Association between movement behavior patterns and cardiovascular risk among Chinese adults aged 40-75: a sex-specific latent class analysis.

BACKGROUND: Cardiovascular disease (CVD) is a major global health threat, particularly in China, contributing to over 40% of deaths. While sleep behaviors, sedentary behaviors, and physical activities are recognized as independent lifestyle risk factors for CVD, there remains limited understanding of specific movement behavior patterns and their CVD risks, especially considering sex-specific differences. This study examines movement behavior patterns among Chinese adults (40-75) and their associations with cardiovascular risk, with a focus on sleep, physical activity (PA), and sedentary behavior (SB). METHODS: Data pertaining to 13,465 male participants and 15,613 female participants, collected from the Chronic Disease and Risk Factor Surveillance Survey in Nanjing from February 2020 to December 2022. The latent class analysis method was employed to identify underlying movement patterns across sexes. Multinomial logistic regression models assessed CVD risk, and the China-PAR model calculated 10-year risk. RESULTS: Three male and four female movement patterns emerged. Active Movers (17.10% males, 5.93% females) adhered to PA recommendations but had poorer sleep quality. Moderate Achievers (61.42% males, 45.32% females) demonstrated moderate behavior. Sedentary Sleepers (21.48% males, 10.20% females) exhibited minimal PA but good sleep. Female Moderate Physical Activity (MPA) Dominant Movers demonstrated a prevalent adherence to recommended MPA levels. Active movers had the lowest CVD risk. After adjusting for potential confounders, moderate achievers (OR = 1.462, 95% CI 1.212, 1.764) and sedentary sleepers (OR = 1.504, 95% CI 1.211, 1.868) were both identified as being associated with a high-risk of cardiovascular diseases (CVDs) compared to active movers in males, demonstrating a similar trend for intermediate risk. Such associations were not statistically significant among females. CONCLUSIONS: Our study revealed sex-specific movement patterns associated with CVD risks among middle-aged Chinese adults. We suggest that adopting an active movement behavior pattern, characterized by meeting or exceeding recommended levels of vigorous physical activity (VPA) and reducing sedentary behavior, is beneficial for all middle-aged adults, particularly males. An active lifestyle could help counteract the adverse effects of relatively poor sleep quality on the risk of developing CVD in this population. Integrating sleep, PA, and SB information provides a holistic framework for understanding and mitigating CVD risks.

Production of single cell protein rich in potassium by Nectaromyces rattus using biogas slurry and molasses.

Single-cell protein (SCP) is a vital supplement for animal protein feed. This study utilized biogas slurry and sugarcane molasses to ferment Nectaromyces rattus for the production of SCP. The optimal batch fermentation conditions were obtained in a 5L jar with a tank pressure of 0.1 MPa, an initial speed of 300 rpm, and an inoculum volume of 30%. The highest cell dry weight concentrations of the fed-batch fermentation without reflux and the fed-batch fermentation with reflux were 46.33 g/L and 29.71 g/L, respectively. The nitrogen conversion rates (47.05% and 44.12%) and the cell yields of total organic carbon (1 g/g and 1.17 g/g) of both fermentation modes were compared. The SCP contained 42.32% amino acids. Its high concentrations of potassium (19859.96 mg/kg) and phosphorus (7310.44 mg/kg) present a novel approach for the extraction of these essential nutrients from biogas slurry. The enrichment of K was related to the H+ efflux and sugar transport.

Boosting External Quantum Efficiency to 12.0 % of an Ultraviolet OLED by Engineering the Horizontal Dipole Orientation of a Hot Exciton Emitter.

Currently, much research effort has been devoted to improving the exciton utilization efficiency and narrowing the emission spectra of ultraviolet (UV) fluorophores for organic light-emitting diode (OLED) applications, while almost no attention has been paid to optimizing their light out-coupling efficiency. Here, we developed a linear donor-acceptor-donor (D-A-D) triad, namely CDFDB, which possesses high-lying reverse intersystem crossing (hRISC) property. Thanks to its integrated narrowband UV photoluminescence (PL) (λPL: 397 nm; FWHM: 48 nm), moderate PL quantum yield (ϕPL: 72 %, Tol), good triplet hot exciton (HE) conversion capability, and large horizontal dipole ratio (Θ//: 92 %), the OLEDs based on CDFDB not only can emit UV electroluminescence with relatively good color purity (λEL: 398 nm; CIEx,y: 0.161, 0.040), but also show a record maximum external quantum efficiency (EQEmax) of 12.0 %. This study highlights the important role of horizontal dipole orientation engineering in the molecular design of HE UV-OLED fluorophores.

A Natural-Position X-Ray for Evaluating Cervical Vertebra Physiology Curvature Before and After Conservative Treatment.

BACKGROUND Abnormal physiological curvature is one of the symptoms of early cervical spondylosis. An X-ray taken with the patient standing in a natural position can best reflect the real cervical vertebra physiological curvature. The purpose of this research was to study the value of natural-position X-ray in evaluating cervical vertebra physiology curvature before and after conservative treatment. MATERIAL AND METHODS This study included 135 participants of different ages diagnosed with cervical disease and who received conservative treatment for more than 12 months. The natural- and regular-position X-rays were performed before and after treatment. The positive change of D value in Borden's measurement and C2~7 Cobb angle should be recognized as an improvement of cervical vertebra physiology curvature. RESULTS Before treatment, the C2~7 Cobb angle of the regular-position group was larger than that of natural-position group. After treatment, the C2~7 Cobb angle of the natural-position group was larger than that of the regular-position group, and the D value increased after treatment in both groups. The effective rate of cervical physiological curvature of the natural-position group was higher than that of the regular-position group. CONCLUSIONS Natural-position X-ray has greater accuracy in evaluating cervical vertebra physiology curvature before and after conservative treatment compared with regular-position X-ray.

Low C/N promotes stable partial nitrification by enhancing the cooperation of functional microorganisms in treating high-strength ammonium landfill leachate.

Partial nitrification is an effective process for treating high-strength ammonium landfill leachate with low C/N ratio, for the cooperation with denitrification can save almost 40% carbon addition in biological nitrogen removal. However, high ammonia loading often causes the instability of partial nitrification process. Less carbon addition can promote the stability of partial nitrification and increase the nitrite accumulation ratio (NAR). Nevertheless, the microbial mechanisms within remain further elusive. In this study, two laboratory-scale sequencing batch reactors were constructed and operated for 125 days, which were fed with ammonia synthetic wastewater with C/N of 0.6 (CN system) and C/N of 0.0 as the control (N system). CN system performed more stably and had the highest NAR of 100%. Extracellular polymeric substances (EPS) generated from carbon source provided spatial and nutrient niches to tighten the cooperation of functional microorganisms, thus, enhanced the stability and efficiency of partial nitrification. Thauera was the dominant denitrifier in CN system. Nitrosomonas was one of the most important autotrophic ammonia oxidizing bacteria, while Paracoccus and Flavobacterium were the main heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria in CN system. The enrichment of HN-AD bacteria outcompeted nitrite oxidizing bacteria (NOB), therefore leaded to higher nitrite accumulation in CN system. The findings of this study may be conducive to increasing the understanding of the microbial collaboration mechanisms of partial nitrification, thereby provides theoretical support for the improvement of biological nitrogen removal technology.

Comparison of the Use of Magnetic Resonance Imaging of Partial Anterior Cruciate Ligament Tears Using Maximum Knee Flexion in the Lateral Decubitus Position with Routine Knee Positioning.

BACKGROUND This study assessed magnetic resonance imaging (MRI) of acute and chronic partial anterior cruciate ligament (ACL) tears using maximum knee flexion in the lateral decubitus position compared with routine knee positioning in 204 patients at a single center. MATERIAL AND METHODS Based on the time interval from injury to MRI examination, the 204 patients in this study were divided into 3 groups: subacute (6 weeks to 3 months), intermediate (3 months to 1 year), and chronic (>1 year). All patients received both routine MRI (MRI R) and maximum knee flexion in the lateral decubitus position MRI (MRI S) examination, followed by knee arthroscopy. Three radiologists blinded to patient groups evaluated the MRI scans and made a diagnosis. Results of knee arthroscopy were referenced as the criterion standard. The sensitivity and specificity of MRI R and MRI S groups were calculated and compared. RESULTS The MRI S diagnostic rate was comparable to that of knee arthroscopy. MRI S had significantly higher sensitivity than MRI R for partial ACL tears, especially in the intermediate group (P<0.01). CONCLUSIONS MRI of partial ACL tears using maximum knee flexion in the lateral decubitus position improved the diagnostic rate relative to routine MRI examination, particularly in patients in the intermediate group.

Robust registration for ultra-field infrared and visible binocular images.

The ultra-field infrared and visible image registration is a challenging task due to its nonlinear imaging and multi-modal image features. In this paper, a robust registration method is proposed for the ultra-field infrared and visible images. First, control points are extracted utilizing phase congruency and optimized based on the guidance map, which is proposed according to significant structures information. Second, ROI pair matching is accomplished based on epipolar curve. Its effect is equivalent to a search window that is popular in methods with the standard field of view, and it can overcome the content differences in the search window caused by nonlinear imaging and vision disparity. Third, a descriptor, named multiple phase congruency directional pattern (MPCDP), is established and composed of distribution information and main direction. The phase congruency amplitudes are encoded as binary patterns, and then they are represented as weighted histogram for distribution information. Six pairs of ultra-field infrared and visible images are employed for registration experiments, and the results demonstrate that the performance of the proposed is robust and accurate in five types of ultra-field scenes and two different camera relationships.

Value of CT and three-dimensional reconstruction revealing specific radiological signs for screening causative high jugular bulb in patients with Meniere's disease.

BACKGROUND: The aim of the present study was to investigate the pathological features of vestibular aqueduct (VA) related high jugular bulb (HJB) and explore the possible cause-consequence relation between HJB and endolymphatic hydrops (EH), and the potential specific radiological signs for screening causative HJB in Meniere's disease (MD). METHODS: High-resolution computed tomography (HRCT) and three-dimensional reconstruction (3DRC) were used to detect the anatomical variables associated with VA and jugular bulb (JB) in hydropic and non-hydropic ears. The presence or absence of EH in the inner ear was determined by gadopentetate dimeglumine-enhanced magnetic resonance imaging. The presence of different types of HJB, the anatomical variables of the VA and JB and the three types of anatomical relationship between the VA and HJB were compared between the hydropic and non-hydropic ears using the χ2 or Fisher's exact tests. P < 0.05 was considered to indicate a statistically significant difference. RESULTS: JB was classified as: Type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (PSCC); type 3, between the inferior margin of the PSCC and the inferior margin of the internal auditory canal (IAC); type 4, above the inferior margin of the IAC. There were no significant differences in the presence of types 1, 2 and 3 JB between two groups. The presence of type 4 JB, average height of the JB and prevalence of the non-visualization of the VA in CT scans showed significant differences between two groups. The morphological pattern between the JB and VA revealing by 3DRC was classified as: Type I, the JB was not in contact with the VA; type II, the JB was in contact with the VA, but the latter was intact without obstruction; type III, the VA was obliterated by HJB encroachment. There were no significant differences in the presence of type I and II between two groups. Type III was identified in 5 hydropic ears but no non-hydropic ears, with a significant difference observed between the two groups. CONCLUSION: The present results showed that JB height and non-visualization of the VA on Pöschl's plane could render patients susceptible to the development of EH. A jugular bulb reaching above the inferior margin of the IAC (type 4 JB) could obstruct VA, resulting in EH in a few isolated patients with MD. VA obliteration revealed by 3DRC, as a specific radiological sign, may have the potential for screening causative HJB in MD.

The role of endogenous and exogenous hydrogen in the microbiology of biogas production systems.

Anaerobic digestion is an effective process for the treatment of organic solid waste and wastewater and the production of biogas, which is a clean energy source. The carbon dioxide in the biogas can be converted into methane using hydrogen generated from water electrolysis through an approach referred to as power-to-gas. Recently, hydrogen has been added to digesters as an in-situ or ex-situ biogas upgrade to reduce the levels of carbon dioxide. Biogas production systems consist of microbial complexes with highly organized microorganisms in different niches, which can either produce or consume hydrogen. However, the produced endogenous hydrogen should be constantly consumed to maintain a low hydrogen partial pressure. This review addresses the biochemical processes of anaerobic digestion and hydrogen-related microorganisms, including fermentative acid-producing bacteria, syntrophic organic acid degrading bacteria, syntrophic acetate-oxidizing bacteria, homoacetogens, hydrogenotrophic methanogens, and newly reported hydrogen-dependent methylotrophic methanogens. This study also investigates (1) the role of endogenous hydrogen as an intermediate metabolite and of interspecies electron transfer in anaerobic digestion, (2) effects of exogenous hydrogen addition on microbial community structure and metabolic processes, and (3) recent developments regarding in-situ and ex-situ biogas upgrading systems via hydrogen addition.

TMPRSS3 regulates cell viability and apoptosis processes of HEI-OC1 cells via regulation of the circ-Slc4a2, miR-182 and Akt cascade.

BACKGROUND: The present study aimed to investigate the functions and regulation mechanism of the transmembrane protease, serine 3 (TMPRSS3), which plays an important role in sensorineural hearing loss. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, comprising auditory-related cells, were used in the present study. An overexpression vector and small hairpin RNA target on TMPRSS3 were designed and transfected into HEI-OC1 cells. Circular RNA (circRNA) sequencing was conducted and expression profiles were obtained. The circular structure of circRNAs was validated with a polymerase chain reaction and Sanger sequencing using convergent and divergent primers. RESULTS: Overexpression of TMPRSS3 increased cell viability, whereas suppression of TMPRSS3 increased the percentage of apoptotic cells and decreased cell viability, compared to the control group. circRNA sequencing provided expression profiles indicating that the overexpression of TMPRSS3 increased the expression level of 195 circRNAs. Results of GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) studies indicated that the circRNAs are focused on the RAS signaling pathway. The pathway, circ-Slc41a2 (chr10: 82744115|82767120), miR-182 and Akt, might comprise one of the key cascades of TMPRSS3. CONCLUSIONS: TMPRSS3 is an important molecule in the regulation of cell viability and cell apoptosis of HEI-OC1 cells. Its functions are dependent on the circ-Slc41a2, miR-182 and Akt cascade.

Plane chessboard-based calibration method for a LWIR ultra-wide-angle camera.

A method is proposed to calibrate the long-wave infrared ultra-wide-angle camera in this paper. In addition, a novel calibration chessboard is designed and an advanced chessboard corner positioning method is adopted to improve the calibration precision. The designed calibration chessboard can achieve high thermal infrared contrast and exhibits outstanding stability, which is made of a thermoelectric semiconductor refrigeration device. The proposed subpixel corner positioning method can accurately locate the corners on the calibration chessboard according to the characteristics of the infrared image and the checkerboard pattern. Both the principle of the proposed infrared chessboard and the subpixel corner positioning procedure were presented, and the calibration experiment showed that the mean reprojection error and the root mean square error were reduced to 0.32 pixel and 0.39 pixel, respectively. Comparison studies were also performed to verify the calibration effect of the proposed method, and the possibilities of camera calibration error of the proposed method were analyzed.

Differences of methanogenesis between mesophilic and thermophilic in situ biogas-upgrading systems by hydrogen addition.

To investigate the differences in microbial community structure between mesophilic and thermophilic in situ biogas-upgrading systems by H2 addition, two reactors (35 °C and 55 °C) were run for four stages according to different H2 addition rates (H2/CO2 of 0:1, 1:1, and 4:1) and mixing mode (intermittent and continuous). 16S rRNA gene-sequencing technology was applied to analyze microbial community structure. The results showed that the temperature is a crucial factor in impacting succession of microbial community structure and the H2 utilization pathway. For mesophilic digestion, most of added H2 was consumed indirectly by the combination of homoacetogens and strict aceticlastic methanogens. In the thermophilic system, most of added H2 may be used for microbial cell growth, and part of H2 was utilized directly by strict hydrogenotrophic methanogens and facultative aceticlastic methanogens. Continuous stirring was harmful to the stabilization of mesophilic system, but not to the thermophilic one.

Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.

Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only. Gene transfection in both lungs and s.c. tumors was significantly higher with our polymer compared to PEI. In addition, the Dox + IL-36γ/POEG-st-Pmor not only could bring improved anti-metastatic effect but synergistically enhance the type I immune response by increasing the IFN-γ positive CD4+ and CD8+ T cells and simultaneously decreasing the immunosuppressive myeloid-derived suppressor cells in the lung. POEG-st-Pmor may represent a simple and effective delivery system for an optimal chemo-gene combination therapy.

Recovery of unstable digestion of vegetable waste by adding trace elements using the bicarbonate alkalinity to total alkalinity ratio as an early warning indicator.

Vegetable waste (VW) is highly perishable and susceptible to acidification during anaerobic digestion, which inhibits biogas production. Effective process monitoring, diagnosis and control are necessary to maintain stable anaerobic digestion at a high organic loading rate (OLR). Continuous mesophilic digestion was conducted at OLRs of 0.5, 1.0, 1.5, 2.0, 3.0, 3.5 and 4.0 g volatile solids (VS)/(L d) with effluent recirculation (ER) in a reactor with total volume of 70 L. The effectiveness of three early warning indicators was validated. The ability of trace elements (TEs) (Fe, Co and Ni) to recover unstable VW digestion systems was evaluated. The results showed that the ratio of bicarbonate alkalinity (BA) to total alkalinity (TA) was a more effective warning indicator than the ratios of methane (CH4) to carbon dioxide and volatile fatty acids (VFAs) to TA. When the ratio of BA/TA was lower than 0.9, the digestion system tended to be unstable. ER maintained a stable OLR of 1.5 g VS/(L d). The addition of TEs achieved a maximum stable OLR of 3.5 g VS/(L d) with an average volumetric biogas production rate of 1.91 L/(L d). Severe VFAs accumulation and unrecoverable instability occurred at an OLR of 4.0 g VS/(L d). The supplementation of ammonium bicarbonate was not useful for the recovery of the unstable system when the OLR was greater than 3.5 g VS/(L d) for the digestion of VW. The specific methane production was approximately 340 L/kg VS during the stable period with a digestion efficiency of 85%.

Improved Cancer Immunochemotherapy via Optimal Co-delivery of Chemotherapeutic and Immunomodulatory Agents.

It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX). Although antitumor immune responses were enhanced with a PTX-loaded nanocarrier, the accumulation of myeloid-derived suppressor cells (MDSCs) was also significantly increased, which may limit the overall efficacy of therapy. In the present work, we developed an improved dual-functional nanocarrier (PEG5k-Fmoc-NLG2) to co-load PTX and sunitinib (SUN, a multitarget receptor tyrosine kinase inhibitor) for improved cancer immunochemotherapy. We found that the recruited MDSCs negatively impacted the overall antitumor activity of the PTX-loaded PEG-NLG nanocarrier. Mechanistic study suggests that this is likely attributed to the PTX-mediated induction of a number of chemokines that are involved in the recruitment of MDSCs. We have further shown that the induction of these chemokines was drastically blocked by SUN. Co-delivery of PTX and SUN via the PEG5k-Fmoc-NLG9192 nanocarrier led to a further improvement in the therapeutic efficacy with a concomitant reduction in MDSCs.

LESS: Link Estimation with Sparse Sampling in Intertidal WSNs.

Deploying wireless sensor networks (WSN) in the intertidal area is an effective approach for environmental monitoring. To sustain reliable data delivery in such a dynamic environment, a link quality estimation mechanism is crucial. However, our observations in two real WSN systems deployed in the intertidal areas reveal that link update in routing protocols often suffers from energy and bandwidth waste due to the frequent link quality measurement and updates. In this paper, we carefully investigate the network dynamics using real-world sensor network data and find it feasible to achieve accurate estimation of link quality using sparse sampling. We design and implement a compressive-sensing-based link quality estimation protocol, L E S S , which incorporates both spatial and temporal characteristics of the system to aid the link update in routing protocols. We evaluate L E S S in both real WSN systems and a large-scale simulation, and the results show that L E S S can reduce energy and bandwidth consumption by up to 50 % while still achieving more than 90 % link quality estimation accuracy.

Lymphoma Immunochemotherapy: Targeted Delivery of Doxorubicin via a Dual Functional Nanocarrier.

Chemotherapy drug (paclitaxel, PTX) incorporated in a dual functional polymeric nanocarrier, PEG-Fmoc-NLG, has shown promise as an immunochemotherapy in a murine breast cancer model, 4T1.2. The formulation is composed of an amphiphilic polymer with a built-in immunotherapy drug NLG919 that exhibits the immunostimulatory ability through the inhibition of indoleamine 2,3-dioxygenase 1 (IDO-1) in cancer cells. This work evaluates whether the PEG-derivatized NLG polymer can also be used for delivery of doxorubicin (Dox) in treatment of leukemia. The Dox-loaded micelles were self-assembled from PEG-Fmoc-NLG conjugate, which have a spherical shape with a uniform size of ∼120 nm. In cultured murine lymphocytic leukemia cells (A20), Dox-loaded PEG-Fmoc-NLG micelles showed a cytotoxicity that was comparable to that of free Dox. For in vivo studies, significantly improved antitumor activity was observed for the Dox/PEG-Fmoc-NLG group compared to Doxil or the free Dox group in an A20 lymphoma mouse model. Flow cytometric analysis showed that treatment with Dox/PEG-Fmoc-NLG micelles led to significant increases in the numbers of both total CD4+/CD8+ T cells and the functional CD4+/CD8+ T cells with concomitant decreases in the numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg). Dox/PEG-Fmoc-NLG may represent a promising immunochemotherapy for lymphoma, which warrants more studies in the future.

Improved Micellar Formulation for Enhanced Delivery for Paclitaxel.

We have previously improved the bioactivity of PEG5k-FTS2 system by incorporating disulfide bond (PEG5k-S-S-FTS2) to facilitate the release of farnesyl thiosalicylic acid (FTS).1 Later, fluorenylmethyloxycarbonyl (Fmoc) moiety has been introduced to PEG5k-FTS2 system (PEG5k-Fmoc-FTS2) in order to enhance drug loading capacity (DLC) and formulation stability.2 In this study, we have brought in both disulfide linkage and Fmoc group to PEG5k-FTS2 to form a simple PEG5k-Fmoc-S-S-FTS2 micellar system. PEG5k-Fmoc-S-S-FTS2 conjugate formed filamentous micelles with a ∼10-fold decrease in critical micellar concentration (CMC). Compared with PEG5k-Fmoc-FTS2, our novel system exhibited further strengthened DLC and colloidal stability. More FTS was freed from PEG5k-Fmoc-S-S-FTS2 in treated tumor cells compared to PEG5k-Fmoc-FTS2, which was correlated to an increased cytotoxicity of our new carrier in these cancer cells. After loading Paclitaxel (PTX) into PEG5k-Fmoc-S-S-FTS2 micelles, it showed more potent efficiency in inhibition of tumor cell proliferation than Taxol and PTX-loaded PEG5k-Fmoc-FTS2. PTX release kinetics of PTX/PEG5k-Fmoc-S-S-FTS2 was much slower than that of Taxol and PTX/PEG5k-Fmoc-FTS2 in normal release medium. In contrast, in glutathione (GSH)-containing medium, PTX in PEG5k-Fmoc-S-S-FTS2 micelles revealed faster and more complete release. Pharmacokinetics and tissue distribution study showed that our PEG5k-Fmoc-S-S-FTS2 system maintained PTX in circulation for a longer time and delivered more PTX to tumor sites with less accumulation in major organs. Finally, PTX-loaded PEG5k-Fmoc-S-S-FTS2 micelles resulted in a superior therapeutic effect in vivo compared to Taxol and PTX formulated in PEG5k-Fmoc-FTS2 micelles.

Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier.

To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles). DOX/PSSN10 micelles displayed spherical morphology with a size of ∼170 nm. DOX was effectively loaded into PSSN10 micelles with a loading efficiency of 84.0%. In vitro DOX release studies showed that rapid drug release could be achieved in the highly redox environment after intracellular uptake by tumor cells. In 4T1.2 tumor-bearing mice, DOX/PSSN10 micelles exhibited greater accumulation of DOX and NLG in the tumor tissues compared with other organs. The PSSN10 carrier dose-dependently enhanced T-cell immune responses in the lymphocyte-Panc02 co-culture experiments, and significantly inhibited tumor growth in vivo. DOX/PSSN10 micelles showed potent cytotoxicity in vitro against 4T1.2 mouse breast cancer cells and PC-3 human prostate cancer cells comparable to that of DOX. In 4T1.2 tumor-bearing mice, DOX/PSSN10 mixed micelles (5 mg DOX/kg, iv) was more effective than DOXIL (a clinical formulation of liposomal DOX) or free DOX in inhibiting the tumor growth and prolonging the survival of the treated mice. In addition, a more immunoactive tumor microenvironment was observed in the mice treated with PSSN10 or DOX/PSSN10 micelles compared with the other treatment groups. In conclusion, systemic delivery of DOX via PSSN10 nanocarrier results in synergistic anti-tumor activity.

PEG-Fmoc-Ibuprofen Conjugate as a Dual Functional Nanomicellar Carrier for Paclitaxel.

Ibuprofen is a kind of nonsteroidal anti-inflammatory drug (NSAIDs), and it is considered to possess some antitumor effect. In this study, a novel nanomicellar carrier based on PEG-derivatized ibuprofen, PEG2K-Fmoc-Ibuprofen (PEG2K-FIbu), was developed for delivery of anticancer agents such as paclitaxel (PTX). This conjugate readily forms stable mixed micelles with PTX with a relatively high PTX loading capacity of 67%. The release of PTX from PTX-loaded PEG2K-FIbu micelles was significantly slower than that from Taxol formulation. PTX-loaded PEG2K-FIbu micelles and Taxol showed a comparable in vitro cytotoxicity. Importantly, PTX-loaded PEG2K-FIbu micelles demonstrated a much more pronounced in vivo therapeutic efficacy compared with Taxol with respect to both inhibition of tumor growth and animal survival. Our system may represent an attractive dual-functional delivery system to achieve synergistic activity with PTX while minimizing the carrier-associated toxicity.