Polydopamine-Coated Polymer Nanofibers for In Situ Protein Loading and Controlled Release.

Nanofibrous polymeric materials, combined with protein therapeutics, play a significant role in biomedical and pharmaceutical applications. However, the upload of proteins into nanofibers with a high yield and controlled release has been a challenging issue. Here, we report the in situ loading of a model protein (bovine serum albumin) into hydrophilic poly(vinyl alcohol) nanofibers via ice-templating, with a 100% protein drug loading efficiency. These protein-loaded nanofibers were further coated by polydopamine in order to improve the nanofiber stability and achieve a controlled protein release. The mass ratio between poly(vinyl alcohol) and bovine serum albumin influenced the percentage of proteins in composite nanofibers and fiber morphology. More particles and less nanofibers were formed with an increasing percentage of bovine serum albumin. By varying the coating conditions, it was possible to produce a uniform polydopamine coating with tunable thickness, which acted as an additional barrier to reduce burst release and achieve a more sustained release profile.

Challenging pitfalls in frozen section pathology: a case of mandible ghost cell odontogenic carcinoma and the literature review.

BACKGROUND: Ghost cell odontogenic carcinoma (GCOC) is a rare malignancy characterized by the presence of ghost cells, preferably in the maxilla. Only slightly more than 50 case reports of GCOC have been documented to date. Due to the rarity of this tumor and its nonspecific clinical criteria, there is a heightened risk of misdiagnosis in clinical examination, imaging findings, and pathology interpretation. CASE PRESENTATION: A 50-year-old male patient presented to the hospital due to experiencing pain in his lower front teeth while eating for the past 2 months. Upon examination, a red, hard, painless mass was found in his left lower jaw, measuring approximately 4.0 cm × 3.5 cm. Based on the malignant histological morphology of the tumor and the abundant red-stained keratinized material, the preoperative frozen section pathology misdiagnosed it as squamous cell carcinoma (SCC). The surgical resection specimen pathology via paraffin section revealed that the tumor was characterized by round-like epithelial islands within the fibrous interstitium, accompanied by a large number of ghost cells and some dysplastic dentin with infiltrative growth. The malignant components displayed marked heterogeneity and mitotic activity. Additionally, a calcified cystic tumor component of odontogenic origin was observed. Hemorrhage, necrosis, and calcifications were present, with a foreign body reaction around ghost cells. Immunoreactivity for ß-catenin showed strong nuclear positivity in tumor cells, while immunostaining was completely negative for p53. The Ki67 proliferation index was approximately 30-40%. The tumor cells exhibited diffuse CK5/6, p63, and p40 immunoreactivity, with varying immunopositivity for EMA. Furthermore, no BRAFV600E mutation was identified by ARMS-PCR. The final pathology confirmed that the tumor was a mandible GCOC. CONCLUSION: We have reported and summarized for the first time the specific manifestations of GCOC in frozen section pathology and possible pitfalls in misdiagnosis. We also reviewed and summarized the etiology, pathological features, molecular characteristics, differential diagnosis, imaging features, and current main treatment options for GCOC. Due to its rarity, the diagnosis and treatment of this disease still face certain challenges. A correct understanding of the pathological morphology of GCOC, distinguishing the ghost cells and the secondary stromal reaction around them, is crucial for reducing misdiagnosis rates.

Modification of nanodiamonds for fluorescence bioimaging.

Non-invasive bioimaging is essential in enhancing pre-clinical diagnosis and therapy. Developing efficient imaging probes with high stability, low toxicity, and the potential of offering high resolution images is a very important aspect of developing non-invasive bioimaging techniques. Fluorescent nanodiamonds, which are produced by high energy beam irradiation and high temperature/pressure treatment, have been extensively investigated. In this study, we report the chemical modification of common nanodiamonds (prepared by detonation and high-pressure high-temperature milling) using a stable fluorophore (perylene diimide derivative) via carbodiimide coupling. The resulting nanodiamonds show good biocompatibility, cellular uptake and fluorescent imaging potential with mesenchymal stromal cells. This method provides an efficient alternative approach to the preparation and the use of fluorescent nanodiamonds for bioimaging, with the potential benefit of chemically adjusting the structure of perylene diimide for optimized emission/absorbance wavelength.

An MRI brain tumor segmentation method based on improved U-Net.

In order to improve the segmentation effect of brain tumor images and address the issue of feature information loss during convolutional neural network (CNN) training, we present an MRI brain tumor segmentation method that leverages an enhanced U-Net architecture. First, the ResNet50 network was used as the backbone network of the improved U-Net, the deeper CNN can improve the feature extraction effect. Next, the Residual Module was enhanced by incorporating the Convolutional Block Attention Module (CBAM). To increase characterization capabilities, focus on important features and suppress unnecessary features. Finally, the cross-entropy loss function and the Dice similarity coefficient are mixed to compose the loss function of the network. To solve the class unbalance problem of the data and enhance the tumor area segmentation outcome. The method's segmentation performance was evaluated using the test set. In this test set, the enhanced U-Net achieved an average Intersection over Union (IoU) of 86.64% and a Dice evaluation score of 87.47%. These values were 3.13% and 2.06% higher, respectively, compared to the original U-Net and R-Unet models. Consequently, the proposed enhanced U-Net in this study significantly improves the brain tumor segmentation efficacy, offering valuable technical support for MRI diagnosis and treatment.

Mapping enhancer and chromatin accessibility landscapes charts the regulatory network of Alzheimer's disease.

BACKGROUND: Enhancers are regulatory elements that target and modulate gene expression and play a role in human health and disease. However, the roles of enhancer regulatory circuit abnormalities driven by epigenetic alterations in Alzheimer's disease (AD) are unclear. METHODS: In this study, a multiomic integrative analysis was performed to map enhancer and chromatin accessibility landscapes and identify regulatory network abnormalities in AD. We identified differentially methylated enhancers and constructed regulatory networks across brain regions using AD brain tissue samples. Through the integration of snATAC-seq and snRNA-seq datasets, we mapped enhancers with DNA methylation alterations (DMA) and chromatin accessibility landscapes. Core regulatory triplets that contributed to AD neuropathology in specific cell types were further prioritized. RESULTS: We revealed widespread DNA methylation alterations (DMA) in the enhancers of AD patients across different brain regions. In addition, the genome-wide transcription factor (TF) binding profiles showed that enhancers with DMA are pervasively regulated by TFs. The TF-enhancer-gene regulatory network analysis identified core regulatory triplets that are associated with brain and immune cell proportions and play important roles in AD pathogenesis. Enhancer regulatory circuits with DMA exhibited distinct chromatin accessibility patterns, which were further characterized at single-cell resolutions. CONCLUSIONS: Our study comprehensively investigated DNA methylation-mediated regulatory circuit abnormalities and provided novel insights into the potential pathogenesis of AD.

Efficacy and mechanism of Wuzi Yanzong pill on the prevention and treatment of EAE.

Objective: Studies have shown that Wuzi Yanzong Pill (WYP) can be used to treat neurological diseases, but its mechanisms for multiple sclerosis (MS) remain unclear. This study aims to determine the effect of WYP on MS in an animal model of experimental autoimmune encephalomyelitis (EAE), and explore its mechanism. To provide theoretical basis for the clinical treatment of MS with WYP. Methods: C57BL/6 female mice were randomly divided into Blank control, EAE control, low dose WYP, medium dose WYP, and high dose WYP groups. One week before model generation, the mice were gavaged with saline (50 mL/kg/d) in Blank control and EAE control groups. The treatment groups was gavaged with different doses of WYP solution (4, 8, or 16 g/kg/d respectively) Clinical scores were recorded daily. Sample collection was conducted on the 14th and 28th days, respectively The expressions of IL-10, IL-17, IL-12, TNF-α and IFN-γ in spleen were detected by ELISA. The expressions of ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, CCR2 in spleen, brain and spinal cord were detected by Western Blot. The types of macrophages and the contents of intracellular IL-10 and IL-12 were detected by Flow Cytometry. The contents of TNF-α and TLR4 mRNA in the spleen were detected by RT-PCR. Results: WYP treatment improved the clinical score of EAE mice in a significant dose-dependent manner, with the WYP high-dose group showed the most significant improvement in clinical score. Compared with the EAE control group, WYP high dose group had significantly lower levels of IL-17, IFN-γ, ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, and CCR2 as well as TNF-α and TLR4 mRNA, but increased the number of M2 macrophages and IL-10. Conclusion: WYP treatment relieves clinical symptoms in EAE mice, which may be related to regulate inflammatory pathway and inhibiting expressions of inflammatory cytokines.

Aptamer modified Zr-based porphyrinic nanoscale metal-organic frameworks for active-targeted chemo-photodynamic therapy of tumors.

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.

Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. METHODS: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. RESULTS: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01). CONCLUSIONS: WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

Neuroprotective effect of hyperoside in MPP+/MPTP -induced dopaminergic neurodegeneration.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100 µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25 mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H2O2, and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP+/MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP+- and MPTP-induced injuries, which did not rely on the Akt pathway.

Preparation of PLGA-Coated Porous Silica Nanofibers for Drug Release.

Fibrous materials have unique applications in drug release and biomedical fields. This study reports on the preparation of porous silica nanofibers, using organic nanofibers as templates, and their use for drug release. Different from the commonly used electrospinning method, the organic nanofibers are produced via a self-assembly approach between melamine and benzene-1,3,5-tricarboxylic acid. Silica is then coated on the organic nanofibers via homogenization in a silica sol, a freeze-drying process, and then a sol-gel process. In order to regulate the surface area and mesopore volume of silica nanofibers, cetyltrimethyl ammonium bromide at different concentrations is used as template in the sol-gel process. With the removal of organic nanofibers and the surfactant by calcination, porous silica nanofibers are generated and then assessed as a scaffold for controlled drug release with ketoprofen as a model drug. Poly (D, L-lactide-co-glycolide) is coated on the silica nanofibers to achieve slow burst release and prolonged cumulative release of 25 days. This study demonstrates an effective method of preparing hollow silica nanofibers and the use of such nanofibers for long-term release with high drug loading.

Evaluation of Cytotoxicity and Bioimaging of Nitrogen-Vacancy Nanodiamonds.

Nanodiamonds, due to their chemical inertness and biocompatibility, have found extensive uses in drug delivery and biomedical applications. Fluorescent nanodiamonds with fluorescent properties generated by nitrogen-vacancy defects have been intensively investigated for bioimaging, due to their high quantum yield and high photobleaching stability. In addition, the surface properties and particle size of nanodiamonds have significant impacts on cellular uptake and imaging quality. In this study, nitrogen-vacancy nanodiamonds with different particle sizes (40 nm and 90 nm) have been physicochemically characterised and investigated for their cytotoxicity and potential in fluorescence imaging. The nanodiamonds (with concentrations up to 100 µg/mL) showed cell viability >70% with mesenchymal stromal cells. The number of nanodiamonds was observed to have a larger impact on cell viability than the mass of nanodiamonds. Larger nanodiamonds (90 nm) exhibited a lower level of cytotoxicity, higher cellular uptake and fluorescence intensity. The results indicate the potential of using fluorescent nanodiamonds as a nanoprobe for effective bioimaging and cell tracking.

Hydroxysafflor Yellow A Exerts Neuroprotective Effects via HIF-1α/BNIP3 Pathway to Activate Neuronal Autophagy after OGD/R.

In the process of ischemic stroke (IS), cellular macroautophagy/autophagy and apoptosis play a vital role in neuroprotection against it. Therefore, regulating their balance is a potential therapeutic strategy. It has been proved that hydroxysafflor yellow A (HSYA) has anti-inflammatory and antioxidant effects, which can both protect neurons. By exploring bioinformatics combined with network pharmacology, we found that HIF1A and CASP3, key factors regulating autophagy and apoptosis, may be important targets of HSYA for neuroprotection in an oxygen glucose deprivation and reperfusion (OGD/R) model. In this study, we explored a possible new mechanism of HSYA neuroprotection in the OGD/R model. The results showed that OGD/R increased the expression of HIF1A and CASP3 in SH-SY5Y cells and induced autophagy and apoptosis, while HSYA intervention further promoted the expression of HIF1A and inhibited the level of CASP3, accompanied by an increase in autophagy and a decrease in apoptosis in SH-SY5Y cells. The inhibition of HIF1A diminished the activation of autophagy induced with HSYA, while the inhibition of autophagy increased cell apoptosis and blocked the neuroprotective effect of HSYA, suggesting that the neuroprotective effect of HSYA should be mediated by activating the HIF1A/BNIP3 signaling pathway to induce autophagy. These results demonstrate that HSYA may be a promising agent for treating IS.

Network Architecture for Optimizing Deep Deterministic Policy Gradient Algorithms.

The traditional Deep Deterministic Policy Gradient (DDPG) algorithm has been widely used in continuous action spaces, but it still suffers from the problems of easily falling into local optima and large error fluctuations. Aiming at these deficiencies, this paper proposes a dual-actor-dual-critic DDPG algorithm (DN-DDPG). First, on the basis of the original actor-critic network architecture of the algorithm, a critic network is added to assist the training, and the smallest Q value of the two critic networks is taken as the estimated value of the action in each update. Reduce the probability of local optimal phenomenon; then, introduce the idea of dual-actor network to alleviate the underestimation of value generated by dual-evaluator network, and select the action with the greatest value in the two-actor networks to update to stabilize the training of the algorithm process. Finally, the improved method is validated on four continuous action tasks provided by MuJoCo, and the results show that the improved method can reduce the fluctuation range of error and improve the cumulative return compared with the classical algorithm.

Silica Microspheres-in-Pores Composite Monoliths with Fluorescence and Potential for Water Remediation.

Water pollution is a severe worldwide issue. Constructing advanced porous composite materials has been an efficient route to water remediation via adsorption. In this study, a unique microspheres-in-pores monolithic structure was fabricated. An emulsion-templated polymer monolith was first prepared and silica microspheres were subsequently formed in the porous polymer. A silica precursor was modified with a fluorescent dye and co-condensed with other precursors to fabricate porous composites with fluorescent properties, which were enhanced by the presence of Ag nanoparticles in the polymer matrix. This unique material showed good promise in water remediation by removing organic dyes and heavy metal ions from wastewater via a flowing filter or monolithic column separation.

Fundamentals and Design-Led Synthesis of Emulsion-Templated Porous Materials for Environmental Applications.

Emulsion templating is at the forefront of producing a wide array of porous materials that offers interconnected porous structure, easy permeability, homogeneous flow-through, high diffusion rates, convective mass transfer, and direct accessibility to interact with atoms/ions/molecules throughout the exterior and interior of the bulk. These interesting features together with easily available ingredients, facile preparation methods, flexible pore-size tuning protocols, controlled surface modification strategies, good physicochemical and dimensional stability, lightweight, convenient processing and subsequent recovery, superior pollutants remediation/monitoring performance, and decent recyclability underscore the benchmark potential of the emulsion-templated porous materials in large-scale practical environmental applications. To this end, many research breakthroughs in emulsion templating technique witnessed by the recent achievements have been widely unfolded and currently being extensively explored to address many of the environmental challenges. Taking into account the burgeoning progress of the emulsion-templated porous materials in the environmental field, this review article provides a conceptual overview of emulsions and emulsion templating technique, sums up the general procedures to design and fabricate many state-of-the-art emulsion-templated porous materials, and presents a critical overview of their marked momentum in adsorption, separation, disinfection, catalysis/degradation, capture, and sensing of the inorganic, organic and biological contaminants in water and air.

Hyperbranched Polyethylenimine-Tethered Multiple Emulsion-Templated Hierarchically Macroporous Poly(acrylic acid)-Al2O3 Nanocomposite Beads for Water Purification.

Emulsion template-guided strategy has been used to produce porous architectures with exquisite structure, tailored morphology, and exclusive features for ubiquitous applications. Notwithstanding, the practical water remediation is often marred by their transport-limited behavior and fragility. To circumvent these conundrums, we prepared hierarchically porous poly(acrylic acid)-alumina nanocomposite beads by solidifying the droplets of emulsions jointly stabilized by the organic surfactants and alumina nanoparticles. By virtue of their positive charge, the alumina nanoparticles got entrapped within the poly(acrylic acid) scaffolds that excluded the risk of secondary contamination typically observed with conventional nanocomposites. Being amenable to surface modification, the carboxyl moieties of the beaded polymer were further exploited to covalently tether branched polyethylenimine throughout the exterior and interior surface of the porous matrix via a grafting-to approach. The macropores expedite an active fluid flow and easier adsorbate transport throughout the functionalized nanocomposites whose overall higher density of positive charge over a certain pH range electrostatically attracts and effectively adsorbs the negatively charged Cr(VI) complexes and anionic congo red ions/molecules from water. This proof-of-concept synthetic approach and postsynthetic modification offer an improved mechanical robustness to these macrosized multifunctional nanocomposite beads for their easier processing, thereby paving the way for the point-of-use water purification technology development.

Refinement of pore size at sub-angstrom precision in robust metal-organic frameworks for separation of xylenes.

The demand for xylenes is projected to increase over the coming decades. The separation of xylene isomers, particularly p- and m-xylenes, is vital for the production of numerous polymers and materials. However, current state-of-the-art separation is based upon fractional crystallisation at 220 K which is highly energy intensive. Here, we report the discrimination of xylene isomers via refinement of the pore size in a series of porous metal-organic frameworks, MFM-300, at sub-angstrom precision leading to the optimal kinetic separation of all three xylene isomers at room temperature. The exceptional performance of MFM-300 for xylene separation is confirmed by dynamic ternary breakthrough experiments. In-depth structural and vibrational investigations using synchrotron X-ray diffraction and terahertz spectroscopy define the underlying host-guest interactions that give rise to the observed selectivity (p-xylene < o-xylene < m-xylene) and separation factors of 4.6-18 for p- and m-xylenes.

Ice- and MOF-templated porous carbonaceous monoliths for adsorptive removal of dyes in water with easy recycling.

Various nanoporous particles, nanofibers have been employed for adsorptive removal of dyes from wastewater. However, these nanomaterials are difficult in separation from solution, generally by centrifugation or filtration. These processes are tedious and will limit the upscale applications. Herein, a hierarchically porous carbon monolith has been fabricated on grounds of ice and metal organic framework (MOF) templating method. The prepared carbonaceous monolith exhibited abundant ice-templated macropores, MOF-templated micropores and mesopores, and a high BET (Brunauer-Emmett-Teller) special surface area (530 m2 g-1). The monolith achieved an MB (methylene blue) adsorption capacity of 95.82 mg g-1 (10 mg adsorbent/5 mL aqueous dye solution) and a theoretic maximum value of 179.86 mg g-1 by the Langmuir model. Compared with MB, the adsorption capacity for MO (methyl orange) was lower. Several adsorption kinetics and isotherms models were used for analysis of adsorptive data, and the results demonstrated the adsorption of MB and MO on the porous carbon monolith is a spontaneous endothermic physisorption process, which was mainly controlled by electrostatic reaction. Importantly, the monolith could be easily picked up using tweezers and used for recycling tests. After four cycles, the 94% of the initial adsorption capacity for MB can be retained.

Prognostic Value of Programmed Cell Death 1 Ligand-1 in Patients With Bone and Soft Tissue Sarcomas: A Systemic and Comprehensive Meta-Analysis Based on 3,680 Patients.

Background: Programmed cell death 1 ligand-1 (PD-L1) is an immune checkpoint molecule that acts to protect cancer cells from immune surveillance and is considered as a prognostic biomarker in several cancers, but the prognostic value of PD-L1 in bone and soft tissue sarcomas remains inconclusive. In the present meta-analysis, the clinicopathological and prognostic value of PD-L1 in sarcomas was evaluated. Method: We performed a systemic and comprehensive meta-analysis by searching the PubMed, Medline, Cochrane Library, EMBASE, and Web of Science databases up to October 31, 2019. Eligible articles were incorporated, and pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were used to estimate the outcomes. Results: Thirty-six articles containing 39 independent studies with 3,680 bone and soft tissue sarcoma patients were included in our meta-analysis. The pooled results showed that PD-L1 overexpression could predict poor overall survival (HR 1.45, 95% CI 1.11-1.90, P < 0.01), metastasis-free survival (HR 1.58, 95% CI 1.14-2.19, P < 0.01), and event-free survival (HR 2.82, 95% CI 1.69-4.71, P < 0.01) in sarcomas. Furthermore, PD-L1 overexpression was correlated with a higher rate of tumor metastasis (OR 2.95, 95% CI 1.32-6.60, P < 0.01), a more advanced tumor grade (OR 3.63, 95% CI 2.55-5.16, P < 0.01), and more T lymphocyte infiltration (OR 5.55, 95% CI 2.86-10.76, P < 0.01). No obvious publication bias was observed, and the sensitivity analysis showed that our results were robust. Conclusion: The results of our meta-analysis indicate that high PD-L1 expression might serve as a valuable and predictive biomarker for adverse clinicopathological features and poor prognosis in patients with sarcoma.

Perylene Diimide Nanoprobes for In Vivo Tracking of Mesenchymal Stromal Cells Using Photoacoustic Imaging.

Noninvasive bioimaging techniques are critical for assessing the biodistribution of cellular therapies longitudinally. Among them, photoacoustic imaging (PAI) can generate high-resolution images with a tissue penetration depth of ∼4 cm. However, it is essential and still highly challenging to develop stable and efficient near-infrared (NIR) probes with low toxicity for PAI. We report here the preparation and use of perylene diimide derivative (PDI) with NIR absorbance (around 700 nm) as nanoprobes for tracking mesenchymal stromal cells (MSCs) in mice. Employing an in-house synthesized star hyperbranched polymer as a stabilizer is the key to the formation of stable PDI nanoparticles with low toxicity and high uptake by the MSCs. The PDI nanoparticles remain within the MSCs as demonstrated by in vitro and in vivo assessments. The PDI-labeled MSCs injected subcutaneously on the flanks of the mice are clearly visualized with PAI up to 11 days postadministration. Furthermore, bioluminescence imaging of PDI-labeled luciferase-expressing MSCs confirms that the administered cells remain viable for the duration of the experiment. These PDI nanoprobes thus have good potential for tracking administered cells in vivo using PAI.