High Load Research Articles

The plasma EBV DNA load with IL-6 and VEGF levels as predictive and prognostic biomarker in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein–Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up.

Revisiting the etiology and clinical characteristics of hemorrhagic polyps of the vocal fold

AbstractObjectiveBenign phonotraumatic lesions of the vocal folds (BVFLs) are typically seen in younger female patients with high vocal loads. Hemorrhagic polyps (HPs) do not fit the classic paradigm of most BVFLs, as they tend to occur in an older population, have a male predominance, and report to result from a vocal accident. We present one of the largest cohorts of HPs, to reexamine their etiology and clinical features.MethodsRetrospective cohort study, inclusive of all patients with HP managed by the senior authors between the years 2016 through 2023. Demographic data, management, phonotraumatic risk factors, pre‐ and post‐treatment VHI‐10 were reviewed. We examined patient videostroboscopy, categorized the size of the lesion, and identified any concurrent mucosal abnormality.ResultsOne hundred and eleven patients had confirmed HP, 84 males (75.7%). Thirty‐five patients were size category 1; pinpoint (28.9%), 57 were category 2; less than 1/3rd the vocal fold (45.5%), and 26 were category 3; greater than 1/3rd the vocal fold (21.5%). Ten patients (9%) had bilateral HPs. Thirty‐five patients had an additional 40 mucosal lesions in addition to the HP(s). The onset of symptoms was gradual in 60% of patients. The mean pretreatment VHI‐10 was 18.0 (SD 10.7), compared to 6.0 (SD 10.5) post‐treatment, (p < .001). 57/111 patients reported high voice demand professions or recreational activities. The average self‐reported talkative scale score was 7.6/10. Patients were managed with operative microdirect laryngoscopy and microflap excision (53.1%), in‐office clinic potassium titanyl phosphate (KTP) laser (24.3%), voice therapy alone (7.2%), and KTP in the operating room (6.3%).ConclusionsIn our cohort, most patients were male, had high vocal demands, reported gradual symptom onset, and almost a third of patients had additional BVFLs.Level of evidenceLevel 3: Retrospective cohort study.

Vertical transport of anthropogenic lead by reversible scavenging in the South Atlantic Ocean

Stable lead (Pb) isotopes have been regarded as tracers of ocean circulation, both in the present time and geological past. Here we present a new dataset of seawater Pb concentrations and isotope compositions for ten depth profiles from the South Atlantic Ocean (GEOTRACES cruises GA02 and GA10). By comparing Pb isotope data collected on the two cruises, and by modelling the distribution of Pb with an extended optimum multiparameter analysis, we find evidence of vertical transport of anthropogenic Pb pollution due to reversible scavenging. Surface to depth transfer of polluted Pb is aided by high suspended particulate matter loads at the Brazil – Malvinas Confluence and along ∼40°S in the South Atlantic. Overall, our findings caution the use of Pb isotope ratios as ventilation tracers in the South Atlantic and emphasize the importance of particle-seawater interaction for biogeochemical cycles.

Determination of the load acting on the probe by separating force and torque during FSW of AA 6060 T66

AbstractThe development of suitable welding processes is required to meet the ever-increasing demands on joining processes, particularly for lightweight construction and increasing environmental awareness. Friction stir welding (FSW) represents a promising alternative to conventional fusion welding processes, particularly for the joining of low-melting-point materials such as aluminium and magnesium alloys, which present a number of challenges, including the formation of pores and the occurrence of hot cracks. The central element of the process is the friction stir welding tool, which consists of a shoulder and a probe. The rotation and the simultaneous application of pressure during the joining process create a friction-based heat input through the tool. The excellent mechanical properties resulting from dynamic recrystallisation during the welding process are a major advantage of the process. As a result, strengths comparable to those of the base material can be achieved. However, FSW is subject to process-specific challenges, including high process forces, which result in the fabrication of complex and robust devices. Additionally, high dynamic loads on the friction stir welding tools must be considered. In many cases, the design of friction stir welding tools is based on empirical data. However, these empirical values are machine-, component- and material-specific, which often results in under- or overmatching of friction stir welding tools. Sudden probe failure, component scrap, and low process reliability are the direct consequences of undermatching. Overmatching results in enlarged tools with limited accessibility, high heat input, and high process forces, leading to component deformation. The aim of this study is to determine the load on the probe by separating the forces and torque of the shoulder and the probe in order to be able to make statements about the load acting on the probe and the resulting stress state. The knowledge of the stress state can be employed to design friction stir welding tools, both statically and dynamically, for a specific welding task. A strategy was devised to distribute the load exerted on the shoulder and probe. To this end, the length of the probe was gradually reduced between the welding tests. The investigations were carried out with a force-controlled robotized welding setup in which AA 6060 T66 sheets with a thickness of 5 mm were welded. A Kistler multicomponent dynamometer type 9139AA allows to measure the Cartesian forces to be recorded in the x-, y-, and z-directions with a sampling rate of 80 kHz. The weld seam properties were determined by visual and metallographic inspections as well as tensile and bending tests in accordance with DIN EN ISO 25239–5.

Smart Antibacterial Coatings with On‐Demand Drug Release and Real‐Time Monitoring

AbstractSmart antibacterial coatings with surface‐independent methods, on‐demand antibiotic release, and real‐time drug loading monitoring capabilities have attracted increasing interest in the fields of medical devices, antibiotics delivery platforms, and implantable devices. Addressing the complexity inherent in existing methods, this work innovates by simplifying the synthesis process and integrating aminoglycosides with metallosupramolecules to develop versatile and effective coatings. These coatings not only exhibit exceptional biological activity and efficient antibacterial properties both in vitro and in vivo, but also enable high drug loading and controlled release. Significantly, their application across various devices has demonstrated profound therapeutic effects in treating implant infections and promoting bacterial wound healing. A key advancement of these coatings is the integration of color‐changing indicators for real‐time monitoring of drug levels, enhancing the precision of wound care, and facilitating timely clinical interventions. This research marks a significant stride in the development of more accessible, bioactive, and smart antibacterial materials, opening new avenues in the field of smart medical coatings.

Enhanced Fracture Toughness of WC-CoCr Thermally Sprayed Coatings by the Addition of NiCrFeSiBC and Mo and Its Influence on Sliding Wear Behavior

Wear is a major issue in industry, particularly with metal components. Therefore, it is crucial to investigate methods that offer increased resistance to this phenomenon. In this research, three coating systems (pure WC-CoCr and WC-CoCr/NiCrFeSiBC+Mo, 88:12 and 83:17 wt.%) were thermally sprayed on an AISI 1018 steel substrate through the High-Velocity Oxygen Fuel (HVOF) process. The coatings were characterized using a field emission scanning electron microscope (FESEM) equipped with the energy dispersive spectroscope (EDS) and X-ray diffractometry (XRD). An analysis of the wear rate for ball-on-flat linear reciprocating sliding tribological tests for the coatings was also carried out. The coating microstructure presents well-dispersed NiCrFeSiBC splats. The WC-CoCr/NiCrFeSiBC+Mo, 88:12, system has the highest wear resistance, decreasing by 30.2% at high loads compared to commercial WC-CoCr CERMETs, and also exhibits the highest fracture toughness. Analysis of wear tracks shows that the material removal at all charges occurred mainly by an abrasive wear mechanism.

Association between khat chewing and high viral load in chronic hepatitis B infection

Background and aims: chronic hepatitis B infection (CHB) is a worldwide health threat that has moderate to high prevalence in Yemen. There is accumulating evidence of the hepatotoxicity of khat, which is commonly and habitually chewed in Yemen and elsewhere, but little is known in CHB. This study aimed to examine the association between khat chewing and hepatitis B virus (HBV) serum DNA level (viral load) in such cases. Methods: Between January and December 2016, a cross-sectional study was carried out on consecutively consenting 210 CHB participants (khat chewers and non-cutters) attending the hepatology clinics of two major hospitals in Sana’a city. After a structured interview, blood samples were collected for the determination of HBV markers and HBV load. Results: the study population, residing different cities in Yemen, had a median age of 36y (range = 20-72) with a 2.9:1 male to female ratio. Viral load was significantly (P<0.001) higher among khat chewers than non chewers: median (Interquartile range) = 1308 (531.5-5916.5) vs 177 (60-627) IU/ml. Khat chewing was observed, via multivariate logistic regression analysis, to be significantly (pThe0.001) and independently associated with a clinically significant high HBV load (>2000 IU/ml) even after adjustment for the studied socio-demographic and laboratory factors. Conclusion: This study suggests khat chewing, especially on a daily basis, as a potential risk factor for high viremia and, therefore, be prudently discouraged in CHB.

Enhancing structural protection of reinforced concrete structures against high dynamic loads using post-installed UHPFRC/UHPFRSC

Recently there has been an observed change in security policy across the globe which implies that humanity must prepare for hybrid and asymmetric acts of war. This security situation will result in spontaneous attacks from non-military groups. The threats include ballistic attacks from commercially available weapons, detonation of explosives, and impact of vehicles. These attacks are focused on critical infrastructures. Reinforced concrete (RC) elements with ballistic and explosion protection are of huge relevance. This requires new concepts and innovative solutions for the protection of new buildings and/or for the strengthening of existing structures. In this paper a method for the increase of structural safety is shown using Ultra-High Performance Fiber Reinforced Concrete (UHPFRC) or sprayed UHPFRC, so called UHPFRSC, as a surface layer for reinforced concrete structures. The UHPFRC/UHPFRSC is applied in thin layers of 30 - 80 mm on the protection side. The interaction of the two different cementitious materials results in increased resistance to high dynamic loads. The traditional reinforced concrete on the impact side absorbs a major fraction of the energy of impact. On the back side (protection side), tensile forces are generated by the impact, which can excellently be handled by the UHPFRC/UHPFRSC. For proof of concept of the hybrid strengthening method, tests were carried out on UHPFRC - RC composite elements. In the test campaign, ballistic tests were performed using test specimens with dimensions of 500 × 500 mm. The layer thicknesses were 120 mm reinforced concrete and 40 mm UHPFRC. Additional steel rebars in the UHPFRC layer were applied for half of the specimens. The investigation demonstrated the effectiveness of the strengthening method, showing high resistance to high-dynamic loads. This behavior is attributed to the absorption and transfer of tensile stresses by the UHPFRC, that reduces penetration depth and damage, ensuring remaining load-bearing capacity after gunfire.

Modelling the recovery time from peak loads in a full-scale horizontal flow wetland in Sicily

The aim of this study was to simulate the water flow and reactive transport of pollutants in a horizontal flow (HF) wetland to better understand the recovery time of the treatment performance for peak load events. For the simulation, the processes-based model HYDRUS and its Wetland Module is used. The system under investigation is the first stage of the 9-years old hybrid treatment wetland of a large retail store, located in Catania, Italy. For the calibration of the hydraulic model, the data of a tracer test was used. The data set of the systems is available for a seven year period including organic matter and ammonia nitrogen. The data was split into a standard event representing low loading conditions and determined peak load events with high loadings. The results show that the response time of the model correlates with the hydraulic retention time from the tracer experiment and indicates that higher peak load concentrations at the inlet of the system lead to a longer recovery time of the wetland.

Continuous Flow Microreactors for the High-efficiency Enzymatic Synthesis of 10-Hydroxystearic Acid from Oleic Acid.

Converting fatty acids into specialty chemicals is sustainable but hindered by the low efficiency and thermal instability of current oleic acid hydratases, along with mass transfer limitations in emulsion reactions. This study introduces an optimized continuous flow micro-reactor (CFMR) that efficiently transforms oleic acid at low (15 g·L-1) and high (50 g·L-1) concentrations, improving reaction efficiency and overcoming key conversion barriers. The first CFMR model showed reaction speeds surpassing traditional batch stirred tank reactors (BSTR). Optimizations were performed on three key components: liquid storage, mixer, and reaction section of the CFMR, with each round's best conditions carried into the next. This achieved a space-time yield of 597 g·L-1·d-1 at a 15 g·L-1 oleic acid load. To further enhance the yield, we optimized the emulsifier system to solve incomplete emulsification and developed a two-component feed microreactor (TCFMR) that addressed substrate and product inhibition at high loads, reaching a 91% conversion of 50 g·L-1 oleic acid in 30 minutes, with a space-time yield of 2312 g·L-1·d-1. These advancements represent significant progress in utilizing fatty acids and advancing sustainable chemical synthesis.

PH-Sensitive and Redox-Responsive Poly(Tetraethylene Glycol) Nanoparticle-Based Platform for Cancer Treatment.

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) nanoparticles were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity, and drug loading efficiency. The impact of nanoparticles on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) nanoparticles. These nanoparticles exhibit high drug loading efficiency (78.7%) and drug loading capacity (12%), with minimal changes in particle size over time in different media. In vitro experiments revealed that the nanoparticles can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of nanoparticles within cells. In conclusion, poly(tetraethylene glycol) nanoparticles hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.

SWIEET-a salt-free alternative to QuEChERS.

The efficient extraction of various analytes from a wide spectrum of matrices with organic solvents is still a great challenge in analytical chemistry. Especially polar and charged compounds are hard to extract in combination with neutral analytes of intermediate to low polarity. The QuEChERS method is often chosen and has been adapted not only to the analysis of food samples, but also to environmental matrices (soil, wastewater) or biota. In this study, we overcome major drawbacks of QuEChERS such as low recoveries of charged analytes and impairment of downstream analysis by high salt loads. The new extraction method, applicable to liquid and solid samples, is called SWIEET (sugar water isopropanol ethyl nitrile extraction technique). Phase separation of the otherwise miscible extraction solvents water and acetonitrile is achieved by sugaring-out instead of salting-out. Extraction efficiencies were greatly improved by adding isopropanol to the acetonitrile phase. The concentrations of the additives glucose and isopropanol, as well as temperature, were optimized by a design of experiment. Further improvement was achieved through electro- or double-extractions. For all sample types tested (surface water, wastewater treatment plant effluent, tomato, soil, and oats), recoveries and precision were higher with SWIEET than with the established QuEChERS method. From wastewater treatment plant effluent, 75% recovery on average were achieved with our SWIEET method compared to 37% with QuEChERS for a model analyte mixture with polarities of logDpH7 = - 5.7 - 3.5. Higher recoveries and lower standard deviations compared to QuEChERS were achieved especially for polar and charged analytes such as metformin. Handling proved to be easy, since there was no additional solid phase and no tedious weighing of salts.

Dynamic Forces and Vibrations of the Planetary Gear-Set Radial Bearings with the Roller Dimension Deviation

Double planetary gear trains (DPGTs) have high loading capacity and transmission, making them indispensable in various heavy rotating machinery applications. However, the presence of planetary gear-set radial bearing roller dimension deviation (PBRDD) from real-world manufacturing discrepancies poses a significant challenge to the dynamics of the DPGTs. Previous dynamic models often overlooked the internal excitations of the planetary gear-set radial bearing, focusing only on the single planetary gear train dynamics, rendering them inadequate for studying the impact of the PBRDD on DPGTs. Therefore, this paper proposes a coupling method integrating the PBRDD model with the DPGT dynamic model, taking into consideration the planetary gear-set radial bearing’s internal excitations, to reveal the impact of PBRDD on DPGTs’ dynamics. Specifically, the changes in roller–ring contact force and roller–cage collision force induced by PBRDD are considered. Through comprehensive simulation and experimental analyses, the accuracy of the dynamic model is assessed and its efficacy in capturing the effects of PBRDD on DPGTs’ dynamics is validated. The results show that the DPGTs’ dynamics increment with the increment of PBRDD.

Polydopamine-Modified Mesoporous Nanobottles with High Loading Capacity for Sustained Release and Retention of Kresoxim-Methyl on Foliar Surfaces

Polydopamine-Modified Mesoporous Nanobottles with High Loading Capacity for Sustained Release and Retention of Kresoxim-Methyl on Foliar Surfaces

Real-world study on the efficacy and safety of different treatment regimens in treatment-naïve CHB patients with high viral load

Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P < 0.05). There were no significant differences in HBsAg loss among the four groups, but the HBeAg seroconversion rate was significantly higher in the TAF group. The ALT normalization rate was significantly higher in the TAF group (72.2%) compared to the others at 48 weeks (P < 0.05). In treatment-naïve CHB patients with high viral load, combination therapy was not superior to TDF or TAF monotherapy in virological response. Patients treated with TDF or TAF showed superior virological response compared to those treated with ETV. The TAF group demonstrated superiority in terms of ALT normalization and HBeAg seroconversion.

Larger shrubs can maintain high infiltration and evapotranspiration rates in experimental biofiltration systems impacted by high sediment loads

Biofiltration systems can fail over time due to clogging by fine sediments in stormwater. Infiltration can be maintained by plant roots, but species selection for biofiltration to date has largely been driven by pollutant removal efficiency and tolerance of conditions. As a result, plant species diversity in biofilters is typically low and dominated by sedges and rushes. Increased use of woody species could in theory improve plant diversity, aesthetic appeal, infiltration under high sediment loads and volumetric runoff reduction via higher evapotranspiration, without jeopardising nutrient pollutant removal. We tested whether shrubs could maintain infiltration and evapotranspiration in biofiltration profiles treated with a high sediment load, by comparing them with biofilters subjected to tap water without sediment. Following sediment application, biofilter columns planted with shrubs with high total biomass and total root length showed higher infiltration and evapotranspiration than those receiving tap water. These results indicate that shrub species are likely to alleviate clogging and increase stormwater retention in biofiltration systems. However, shrubs with a high root diameter also had low total biomass and total root length and showed 33–51 % lower infiltration rates after sediment application compared with those receiving tap water. As all shrubs had higher root diameters than typical sedges and rushes, we suggest that shrubs need a combination of higher total biomass, total root length and average root diameter to effectively maintain infiltration. While shrubs which maintained infiltration had traits associated with high nutrient removal, nutrient removal efficiency of shrubs needs to be quantified. Although root traits were related to maintenance of infiltration, above-ground stems likely created flow pathways through sediment which requires further investigation. Overall, selecting shrub species with high total biomass has the potential to maintain infiltration and increase evapotranspiration in biofiltration systems impacted by high sediment loads.

Influence of variable enhanced LIVC miller cycle coupled with high compression ratio on the performance and combustion of a supercharged spark ignition engine

A novel variable enhanced late intake valve closing (LIVC) Miller cycle with asynchronous valve opening was proposed. Relevant tests were carried out in a supercharged spark ignition (SI) engine with high compression ratio, which mainly included the effects of variable valve timing on performance and combustion characteristics, as well as the comparison with the baseline engine. The purpose of this study was to explore the effect of different intake and exhaust opening timing on the performance and combustion characteristics of the enhanced LIVC Miller cycle with asynchronous valve opening, and further explore the energy saving potential of this Miller cycle. The results showed that the application of variable enhanced Miller cycle effectively improved the anti-knock ability and pumping loss of the engine with high compression ratio. On the one hand, the optimization of pumping loss substantially improved the fuel economy under small load conditions. On the other hand, better combustion performance and air-fuel ratio could be achieved at medium and high loads. Meanwhile, the exhaust valve should be opened as earlier as possible to achieve the best fuel economy. Correspondingly, under optimal valve timing, compared with the baseline engine, the asynchronous intake valve opening variable enhanced Miller cycle engine with high compression ratio had a fuel economy optimization of more than 3.5 % under all loads, and the maximum fuel economy optimization was 12.74 % under the condition of 11 bar.

Identification of antibody targets associated with lower HIV viral load and viremic control.

High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1-2 years after infection. Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1-2 years after HIV infection). The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status. We identified HIV antibody targets associated with lower VL and HIV controller status 1-2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL.

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-basedchemotherapy plus Gossypol with pro-apoptotic effects displays asynergisticeffect forkillingtumorcells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. Inthe patient-derived tumor xenograft (PDX)model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells.

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64nm) and a more negative zeta potential (-36.94 ± 0.32mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.