Retention Effect Research Articles

Reprogramming monocytes into M2 macrophages as living drug depots to enhance treatment of myocardial ischemia-reperfusion injury

Delivering therapeutic agents efficiently to inflamed regions remains an intractable challenge following myocardial ischemia-reperfusion injury (MI/RI) due to the transient nature of the enhanced permeability and retention effect, which disappears after 24 h. Leveraging the inflammation-homing and plasticity properties of circulating monocytes (MN) as hitchhiking carriers and further inducing their polarization into anti-inflammatory phenotype macrophages upon reaching the inflamed sites is beneficial for MI/RI therapy. Herein, DSS/PB@BSP nanoparticles capable of clearing reactive oxygen species and inhibiting inflammation were developed by employing hollow Prussian blue nanoparticles (PB) as carriers to encapsulate betamethasone sodium phosphate (BSP) and further modified with dextran sulfate sodium (DSS), a targeting ligand for the scavenger receptor on MN. This formulation was internalized into MN as living cell drug depots, reprogramming them into anti-inflammation type macrophages to inhibit inflammation. In vitro assessments revealed the successful construction of the nanoparticle. In a murine MI/RI model, circulating MN laden with these nanoparticles significantly enhanced drug delivery and accumulation at the cardiac injury site, exhibiting favorable therapeutic ability and promoting M2-biased differentiation. Our study provides an effective approach with minimally invasion and biosecurity that makes this nanoplatform as a promising candidate for immunotherapy and clinical translation in the treatment of MI/RI.

Residue retention and precision nitrogen management effects on soil physicochemical properties and productivity of maize-wheat-mungbean system in Indo-Gangetic Plains

Maize-based crop systems are promoted in large scale in South Asia because they are more sustainable and efficient than rice-based systems. In the present study, using two combinations of crop residue management practices (CRM) with four precision nitrogen (N) management (PNM) systems, we assessed the impacts on soil physicochemical characteristics [soil organic carbon (SOC), bulk density (BD), soil penetration resistance (PR)] and crop yields in 6 years old continuous zero tillage (ZT) practices under maize-wheat-mungbean cropping system in a sandy loam soil of northwestern India. The highest SOC (5.73 g/kg) was observed in Zero Tillage with Residue Retention (ZT + R) plots. Zero-tillage with residue retention (ZT + R) significantly reduced the bulk density over the zero-tillage with no residue retention (ZT-R) across the soil depth. The bulk density in ZT + R was 6.5 and 10.7% lower at 0–15 cm and 15–30 cm soil depth, respectively, than under ZT-R. The penetration resistance (PR) was significantly lower in ZT + R than in ZT-R across the soil depth. Soil organic carbon (SOC) in ZT + R was 7.4% higher at 0–15 cm depth and 11.9% higher at 15–30 cm depth than under ZT-R treatment. Among PNM treatments, the sequence of treatments in SOC content was 50%N + Green Seeker (GS) >33%N + GS > RDN > 70%N + GS. The system productivity (maize equivalent yield) under ZT + R in combination with 50%BN + GS was 15.0% higher than crops grown under ZT-R with RDN. The wheat equivalent yield under the ZT + R treatment is found to be higher (5.97) in the 50%BN + GS, which was 18% higher than the recommended dose of nitrogen treatment (5.04) and 28% higher than the 70%BN + GS treatment (4.68). Results demonstrated that plots with residue retention performed better, showing a 10% increase in system productivity. The study concludes that a ZT-based system with maize-based crop rotations (MWMb) with crop residue retention and precision nitrogen management can improve soil properties and system productivity in northwestern India.

An Experimental Study of the Retention Effect of Urban Drainage Systems in Response to Grate Inlet Clogging

The rainfall drainage characteristics of urban areas result in more surface runoff compared to soil surfaces. Conventional Urban Drainage Systems, CUDs, have disadvantages when managing this surface runoff, leading to urban water circulation issues such as flooding and depletion of groundwater. The performance of CUDs varies significantly depending on the clogging of grate inlets with various debris and shapes. To address these disadvantages, Sustainable Urban Drainage Systems, SUDs, have been proposed. This study compares the drainage efficiency of the two systems; using a physical model with an artificial rainfall simulator, an experimental study was conducted with respect to clogging type, clogging ratio, and rainfall intensity. Comparative analysis of peak flow rates and the peak time demonstrates the advantages of IRDs. As a result, IRDs are applicable to the mitigation of urban water circulation problems such as inundation.

Exploring the synergistic effect of anionic and cationic fibrillated cellulose as sustainable additives in papermaking

While cationic cellulose has yet to find a place in the paper industry, manufacturers show certain interest in a more recent material: cellulose nanofibers (CNFs), generally with negative surface charge. This work suggests both to be combined to increase the mechanical properties of recycled paper while preventing the use of synthetic polyelectrolytes as retention agents. On one hand, a bleached pulp was cationized by etherification, both as-is and following mechanical refining (15,000 PFI revolutions) and submitted to high-pressure homogenization, generating two different kinds of cationic CNFs. On the other, the same pulp was submitted to an enzymatic pretreatment and high-pressure homogenization, producing a negatively charged cellulose micro/nanofiber (CMNF). Two different cellulose-based systems consisting of each type of cationic CNF and the enzymatic CMNF were applied in the papermaking of both virgin and recycled paper. This study demonstrates the effective use of the cationic CNFs as retention agents during sheet formation, which together with the enzymatic CMNFs significantly enhanced the mechanical properties of both types of paper. The study found that refining before cationization favored the retention effect, primarily due to increased surface area and charge of the cationic CNFs, where remarkable increases in the breaking length of virgin (125.1%) and recycled paper (46.5%) were reached. The synergy between cationic CNFs and enzymatic CMNFs outperformed the use of commercial polyacrylamide, a non-biodegradable polyelectrolyte. This research highlights the potential of tailored CNFs in producing high-performance papers, while promoting sustainability and offering a plausible strategy to increase paper recycling rates.

Comparative analysis and validation of posterior cruciate ligament management in mobile-bearing total knee arthroplasty: Meta-analysis and animal study.

Total knee arthroplasty (TKA) is an effective treatment for end-stage knee joint diseases. The debate over preserving or sacrificing the posterior cruciate ligament (PCL) in mobile-bearing TKA (MB TKA) still needs to be solved due to the lack of high-quality evidence, particularly meta-analyses comparing these techniques. This study aims to conduct a meta-analysis to compare the outcomes of PCL retention (CR) and PCL sacrifice (PS) in terms of clinical and functional knee scores, range of motion, complication rates, and revision rates and to validate these findings through animal experiments. A comprehensive search was conducted using MEDLINE, Cochrane, and Embase databases. Relevant studies were selected for the meta-analysis using RevMan 5.3. Additionally, an animal experiment using Sprague-Dawley rats simulated MB TKA to compare the effects of PCL retention and sacrifice surgeries. 12 studies were included in the meta-analysis. No significant differences were found between CR and PS techniques regarding HSS, KSS, KSFS, WOMAC, ROM, and medial/lateral instability. However, CR MB showed slight superiority in NKJS, while PS MB had better outcomes in complication and revision rates. In the animal study, CR rats exhibited significant early postoperative inflammation, but both groups' knee structures gradually normalized. The meta-analysis indicates that PCL retention (CR MB) and sacrifice (PS MB) have similar effects on various clinical and functional knee scores. However, PS MB is significantly better at reducing complications and revision rates. The animal experiment confirms PS MB's advantages in reducing inflammation and promoting joint recovery. Despite the strong evidence, long-term follow-up and larger-scale randomized controlled trials are necessary to confirm these findings.

Embryo retention and live birth in frozen embryo transfer cycles: a cohort study

To study the effect of embryo retention in the transfer catheter on pregnancy outcomes in frozen embryo transfer (FET) cycles. Retrospective cohort study. Tertiary-care academic medical center. This retrospective study involved a total of 39,118 women who underwent FET cycles at a tertiary-care academic medical from January 2016 to December 2022. Women were divided into a control group (n = 38,933) and embryo retention group (n = 185). The women in the embryo retention group had been propensity scores matched with those in the control group at a 1:4 ratio. The primary outcome was live birth (LB). The secondary outcomes were biochemical pregnancy, clinical pregnancy (CP), miscarriage, and ectopic pregnancy. The overall incidence of embryo retention in the transfer catheter was 0.47% (185/39,118). The pregnancy outcome in the embryo retention group after propensity score matching (PSM) was comparable to that before PSM, with a reduced likelihood of biochemical pregnancy (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.95), CP (OR, 0.81; 95% CI, 0.69-0.96), and LB (OR, 0.80; 95% CI, 0.66-0.97). In addition, the birth weight in the embryo retention group was higher compared with the control group. However, no differences were observed in terms of miscarriage, ectopic pregnancy, cesarean delivery, as well as gestational age both before and after PSM. Embryo retention in the transfer catheter decreases the chance of biochemical pregnancy, CP, and LB in FET cycles.

Light-Triggered PROTAC Nanoassemblies for Photodynamic IDO Proteolysis in Cancer Immunotherapy.

While proteolysis-targeting chimeras (PROTACs) hold great potential for persistently reprogramming the immunosuppressive tumor microenvironment via targeted protein degradation, precisely activating them in tumor tissues and preventing uncontrolled proteolysis at off-target sites remain challenging. Herein, a light-triggered PROTAC nanoassembly (LPN) for photodynamic indoleamine 2,3-dioxygenase (IDO) proteolysis is reported. The LPN is derived from the self-assembly of prodrug conjugates, which comprise a PROTAC, cathepsin B-specific cleavable peptide linker, and photosensitizer, without any additional carrier materials. In colon tumor models, intravenously injected LPNs initially silence the activity of PROTACs and accumulate significantly in targeted tumor tissues due to an enhanced permeability and retention effect. Subsequently, the cancer biomarker cathepsin B begins to trigger the release of active PROTACs from the LPNs through enzymatic cleavage of the linkers. Upon light irradiation, tumor cells undergo immunogenic cell death induced by photodynamic therapy to promote the activation of effector T cells, while the continuous IDO degradation of PROTAC simultaneously blocks tryptophan metabolite-regulated regulatory-T-cell-mediated immunosuppression. Such LPN-mediated combinatorial photodynamic IDO proteolysis effectively inhibits tumor growth, metastasis, and recurrence. Collectively, this study presents a promising nanomedicine, designed to synergize PROTACs with other immunotherapeutic modalities, for more effective and safer cancer immunotherapy.

Evidence-Based Strategies for Warm Compress Therapy in Meibomian Gland Dysfunction.

Despite promising results from technological therapies like intense pulsed light application, warm compress therapy is a mainstay in meibomian gland dysfunction (MGD). However, applying warm compresses (WC) to the eyelids is palliative rather than curative and not always dispensed with specific instructions. The range of eyelid warming treatments available and lack of clear directives for use creates uncertainty for patients accustomed to explicit dosage information. This report examines data from clinical studies across the past 20years to identify effective protocols for three types of WC-hot towel, microwavable eye mask, and self-heating eye mask (EM). Literature search for studies on WC and MGD published between 2004 and 2023 in English was conducted. Studies wherein hot towel, microwavable EM, and self-heating EM were used in a treatment arm were included and those wherein they served only as control or were used in conjunction with another intervention were excluded. 20 resulting studies were separated into 3 groups: 5 on temperature profiles of WC, 6 with single application of WC, and 9 with repeated applications. Study methods and outcomes were tabulated, and a qualitative review was performed, attending to WC protocol and efficacy, as indicated by measures of tear film, meibomian gland health, and dry eye questionnaires. Data from the aforementioned studies revealed that each method can achieve target eyelid temperature of 40°C. A single application of WC-ranging from 5 to 20min-can significantly improve tear quality, while repeated applications significantly relieve symptoms associated with dry eyes from MGD and, in most studies, significantly improve meibomian gland health. Hot towels, however, require frequent reheating to maintain eyelid temperatures above 40°C, rendering them relatively ineffective in longitudinal studies. Microwavable EM retain heat well across 10min and were found to improve tear break-up time and/or meibomian gland score. Self-heating EM have variable activation times and were typically applied for longer periods, showing benefits akin to microwavable EM in short-term studies. Studies monitoring compliance indicate greater deviation from protocol with higher application frequencies or longer-term use. Evidence suggests superior heat retention and therapeutic effects on specific contributing factors in MGD (such as Demodex) with moist-heat compress. Considering decreased patience adherence to therapy with increased usage frequencies, and balancing needs to provide succinct instructions for various compress types, an advisable strategy is for patients to apply a moist-heat generating EM (microwavable or self-heating) to each eye for at least 10min, prepared according to manufacturer's instructions.

Novel Cosmetic Ingredient CS-AA Polyion Complex and Skin Moisturizing Effect.

The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS-AA complex was examined. After analyzing the CS-AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS-AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. Validating a systematic reduction in particle size, the following order was observed: CS>CS/AA simple mixture>CS-AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS-AA complex exhibits negligible surface charge. Additionally, Fourier-transform infrared spectroscopy (FT-IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS-AA complex. Subsequently, the water-holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS-Q complex: 40.6% (1h), 20.5% (2h), and 18.7% (4h) compared to glycerin. Similarly, the CS-R complex demonstrated enhancements of 50.2% (1h), 37.5% (2h), and 33% (4h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS-Q complex and CS-R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS-Q complex and CS-R complex showed a significant increase in moisture levels after 4weeks of application. In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well-known moisturizing agent, confirmed that the CS-AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS-AA complex is a more effective ingredient than CS or AA alone in terms of efficacy.

A method to obtain the trapping energy and trapping range between hydrogen and defects at finite temperature

The binding energy between hydrogen (H) and defects in solid phase materials has been widely studied, which is of vital importance to understand the H retention effects and defect growth mechanisms. However, present studies of binding energy through density functional theory (DFT) or the molecular statics (MS) method were usually performed at 0 K, which could not take the influence of entropy into consideration. In this work, a thermodynamic method has been proposed to obtain the trapping energy between H and defects at finite temperatures. The method is based on the rate theory, which uses trapping energy (V) and trapping range (δ) to describe the trapping properties of defects. Ultimately, a parameterized H spatial cumulative distribution function at thermodynamic equilibrium state could be given. The trapping energy and trapping range parameters in the function can be determined by contrast with the results obtained from molecular dynamics or other methods. This method has been applied to calculate the trapping energies and trapping ranges of H to helium bubble and grain boundary, respectively. Further discussion has been made on the discrepancy between trapping energies obtained by this method and the conventional DFT/MS method.

Analysis of Factors Inhibiting the Implementation of Patient Medical Record Retention and Destruction Activities at Waluyo Jati Hospital

Retention and destruction of medical record documents is a management aspect in health archives to reduce files that have been stored on the filling rack for a long time. This study aims to analyze the factors that hinder the implementation of retention and destruction of medical record documents at RSUD Waluyo Jati. Qualitative descriptive method was used to analyze these factors with data collection using the 5M approach. The results showed that the main obstacles were the lack of D3 Medical Record graduates and the lack of training related to document retention and destruction. RSUD Waluyo Jati does not have an SPO (Standard Operating Procedure) related to retention and planning document retention and destruction schedules and still uses the old ICU room to store inactive documents. Other problems include the lack of shredding and file transfer equipment, and the absence of a dedicated budget for these activities. The conclusion of this study emphasizes the importance of implementing retention and destruction of medical record documents in managing efficient archives. As a solution, efforts such as increased education and training for staff, the development of comprehensive SOPs, planning document retention schedules, improving infrastructure, collaboration with third parties, and proper budget allocation are needed to ensure the effectiveness of the medical record retention and destruction process.

Real-World Retention Rate, Effectiveness, and Safety of Netakimab in the Treatment of Patients with Ankylosing Spondylitis: First Year Results of the LIBRA Post-Registration Safety Study.

: To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up. : Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan-Meier analysis. : The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator's opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis). : In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

Carrier-Free Hybrid Nanoparticles for Enhanced Photodynamic Therapy in Oral Carcinoma via Reversal of Hypoxia and Oxidative Resistance.

In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor of N, N'-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+ present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ ion and the downregulation of the HIF-1α, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.

Overcoming Cancer Drug Resistance with Nanoparticle Strategies for Key Protein Inhibition.

Drug resistance remains a critical barrier in cancer therapy, diminishing the effectiveness of chemotherapeutic, targeted, and immunotherapeutic agents. Overexpression of proteins such as B-cell lymphoma 2 (Bcl-2), inhibitor of apoptosis proteins (IAPs), protein kinase B (Akt), and P-glycoprotein (P-gp) in various cancers leads to resistance by inhibiting apoptosis, enhancing cell survival, and expelling drugs. Although several inhibitors targeting these proteins have been developed, their clinical use is often hampered by systemic toxicity, poor bioavailability, and resistance development. Nanoparticle-based drug delivery systems present a promising solution by improving drug solubility, stability, and targeted delivery. These systems leverage the Enhanced Permeation and Retention (EPR) effect to accumulate in tumor tissues, reducing off-target toxicity and increasing therapeutic efficacy. Co-encapsulation strategies involving anticancer drugs and resistance inhibitors within nanoparticles have shown potential in achieving coordinated pharmacokinetic and pharmacodynamic profiles. This review discusses the mechanisms of drug resistance, the limitations of current inhibitors, and the advantages of nanoparticle delivery systems in overcoming these challenges. By advancing these technologies, we can enhance treatment outcomes and move towards more effective cancer therapies.

Perfluorooctanoic acid efficient chain reaction degradation in multifunctional iron-sulfur mineral augmentation geobiochemical remediation system

Serious contamination of perfluorooctanoic acid (PFOA) has aroused global concern. General biotransformation or iron-based materials did not meet efficient PFOA elimination. Here, specific green and low-carbon microorganism-biochar pellets, multi-component and multifunctional iron-sulfur (FexSy) mineral pellets, and a microbe-FexSy interaction device were developed to solve this problem. The multi-scale (molecular, interface, and column scales) research method combined with the multi-process reaction model was constructed to explore PFOA removal mechanism. Results revealed that microbe-FexSy interaction achieved excellent PFOA degradation performance and retention effect, with degradation rate λ (0.213 h−1) increased by 113 % than FexSy (0.100 h−1) device. The distribution coefficient Kd and kinetic adsorption α increased by 18.54 % and 22.61 %; the fraction of kinetic sorption increased by 63.83 % in microbe-FexSy device (77 %) than alone FexSy (47 %) device. Delftia and Pseudomonas combined with Fe2+ drove an efficient cycle chain reaction for PFOA. Quantitative structure–activity relationship (QSAR) model prediction results indicated that intermediates exhibited lower biotoxicity than PFOA. Furthermore, NO3– further increased the retention effect of microbe-FexSy device for PFOA with little reaction rate fluctuation, making it promising for eliminating PFOA contamination, especially in NO3– type of groundwater. It provided an efficient technology and device based on microbe-mineral interaction in remediating PFOA-contaminated groundwater.

Preparation, optimisation, and properties of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester polymer nanomicelles

Polymer nanomicelles have the advantages of small particle size, improved drug solubility, retention effect and enhanced permeability, so they can be used in the treatment of tumour diseases. The aim of this study was to prepare and optimise a nanomicelle which can improve the solubility of insoluble drugs. Firstly, the carboxyl group of cholesterol succinic acid monoester was grafted with the side chain amino group of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CCMC), and its structure was characterized by fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Particle size has an important impact on tissue distribution, cell uptake, permeability and inhibition of tumour tissue. In this study, particle size and polydispersity index (PDI) were selected as indexes to optimise the preparation process of CCMC nanomicelles through single factor experiment, Plackett-Burman experiment, the steepest climbing experiment and response surface design experiment. The optimised CCMC nanomicelles showed an average particle size of 173.9 ± 2.3 nm and a PDI of 0.170 ± 0.053. The Cell Counting Kit-8 assay showed no significant effect on cell viability in the range of 0-1000 μg ml-1concentration. Coumarin-6 (C6) was used as a fluorescent probe to investigate the drug-carrying ability of CCMC nanomicelles. C6-CCMC showed 86.35 ± 0.56% encapsulation efficiency with a drug loading of 9.18 ± 0.32%. Both CCMC and C6-CCMC demonstrated excellent stability in different media. Moreover, under the same conditions, the absorption effect of C6 in C6-CCMC nanomicelles was significantly higher than that of free C6 while also exhibiting good sustained-release properties. Therefore, this study demonstrates CCMC nanomicelles as a promising new drug carrier that can significantly improve insoluble drug absorption.

Synthesis and Characterization of Copper-Crosslinked Carbon Dot Nanoassemblies for Efficient Macrophage Manipulation.

Nanomedicines loaded in macrophages (MAs) can actively target tumors without dominantly relying on the enhanced permeability and retention (EPR) effect, making them effective for treating EPR-deficient malignancies. Herein, copper-crosslinked carbon dot clusters (CDCs) are synthesized with both photodynamic and chemodynamic functions to manipulate MAs, aiming to direct the MA-mediated tumor targeting. First, green fluorescent CDs (g-CDs) are prepared by a one-step hydrothermal method. Subsequently, the g-CDs are complexed with divalent copper ions to form copper-crosslinked CDCs (g-CDCs/Cu), which are incubated with MAs for their manipulation. Experimental results revealed that the prepared g-CDCs/Cu displayed good aqueous dispersibility and fluorescent emission properties. The nanoassemblies can be activated to deplete the overexpressed glutathione (GSH) and generate reactive oxygen species (ROS) in the presence of laser irradiation through the combined Cu-mediated chemodynamic therapy and CD-mediated photodynamic therapy. Furthermore, the ROS produced in MAs enabled polarization of MAs to antitumor M1 phenotype, suggesting the future potential use to reverse the immunosuppressive tumor microenvironment. These results obtained from the current study suggest a significant potential to develop g-CDCs/Cu for GSH depletion, ROS generation, and MA M1 polarization as a theransotic agent to tackle cancer.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (−35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

Versatile Thermo-Sensitive liposomes with HSP inhibition and Anti-Inflammation for synergistic Chemo-Photothermal to inhibit breast cancer metastasis

Photothermal therapy (PTT) is a prospective therapeutic method for breast cancer. However, excess inflammatory response induced by PTT may aggravate tumor metastasis. Meanwhile, the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. Therefore, to attenuate the PTT-induced inflammation and inhibit tumor metastasis, a folate receptor-targeted thermo-sensitive liposome (BI-FA-LP) co-loading Berberine (BBR) and Indocyanine green (ICG) was developed. BI-FA-LP utilized enhanced permeability and retention (EPR) effect and FA receptor-mediated endocytosis to selectively accumulate at tumor, reducing off-target toxicity during the treatment. After targeting to the tumor site, BBR and ICG were released from BI-FA-LP upon laser irradiation, and ICG showed good photothermal performance, while BBR inhibited HSP70 and HSP90 expression during PTT, exerting chemo-photothermal synergetic anti-tumor effect. Moreover, BBR could suppress the PTT induced inflammation, thus inhibiting tumor metastasis and ameliorating tissue injury. Thus, this versatile liposome provided a new strategy to enhance PTT and anti-inflammatory effects for breast cancer treatment.

Influence of cascade reservoirs on the distribution, transport, and retention patterns of biogenic elements in the Jinsha River

Cascade reservoirs construction can greatly alter flow regime and sediment transport of rivers, further affecting migration and transformation processes of biogenic elements. The Jinsha River (JSR) is the China's largest hydropower base and the main runoff, sediment suspension, and nutrient source areas of the Yangtze River. However, the distribution, transport, and retention patterns of biogenic elements in the JSR are still unclear under the influence of cascade reservoirs. Therefore, monthly concentration monitoring work was conducted from November 2021 to October 2023 for various forms of carbon (C), nitrogen (N), phosphorus (P), and silicon (Si). Results showed that the concentrations and fluxes of total phosphorus (TP) and particulate phosphorus (PP) exhibited continuous decreasing trends along the reservoirs cascade, whereas N exhibited contrasting trends. The concentrations of dissolved total carbon (DTC), dissolved inorganic carbon (DIC), and total silicon also showed decreasing trends from upstream to downstream, whereas their fluxes were primarily influenced by runoff and exhibited upward fluctuations. Compared with other biogenic elements, there was a more pronounced retention effect on TP and PP by reservoirs, with average retention rates of 8.29 % and 16.01 %, respectively. Longer hydraulic retention time (HRT) can retain more TP and PP. Meanwhile, the retention rates of DTC, DIC, and particulate silicon were positively correlated with HRT, while the retention rate of dissolved silicon (DSi) showed a positive correlation with reservoir age. Moreover, the higher ratios of dissolved inorganic nitrogen to dissolved inorganic phosphorus (DIP) and DSi to DIP have occurred, resulting in apparent P limitation, particularly during the non-flood season due to lower DIP concentration. Overall, cascade reservoirs construction exists great influences on the spatial allocation, fluxes transport, and biogeochemical cycles of biogenic elements, potentially affecting the stability of rivers ecosystem along the food chain network.