Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.

Formation of a two-dimensional helical square tube ice in hydrophobic nanoslit using the TIP5P water model.

In extreme and nanoconfinement conditions, the tetrahedral arrangement of water molecules is challenged, resulting in a rich and new phase behavior unseen in bulk phases. The unique phase behavior of water confined in hydrophobic nanoslits has been previously observed, such as the formation of a variety of two-dimensional (2D) ices below the freezing temperature. The primary identified 2D ice phase, termed square tube ice (STI), represents a unique arrangement of water molecules in 2D ice, which can be viewed as an array of 1D ice nanotubes stacked in the direction parallel to the confinement plane. In this study, we report the molecular dynamics (MD) simulations evidence of a novel 2D ice phase, namely, helical square tube ice (H-STI). H-STI is characterized by the stacking of helical ice nanotubes in the direction parallel to the confinement plane. Its structural specificity is evident in the presence of helical square ice nanotubes, a configuration unseen in both STI and single-walled ice nanotubes. A detailed analysis of the hydrogen bonding strength showed that H-STI is a 2D ice phase diverging from the Bernal-Fowler-Pauling ice rules by forming only two strong hydrogen bonds between adjacent molecules along its helical ice chain. This arrangement of strong hydrogen bonds along ice nanotube and weak bonds between the ice nanotube shows a similarity to quasi-one-dimensional van der Waals materials. Ab initio molecular dynamics simulations (over a 30 ps) were employed to further verify H-STI's stability at 1 GPa and temperature up to 200 K.

Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial.

BACKGROUND: Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP. METHODS: Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF). DISCUSSION: The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 . Registered on 5 January 2023.

Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies.

BACKGROUND: Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders. OBJECTIVE: To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders. METHODS: Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool. CONCLUSION: This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.

Furan-based fluorescent probe free radical capture membrane: Analysis of RO2 radical composition and transformation mechanism in urban atmosphere.

Peroxyl radicals (RO2) are important components of atmospheric radical cycling and generation, but their formation, distribution and evolution mechanisms in the atmospheric environment have not been investigated. In this paper, we propose a novel atmospheric RO2 radical trapping membrane that can trap low carbon number (Rc ≤ 5) RO2 radicals and identify their R-group structures by fluorescence spectroscopy and chromatography. We also analyzed the composition and evolution mechanism of RO2 species under different meteorological conditions in the atmospheric environment of Lanzhou, China, to provide scientific support for the treatment and research of atmospheric chemical pollution.

DPM2 serve as novel oncogene and prognostic marker transactivated by ESR1 in breast cancer.

Breast cancer (BRCA) is the most common malignancies worldwide with increasing rate. Dolichol phosphate mannose synthase (DPMS) is a critical mannosyltransferase involved in the posttranslational modification of proteins. At present, there is limited knowledge regarding the function of DPMS in breast cancer. In this study, silica analysis in multiple datasets found that dolichyl-phosphate mannosyltransferase subunit 2 (DPM2) is an unfavorable prognostic marker, suggesting its oncogenic role. Cell counting kit-8 and apoptosis assays show that DPM2-silenced cancer cells exhibit decreased growth potential and enhanced cell death rate. Further, transwell and wound healing assays show reduced invasion and migration capabilities in DPM2 knockdown groups, xenograft nude mice model demonstrated smaller tumor volume in DPM2 silenced BC cells. Then, the underlying downstream mechanism of DPM2 in BC was predicted and analyzed, highlighting classical tumorigenic pathways like JAK/STAT signaling pathway and oxidative phosphorylation activated in the cancer group. Finally, ChIP-seq analysis, expression correlation analysis, inhibitor treatment, and dual luciferase assays show that DPM2 is transcriptionally activated by estrogen receptor1 (ESR1). The results show that high expression of DPM2 mRNA is significantly correlated with shorter overall survival (OS) and disease-free survival (DFS) in breast cancer patients, and in vitro knockdown of DPM2 can significantly inhibit the malignant phenotypes of cells, including proliferation, invasion, migration, and apoptosis. These results suggest that DPM2 may play an important role in breast cancer. Altogether, we first uncovered the tumorigenic and prognostic role of DPM2 in breast cancer, cellular assays, and bioinformatics analysis highlighted DPM2 as oncogene via inhibited cancer-related signaling pathways in breast cancer. Besides, DPM2 is transcriptionally activated by ESR1, the signaling axis of ESR1/DPM2 provides a new strategy for BC-targeted therapy.

Potential chemoprotective effects of active ingredients in Salvia miltiorrhiza on doxorubicin-induced cardiotoxicity: a systematic review of in vitro and in vivo studies.

Background: Recently, attention has been paid to the protective properties of active ingredients in Salvia miltiorrhiza (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on in vitro and in vivo models of doxorubicin-induced cardiotoxicity (DIC). Methods: According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant in vitro and in vivo studies on "the role of AISM on DIC" published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias. Results: Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in Salvia miltiorrhiza were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, etc. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool. Conclusion: This systematic review demonstrated that AISM have chemoprotective effects on DIC in vivo and in vitro models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.

Neuroprotective Effect of Tauroursodeoxycholic Acid (TUDCA) on In Vitro and In Vivo Models of Retinal Disorders: A Systematic Review.

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a naturally produced hydrophilic bile acid that has been used for centuries in Chinese medicine. Numerous recent in vitro and in vivo studies have shown that TUDCA has neuroprotective action in various models of retinal disorders. OBJECTIVE: To systematically review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA. METHODS: A systematic review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, "TUDCA" in combination with "retina", "retinal protection", "neuroprotection" were searched. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text review. Six of them were in vitro experiments, 17 studies reported in vivo data and one study described both in vitro and in vivo data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal gangli on cell (RGC) damage, Leber's hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the in vivo studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE's risk of bias tool. Both in vitro and in vivo data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum(ES) stress, and reducing angiogenesis. CONCLUSION: This systematic review demonstrated that TUDCA has neuroprotective effect on in vivo and in vitro models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.

Mass spectrometry-based assays for assessing replicative bypass and repair of DNA alkylation in cells.

Endogenous metabolism and environmental exposure can give rise to DNA alkylation, which can elicit deleterious biological consequences. In the search for reliable and quantitative analytical methods to elucidate the impact of DNA alkylation on the flow of genetic information, mass spectrometry (MS) has attracted increasing attention, owing to its unambiguous determination of molecular mass. The MS-based assays obviate conventional colony-picking methods and Sanger sequencing procedures, and retained the high sensitivity of postlabeling methods. With the help of the CRISPR/Cas9 gene editing method, MS-based assays showed high potential in studying individual functions of repair proteins and translesion synthesis (TLS) polymerases in DNA replication. In this mini-review, we have summarized the development of MS-based competitive and replicative adduct bypass (CRAB) assays and their recent applications in assessing the impact of alkylation on DNA replication. With further development of MS instruments for high resolving power and high throughput, these assays should be generally applicable and efficient in quantitative measurement of the biological consequences and repair of other DNA lesions.

Preparation and Adsorption Performance Study of Graphene Quantum Dots@ZIF-8 Composites for Highly Efficient Removal of Volatile Organic Compounds.

Based on the large specific surface area and excellent adsorption potential of graphene quantum dots (GQDs) and zeolitic imidazolate framework-8 (ZIF-8) materials, a GQDs@ZIF-8 composite was constructed to achieve optimal matching of the microstructure and to acquire efficient adsorption of volatile organic compounds (VOCs). GQDs and ZIF-8 were synthesized and then compounded by the solution co-deposition method to obtain GQDs@ZIF-8 composites. GQDs were uniformly decorated on the surface of the ZIF-8 metal-organic framework (MOF), effectively restraining the agglomeration, improving the thermal stability of ZIF-8 and forming abundant active sites. Thus, the VOC removal percentage and adsorption capacity of the GQDs@ZIF-8 composites were significantly improved. Toluene and ethyl acetate were chosen as simulated VOC pollutants to test the adsorption performance of the composites. The results showed that, after the addition of GQDs, the adsorption property of GQDs@ZIF-8 composites for toluene and ethyl acetate was obviously improved, with maximum adsorption capacities of 552.31 mg/g and 1408.59 mg/g, respectively, and maximum removal percentages of 80.25% and 93.78%, respectively, revealing extremely high adsorption performance. Compared with raw ZIF-8, the maximum adsorption capacities of the composites for toluene and ethyl acetate were increased by 53.82 mg/g and 104.56 mg/g, respectively. The kinetics and isotherm study revealed that the adsorption processes were in accordance with the pseudo-first-order kinetic model and the Freundlich isotherm model. The thermodynamic results indicated that the adsorption process of the GQDs@ZIF-8 composites was a spontaneous, endothermic and entropy increase process. This study provides a new way to explore MOF-based adsorption materials with high adsorption capacity which have broad application prospects in VOC removal fields.

Correction: Biofunctional Janus particles promote phagocytosis of tumor cells by macrophages.

[This corrects the article DOI: 10.1039/D0SC01146K.].

Degradation of formaldehyde aqueous solution by Bi based catalyst and its activity evaluation.

Bi based catalysts have attracted continuous attention from the scientific community because of their excellent photochemical properties and wide application in photocatalytic treatment of environmental pollution. A series of Bi based catalysts with good crystallinity and high purity were prepared by calcination and hydrothermal synthesis. In the application of degrading formaldehyde aqueous solution in a mercury lamp and xenon lamp atmosphere, it was found that BiVO4 and Bi2WO6 showed excellent photochemical properties under ultraviolet and visible light. The tests of PL, UV-Vis and EIS confirmed their high activity. In the calculation based on density functional theory (DFT), through the analysis of the energy band structure, density of states (DOS) and partial wave density of states (PDOS), it is found that the d orbital of V and W elements has a great influence on the position and size of the energy band of the catalyst, which makes it have high activity and excellent electrochemical properties.

Identification of Genes Related to Cold Tolerance and Novel Genetic Markers for Molecular Breeding in Taiwan Tilapia (Oreochromis spp.) via Transcriptome Analysis.

Taiwan tilapia is one of the primary species used in aquaculture practices in Taiwan. However, as a tropical fish, it is sensitive to cold temperatures that can lead to high mortality rates during winter months. Genetic and broodstock management strategies using marker-assisted selection and breeding are the best tools currently available to improve seed varieties for tilapia species. The purpose of this study was to develop molecular markers for cold stress-related genes using digital gene expression analysis of next-generation transcriptome sequencing in Taiwan tilapia (Oreochromis spp.). We constructed and sequenced cDNA libraries from the brain, gill, liver, and muscle tissues of cold-tolerance (CT) and cold-sensitivity (CS) strains. Approximately 35,214,833,100 nucleotides of raw sequencing reads were generated, and these were assembled into 128,147 unigenes possessing a total length of 185,382,926 bp and an average length of 1446 bp. A total of 25,844 unigenes were annotated using five protein databases and Venny analysis, and 38,377 simple sequence repeats (SSRs) and 65,527 single nucleotide polymorphisms (SNPs) were identified. Furthermore, from the 38-cold tolerance-related genes that were identified using differential gene expression analysis in the four tissues, 13 microsatellites and 37 single nucleotide polymorphism markers were identified. The results of the genotype analysis revealed that the selected markers could be used for population genetics. In addition to the diversity assessment, one of the SNP markers was determined to be significantly related to cold-tolerance traits and could be used as a molecular marker to assist in the selection and verification of cold-tolerant populations. The specific genetic markers explored in this study can be used for the identification of genetic polymorphisms and cold tolerance traits in Taiwan tilapia, and they can also be used to further explore the physiological and biochemical molecular regulation pathways of fish that are involved in their tolerance to environmental temperature stress.

A polymeric nanoformulation improves the bioavailability and efficacy of sorafenib for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivo studies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.

Patellar resurfacing versus patellar nonresurfacing in primary total knee arthroplasty: A protocol for systematic review and meta analysis.

BACKGROUND: Total knee arthroplasty (TKA) is one of the most common orthopedic procedures. However, the decision to resurface the patella during a primary TKA remains controversial. Therefore, a systematic review and meta-analysis were conducted to determine whether patellar resurfacing is needed in primary total knee arthroplasty. METHODS: A systematic literature research will be conducted in 7 databases including PubMed, Embase, Cochrane Library website, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database for Chinese Technical Periodicals. The quality of studies will be assessed according to Cochrane risk of bias tool and Methodological index for non-randomized studies (MINORS) scale. The level of the evidence will be estimated by grading of recommendations assessment, development, and evaluation system. Data analysis and synthesis will be completed by the Review Manager 5.3. CONCLUSIONS: The conclusion of this study will provide clinicians performing TKA with a recommendation whether to conduct patellar resurfacing and further guide the clinical decision-making.PROSPERO registration number: CRD42019129711.

Engineering nanoparticles to tackle tumor barriers.

Engineering nanoparticles (NPs) as delivery systems of anticancer therapeutics has attracted tremendous attention in recent decades, and some nanoscale drug formulations have been approved for clinical use. However, their therapeutic efficacies are still limited by the presence of a series of biological barriers during the delivery process. Among these obstacles, tumor barriers are generally recognized as the bottleneck, because they dominate the NP extravasation from the tumor vasculature and penetration into the tumor parenchyma. Therefore, this review first discussed tumor barriers from two aspects: tumor vascular barriers and tumor stromal barriers. Pathological features of the two sets of barriers as well as their influence on the delivery efficacy were described. Then, we outlined strategies for engineering NPs to overcome these challenges: increasing extravasation through physical property optimization and tumor vascular targeting; and facilitating deep penetration through particle size manipulation, modulation of the tumor extracellular matrix, and some new mechanisms. This review will provide a critical perspective on engineering strategies for more efficient nanomedicine in oncology.

Electric field triggered release of gas from a quasi-one-dimensional hydrate in the carbon nanotube.

We systematically investigate the effects of an axial electric field on the formation and decomposition of quasi-one-dimensional nitrogen gas hydrates within a single-walled carbon nanotube (SWNT) by using molecular dynamics (MD) simulations. We find that the nitrogen hydrate in the SWNT undergoes a series of structure phase transitions with increasing electric field. Corresponding to the structure transition, the nitrogen gas releases from the carbon nanotube in the electric field range of 1 V nm-1 to 2 V nm-1. However, nitrogen molecules are trapped as guest molecules, forming a molecule wire, in the ice nanotube when the electric field is less than 1 V nm-1 or larger than 2 V nm-1. Our simulations indicate that the nanotube is an excellent tiny gas tank that can be used to trap gas molecules and control their release triggered sensitively by electric signals. The key to this phenomenon is the change in orientations of water dipoles induced by the electric field, which leads to the structural change in the hydrogen-bonding network and the change in the diffusion coefficient of the water molecules. Our findings here may help understanding the mechanism of the electrorelease of gas from hydrates confined in the nanoscale space.

Angiopep-2 conjugated nanoparticles loaded with doxorubicin for the treatment of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood-brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

Biofunctional Janus particles promote phagocytosis of tumor cells by macrophages.

Herein, a versatile strategy for the construction of biofunctional Janus particles (JPs) through the combination of Pickering emulsion and copper-free click chemistry is developed for the study of particle-mediated cell-cell interactions. A variety of biomolecules including bovine serum albumin (BSA), ferritin, transferrin (Tf), and anti-signal regulatory protein alpha antibodies (aSIRPα), etc., can be incorporated into the Janus platform in a spatially defined manner. JPs consisting of Tf and aSIRPα (Tf-SPA1-aSIRPα JPs) demonstrate a significantly improved binding affinity to either macrophages or tumor cells compared to their uniformly modified counterparts. More importantly, Tf-SPA1-aSIRPα JPs mediate more efficient phagocytosis of tumor cells by macrophages as revealed by real-time high-content confocal microscopy. This study demonstrates the potential advantages of JPs in mediating cell-cell interactions and may contribute to the emerging cancer immunotherapy.

Lactobacillus paracasei PS23 Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice.

Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain dysfunction remains unclear. To investigate the effects of Lactobacillus paracasei PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (n = 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut⁻brain axis communication.