems and its potential risks to human health. Herein, the effects of surface properties of activated carbon (AC) on intercepting different Al species (including monomeric Al and polymeric Al species-Al13) are evaluated. The results showed that Al in the form of monomers was considerably adsorbed by AC; whereas Al in the form of polymeric Al13 was held to a much lower degree by AC, and the effluent Al concentration was even higher than that without AC. By comparing virgin AC and hydrogen thermal treated AC, the surface oxygen functional groups on the AC were proposed to play a critical role in the transformation of Al species. The oxygen functional groups on the AC surface can directly form complexes with monomeric Al, thereby inducing the binding of monomeric Al on the AC surface. However, the AC surface oxygen groups could not bind to polymeric Al13, and the interaction between AC surface oxygen groups and polymeric Al13 partially transforms Al13 into monomeric Al species, which inhibited the self-aggregation of Al13. This study aims to provide new insights into the control of residual Al in water treatment plants to ensure drinking water safety.

CD44-Targeted Photoactivatable Polymeric Nanosystem with On-Demand Drug Release as a "Photoactivatable Bomb" for Combined Photodynamic Therapy-Chemotherapy of Cancer.

Nowadays, the combined use of chemotherapy and photodynamic therapy (PDT) remains the most popular strategy for cancer treatment with high theraprutic efficacy. However, targeted therapy with the on-demand release of drugs is what most clinical treatments lack, leading to heavy side effects. Herein, a new CD44-targeted and red-light-activatable nanosystem, Ru-HA@DOX nanoparticles (NPs), was developed by conjugating hydrophilic biodegradable hyaluronic acid (HA) and hydrophobic photoresponsive ruthenium (Ru) complexes, which could encapsulate the chemotherapeutic drug doxrubicin (DOX). Ru-HA@DOX NPs can selectively accumulate at the tumor through the enhanced permeability and retention (EPR) effect and CD44-mediated endocytosis, thus avoiding off-target toxicity during circulation. After 660 nm of irradiation at the tumor site, Ru-HA@DOX NPs, as a "photoactivatable bomb", was split via the photocleavable Ru-N coordination bond to fast release DOX and produce singlet oxygen (1O2) for PDT. In general, Ru-HA@DOX NPs retained its integrity before irradiation and possessed minimal cytotoxicity, while under red-light irradiation, Ru-HA@DOX NPs showed significant cytotoxicity due to the release of DOX and production of 1O2 at the tumor. Chemotherapy-PDT of Ru-HA@DOX NPs resulted in a significant inhibition of tumor growth in A549-tumor-bearing mice and reduced the cardiotoxicity of DOX. Therefore, this study offers a novel CD44-targeted drug-delivery system with on-demand drug release for synergistic chemotherapy-PDT.

Suppression of performance of activated carbon filter due to residual aluminum accumulation.

Extending the lifetime of granular activated carbon (GAC) filters with no significant loss in their effectiveness is a considerable challenge for drinking water supply utilities. However, the effects of residual Al from coagulants on GAC performance are rarely considered. Herein, in-service GAC samples obtained from full-scale water treatment plants were investigated to evaluate the amount of accumulated Al. Although the Al concentration in water was two to three times lower than the Ca concentration, Al exhibited considerable accumulation (second to Ca accumulation) in in-service GAC samples (0.68-8.63 mg g-1). Surface characterization results indicated that Al accumulation could have been caused by the co-precipitation of Al with Ca and Si to form Ca4Al2Si3O10·H2O and Ca4Al6O12SO4, self-precipitation or complexion with -OH/-COOH on the GAC or biofilm surfaces. Correlation analysis of the accumulated Al and GAC properties implied that Al accumulation considerably reduced the surface area of GAC by ∼30%. Lab simulation experiments indicated that the removal of dissolved organic matter was reduced by 6-10% when additional Al was loaded. In addition, results showed that the residual Al (up to 200 µg L-1) considerably affected the extracellular polymeric substance component and microorganism community structure. In summary, strict control of residual Al is beneficial for maintaining the efficacies of GAC and biologically activated carbon.

Novel insights into indoor air purification capability of microalgae: characterization using multiple air quality parameters and comparison with common methods.

Indoor air purification received more attention recently. In this study, the effects of six common indoor ornamental plants (Epripremnum aureum, Chlorphytum comosum, Aloe vera, Sedum sediforme, Cereus cv. Fairy Castle, and Sedum adolphii) and three kinds of microalgae (Chlorella sp. HQ, Scenedesmus sp. LX1, and C. vulgaris) on the removal of four types of air pollutants (particulate matters less than 2.5 (PM2.5) and 10 µm (PM10) in size, formaldehyde (HCHO) and total volatile organic compounds (VOCS)) in test chamber compared with common physical purification methods (high efficiency particulate air filter and nano activated carbon absorption) were investigated. Their effects on oxygen, carbon dioxide, and relative humidity were also evaluated. The results showed that microalgae, especially C. vulgaris, was more suitable for removing PM2.5 and PM10, and the removal rates were 55.42 ± 25.77% and 45.76 ± 5.32%, respectively. The removal rates of HCHO and VOCs by all three kings of microalgae could reach 100%. Part of ornamental plants took a longer time to achieve 100% removal of HCHO and VOCs. Physical methods were weaker than ornamental plants and microalgae in terms of increased relative humidity and O2 content. In general, microalgae, especially C. vulgaris could purify indoor air pollutants more efficiently. The above studies provided data and theoretical support for the purification of indoor air pollutants by microalgae.

Predictors of spinal trauma care and outcomes in a resource-constrained environment: a decision tree analysis of spinal trauma surgery and outcomes in Tanzania.

OBJECTIVE: The burden of spinal trauma in low- and middle-income countries (LMICs) is immense, and its management is made complex in such resource-restricted settings. Algorithmic evidence-based management is cost-prohibitive, especially with respect to spinal implants, while perioperative care is work-intensive, making overall care dependent on multiple constraints. The objective of this study was to identify determinants of decision-making for surgical intervention, improvement in function, and in-hospital mortality among patients experiencing acute spinal trauma in resource-constrained settings. METHODS: This study was a retrospective analysis of prospectively collected data in a cohort of patients with spinal trauma admitted to a tertiary referral hospital center in Dar es Salam, Tanzania. Data on demographic, clinical, and treatment characteristics were collected as part of a quality improvement neurotrauma registry. Outcome measures were surgical intervention, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade improvement, and in-hospital mortality, based on existing treatment protocols. Univariate analyses of demographic and clinical characteristics were performed for each outcome of interest. Using the variables associated with each outcome, a machine learning algorithm-based regression nonparametric decision tree model utilizing a bootstrapping method was created and the accuracy of the three models was estimated. RESULTS: Two hundred eighty-four consecutively admitted patients with acute spinal trauma were included over a period of 33 months. The median age was 34 (IQR 26-43) years, 83.8% were male, and 50.7% had experienced injury in a motor vehicle accident. The median time to hospital admission after injury was 2 (IQR 1-6) days; surgery was performed after a further median delay of 22 (IQR 13-39) days. Cervical spine injury comprised 38.4% of the injuries. Admission AIS grades were A in 48.9%, B in 16.2%, C in 8.5%, D in 9.5%, and E in 16.6%. Nearly half (45.1%) of the patients underwent surgery, 12% had at least one functional improvement in AIS grade, and 11.6% died in the hospital. Determinants of surgical intervention were age ≤ 30 years, spinal injury level, admission AIS grade, delay in arrival to the referral hospital, undergoing MRI, and type of insurance; admission AIS grade, delay to arrival to the hospital, and injury level for functional improvement; and delay to arrival, injury level, delay to surgery, and admission AIS grade for in-hospital mortality. The best accuracies for the decision tree models were 0.62, 0.34, and 0.93 for surgery, AIS grade improvement, and in-hospital mortality, respectively. CONCLUSIONS: Operative intervention and functional improvement after acute spinal trauma in this tertiary referral hospital in an LMIC environment were low and inconsistent, which suggests that nonclinical factors exist within complex resource-driven decision-making frameworks. These nonclinical factors are highlighted by the authors' results showing clinical outcomes and in-hospital mortality were determined by natural history, as evidenced by the highest accuracy of the model predicting in-hospital mortality.

Rapid analysis of differential chemical compositions of Poria cocos using thin-layer chromatography spray ionization-mass spectrometry.

Poria cocos, with medicinal and edible properties, contains multiple chemical components that pose difficulties in its quality control. Herein, we established a simple thin-layer chromatography spray ionization-mass spectrometry (TLCSI-MS) device that allows the simultaneous separation and identification of bioactive compounds. The triterpene acids in different medicinal parts of Poria cocos were characterized, and the markers of differences were revealed. The quantitative analysis of its pharmaceutical preparation has also been performed to verify the feasibility. The study provides a new analytical perspective for the screening and identification of multiple compounds and a good option for the quality evaluation of herbal medicines and foods.

Field study on the transportation characteristics of PFASs from water source to tap water.

Perfluoroalkyl substances (PFASs) can occur in water sources, pass through drinking water treatment plants (DWTPs), drinking water distribution systems (DWDSs), to the consumer taps. This investigation was carried out to present the transportation behaviors of 17 PFASs, involving seven DWTPs with different water sources, raw water transportation modes, treatment processes, and DWDS structures in eastern and northern China. The results showed that the long-distance raw water transportation pipelines removed a certain extent of PFASs from raw water, probably due to the accumulation of loose deposits. The long-distance, open-channel South-to-North water diversion increased PFAS contamination risk. In the DWTPs, granular activated carbon (GAC) adsorption and ultraviolet radiation removed less than 25% of PFASs, but ozonation-biological activated carbon (O3-BAC) was superior to GAC alone in removing PFASs. Loose deposits couldsignificantly influence PFAS accumulation and release within branch-structured DWDSs. In loop-structured DWDSs, finished water with different PFAS characteristics could mix along the pipeline, with the corresponding DWTP as the center, ultimately forming a relatively uniform distribution in the entire DWDS.

Field studies of aluminum release and deposition in drinking water distribution systems.

Aluminum (Al) release and deposition in drinking water distribution systems (DWDS) are highly detrimental to tap water quality. In this study, five drinking water treatment plant supply areas in two cities of China were examined to understand the transportation stability of Al in the DWDS. The two cities were selected based on the wide disparity reported in pH and turbidity in the finished and tap water qualities, with higher fluctuation of pH (average 8.0) and turbidity (average 0.78 NTU) reported in the northern and southern cities, respectively. Results showed that hydraulic conditions such as hydraulic shock or increased flow velocity had a more significant effect on the release and deposition of particulate Al, which could be reflected by turbidity when it was greater than 0.3 NTU, since turbidity and particulate Al were significantly positively correlated. Particulate Al concentration varied by more than 140 µg/L when turbidity fluctuated within 0.45-1.67 NTU. However, when turbidity was below 0.3 NTU, the particulate Al transported stably at low concentration. pH fluctuations contributed to the change of soluble Al concentration. Even above 50 µg/L soluble Al in the finished water could transport stably in the DWDS when pH fluctuated slightly in 6.6-7.0. However, when the pH fluctuated in 7.8-8.4, the soluble Al concentration varied by more than 100 µg/L. This study provides reference indicators of turbidity and pH for identifying the risk of Al in the DWDS.

Continuous Electroencephalographic Monitoring in the Intensive Care Unit: A Cross-Sectional Study.

OBJECTIVE: Research on continuous electro-encephalographic monitoring (cEEG) in the intensive care unit (ICU) has previously focused on neuroscience ICUs. This study determines cEEG utilization within a sample of specialty ICUs world-wide. METHODS: A cross-sectional electronic survey of attending level physicians across various intensive care settings. Twenty-five questions developed from consensus statements on the use of cEEG in the critically ill sent as an electronic survey. RESULTS: Of all, 9344 were queried and 417 (4.5%) responses were analyzed with 309 (74%) from the United States and 74 (18%) internationally. Intensive care units were: medical (10%), surgical (6%), neurologic/neurosurgical (12%), cardiac (4%), trauma (3%), pediatrics (29%), burn (<1%), multidisciplinary (30%), and other (5%). Intensive care units were: academic (65%), community (18%), public (3%), military (1%), and other (13%). Specialized cEEG teams were available in 71% of ICUs. Rapid 24/7 access and cEEG interpretation was available in 32% of ICUs. Interpretation changed clinical management frequently (28%) and sometimes (45%). CONCLUSIONS: Despite guideline recommendations for cEEG use, there is a discordance between availability, night coverage, and immediate interpretation. Only 27% have institutional protocols for indications and duration of cEEG monitoring. Furthermore, cEEG may be underutilized in nonneurologic ICUs as well as ICUs in smaller nonacademic affiliated hospitals and those outside of the United States.

Growth and high-valued products accumulation characteristics of microalgae in saline-alkali leachate from Inner Mongolia.

In this study, the growth and high-valued products accumulation characteristics of three common high-valued microalgae (Chlorella sp. HQ, Scenedesmus sp. LX1, and Chlorella vulgaris) in saline-alkali leachate were compared to select the species with greatest utilization potential. The results showed that after 28 days of cultivation, among three microalgae, Chlorella sp. HQ grew best with its maximum density at peak of 1.16 × 107 cells mL-1 and lipid production per unit cell (0.047 ± 0.006 × 10-7 mg cell-1) and lipid content (18.18 ± 3.14%) were largest. The triacylglycerol (TAG) yield and content of Scenedesmus sp. LX1 were the highest, reaching 0.005 ± 0.000 × 10-7 mg cell-1 and 19.74 ± 2.53%, respectively, which was slightly higher than those of Chlorella sp. HQ. According to comprehensive comparison, Chlorella sp. HQ was most suitable to grow in the saline-alkali leachate in terms of algal density, lipid yield, and content. The potential comparison and effects of salinity on the high-valued products accumulation of Chlorella sp. HQ compared with those in SE standard medium, reclaimed water, and tap water were further carried out. It was found that the density order of Chlorella was saline-alkali leachate > SE medium > reclaimed water > tap water. And the Chlorella density in the leachate with a salinity of 0.14% was greater than the other three salinities (0.32%, 0.45%, and 0.6%) at the end of cultivation. While the maximum lipid yield per unit cell and lipid content of Chlorella occurred in the salinity of 0.6%, which indicated that high salinity promoted the accumulation of lipid. Furthermore, other high-valued products (including starch, protein, total sugar, and photosynthetic pigments) accumulation characteristics were analyzed and found that they were all superior than those in SE medium. And with the salinity decreased, the microalgal protein and starch contents decreased. The contents of photosynthetic pigment and total sugar reached a maximum at salinities of 0.32% and 0.45%, respectively.

Influences of carbon and nitrogen sources and metal ions on the heterotrophic culture of Scenedesmus sp. LX1.

In this study, the influences of organic carbon sources (OCS, including xylose, glucose, maltose, sucrose, and starch) and inorganic and organic nitrogen sources (INS, including ammonia chloride and sodium nitrate; ONS, including arginine, alanine, proline, and valine) and metal ions (including Na+, K+, Mn2+, Zn2+ and Cu2+) on the growth, lipid accumulation, and nitrogen and phosphorus (N&P) removal capabilities of oleaginous Scenedesmus sp. LX1 under heterotrophic conditions were investigated. The results showed that glucose was the only OCS for Scenedesmus sp. LX1 to grow well with specific growth rate of 0.935 days-1, maximum biomass of 1.72 g L-1, and largest removal rates of N&P and organic carbon reaching 72.228%, 93.034%, and 19.208%, respectively. After 11 days of cultivation, the maximal biomass reached in the group with starch or glucose while maximal lipid and triacylglycerol (TAG) yields reached in the groups with maltose and sucrose, respectively. Sodium nitrate was best nitrogen source as the largest algal density, maximal yields of lipids and TAGs, and highest N&P removal rates reached up to 1.105 × 107 cells·mL-1, 196.70 mg L-1, 5.19 mg L-1, 89.61% and 100%, respectively. Scenedesmus sp. LX1 was found to have great tolerance to Na+, K+, Mn2+, and Zn2+ while 0.5 mg L-1 Cu2+ had a strong inhibition on growth and N&P removal rate of Scenedesmus sp. LX1. Concentration increasing of five metal ions all caused the yield increases of microalgal lipid and TAGs. Graphical abstract.