Organic-Inorganic Rare-Earth Double Perovskite Ferroelectric with Large Piezoelectric Response and Ferroelasticity for Flexible Composite Energy Harvesters.

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

Ferritin-Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy.

Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug-loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin-based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin-loaded human ferritin (Dox@HFn) and oxidized dextran (Dex-CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH-sensitive Schiff-base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti-programmed death-1 antibody (αPD-1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti-tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti-CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy.

Virus-Inspired Glucose and Polydopamine (GPDA)-Coating as an Effective Strategy for the Construction of Brain Delivery Platforms.

The ability of drugs to cross the blood-brain barrier (BBB) is crucial for treating central nervous system (CNS) disorders. Inspired by natural viruses, here we report a glucose and polydopamine (GPDA) coating method for the construction of delivery platforms for efficient BBB crossing. Such platforms are composed of nanoparticles (NPs) as the inner core and surface functionalized with glucose-poly(ethylene glycol) (Glu-PEG) and polydopamine (PDA) coating. Glu-PEG provides selective targeting of the NPs to brain capillary endothelial cells (BCECs), while PDA enhances the transcytosis of the NPs. This strategy is applicable to gold NPs (AuNPs), silica, and polymeric NPs, which achieves as high as 1.87% of the injected dose/g of brain in healthy brain tissues. In addition, the GPDA coating manages to deliver NPs into the tumor tissue in the orthotopic glioblastoma model. Our study may provide a universal strategy for the construction of delivery platforms for efficient BBB crossing and brain drug delivery.

[Qirong Tablets inhibits apoptosis of ovarian granulosa cells via PI3K/Akt/ HIF-1 signaling pathway].

This study aims to observe the effect and explore the mechanism of Qirong Tablets in the treatment of premature ovarian insufficiency(POI) in mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly divided into normal group, model group, positive control group, Qirong Tablets low-, medium-and high-dose group. The normal group was intraperitoneally injected with the same amount of normal saline, and the other groups were intraperitoneally injected with cyclophosphamide 120 mg·kg~(-1)·d~(-1) once to establish a POI animal model. After the model was successfully established, the low-, medium-and high-dose groups of Qirong Tablets were administered orally with 0.6, 1.2, 2.4 mg·kg~(-1)·d~(-1) respectively. The positive control group was given 0.22 mg·kg~(-1)·d~(-1) Clementine Tablets by intragastric administration, and the normal group and model group were given intragastric administration with the same amount of normal saline, and the treatment was 28 d as a course of treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with the normal group, the modeling of POI caused loose or destroyed ovarian tissue with vacuolar structures, edema and fibrosis in the ovarian interstitium, disordered or loose arrangement of granulosa cells, and reduced normal follicles. Compared with the model group, drug interventions restored the ovarian tissue and follicles at all the development stages and reduced atretic follicles. Compared with the normal group, the modeling of POI lowered the serum level of E_2 and AMH(P<0.01), and elevated the level of FSH and LH(P<0.01). Compared with the model group, high-dose Qirong Tablets elevated the levels of E_2 and AMH(P<0.05), and lowered the levels of FSH and LH(P<0.05). Compared with the normal group, the modeling of POI up-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.01). Compared with the model group, low-, medium-, and high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.05). In conclusion, Qirong Tablets can up-regulate the expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, thereby delaying ovarian aging, improving reproductive axis function, and strengthening ovarian reserve capacity, which may be associated with the inhibition of PI3K/Akt/HIF-1 pathway.

Manganese-Based Immunostimulatory Metal-Organic Framework Activates the cGAS-STING Pathway for Cancer Metalloimmunotherapy.

Metal-organic frameworks (MOFs) show tremendous promise for drug delivery due to their structural and functional versatility. However, MOFs are usually used as biologically inert carriers in most cases. The creation of intrinsically immunostimulatory MOFs remains challenging. In this study, a facile and green synthesis method is proposed for the preparation of a manganese ion (Mn2+)-based immunostimulatory MOF (ISAMn-MOF) for cancer metalloimmunotherapy. ISAMn-MOF significantly facilitates the activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) related genes and signaling pathways in bone-marrow-derived dendritic cells (BMDCs). BMDCs treated with ISAMn-MOF secrete 4-fold higher type I interferon and 2- to 16-fold higher proinflammatory cytokines than those treated with equivalent MnCl2. ISAMn-MOF alone or its combination with immune checkpoint antibodies significantly suppresses tumor growth and metastasis and prolongs mouse survival. Mechanistic studies indicate that ISAMn-MOF treatment facilitates the infiltration of stimulatory immune cells in tumors and lymphoid organs. This study provides insight into the design of bioactive MOFs for improved cancer metalloimmunotherapy.

Nanoparticle-Mediated CD47-SIRPα Blockade and Calreticulin Exposure for Improved Cancer Chemo-Immunotherapy.

Enabling macrophages to phagocytose tumor cells holds great potential for cancer therapy but suffers from tremendous challenges because the tumor cells upregulate antiphagocytosis molecules (such as CD47) on their surface. The blockade of CD47 alone is insufficient to stimulate tumor cell phagocytosis in solid tumors due to the lack of "eat me" signals. Herein, a degradable mesoporous silica nanoparticle (MSN) is reported to simultaneously deliver anti-CD47 antibodies (aCD47) and doxorubicin (DOX) for cancer chemo-immunotherapy. The codelivery nanocarrier aCD47-DMSN was constructed by accommodating DOX within the mesoporous cavity, while adsorbing aCD47 on the surface of MSN. aCD47 blocks the CD47-SIRPα axis to disable the "don't eat me" signal, while DOX induces immunogenic tumor cell death (ICD) for calreticulin exposure as an "eat me" signal. This design facilitated the phagocytosis of tumor cells by macrophages, which enhanced antigen cross-presentation and elicited efficient T cell-mediated immune response. In 4T1 and B16F10 murine tumor models, aCD47-DMSN generated a strong antitumor effect after intravenous injection by increasing tumor-infiltration of CD8+ T cells. Taken together, this study offers a nanoplatform to modulate the phagocytosis of macrophages for efficacious cancer chemo-immunotherapy.

Comparative study of optical coherence tomograph and histological images of eustachian tube nasopharyngeal region and adjacent structures in vivo and ex-vivo miniature pigs.

OBJECTIVES: Optical Coherence Tomograph (OCT) imaging technology can be used to examine, in vivo, the human ET. At present, it is impossible to achieve the OCT scanning vivo and ex vivo in the same individual human body, or study the consistency between OCT images and histological images of the eustachian tube nasopharyngeal region and adjacent structures. The aim of this study was to determine the consistency between OCT images and histological sections in vivo and ex vivo in miniature pigs. METHODS: OCT imaging was performed on five adult miniature pigs in vivo and ex vivo. The images of the eustachian tube OCT (ET-OCT), nasopharynx OCT (NP-OCT) and histological cross sections were further studied. RESULTS: All five miniature pigs achieved the OCT scan successfully, acquiring ET-OCT and NP-OCT images in vivo and ex vivo on both sides. The acquired ET OCT images closely matched the histological images, revealing details of the cartilage, submucosa, glands, and mucosa. The lower segment of the ET wall mucosa had an abundance of glands and submucosal tissues, with more low-signal areas appearing in the ex vivo images. The NP-OCT images of the nasopharynx matched the details of the mucosa and submucosal tissues. The ex-vivo OCT images showed thicker mucosa and more scattered slightly lower signal areas compared to the vivo OCT images. CONCLUSIONS: ET-OCT images and NP-OCT images matched the histological structure of eustachian tube nasopharyngeal region structures in miniature pigs both in vivo and ex vivo. OCT images may be sensitive to changes in edema and ischemia status. There is a great potential for morphological assessment of inflammation, edema, injure, mucus gland status.

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

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

Autoimmune thyroiditis in patients with sudden sensorineural hearing loss.

Objective: This study aims to evaluate the association between autoimmune thyroiditis and Sudden Sensorineural Hearing Loss (SSNHL). Methods: Hundred and five patients with SSNHL were enrolled. Audiometric tests, serum thyroid autoantibodies (TPOAb, TgAb) were studied. Based on the thyroid autoantibody results, patients were divided into two groups: thyroid autoantibody-positive and negative. The relationship between thyroid autoimmunity and audiological characteristics was analyzed. Results: Twenty-six patients (24.8%) of the SSNHL had thyroid autoantibody elevated. The pure tone average (PTA) of patients with and without thyroid autoantibody is 60 ± 38.51 and 54.99 ± 33.87 dBHL, respectively. The PTA was significantly improved in both groups after treatment (p < 0.001), but the hearing gains were similar in both groups (p = 0.205). Hearing loss of 2000-8000 Hz was worse than 125-1000 Hz among thyroid autoantibody-positive patients (p < 0.05), but the hearing improvement of both groups have no significant difference. The hearing improvement of 125-1000 Hz is significantly better than 2000-8000 Hz among patients with thyroid autoantibody negative (p < 0.05). Conclusions: We speculate that a potential association between thyroid autoimmunity and SSNHL. Thyroid autoimmunity may be a pathogenesis factor of SSNHL and associated with more severe hearing loss of high-frequency hearing.

Laser-assisted hatching zona thinning does not improve the pregnancy outcomes of poor-quality blastocysts in frozen-thawed embryo transfer cycle: a retrospective cohort study.

It had been suggested, after facilitating the hatching process, improved pregnancy outcomes could be attained in embryos with thick and hard zona. This study aimed to determine the effect of zona thinning on pregnancy outcomes in poor-quality frozen-thawed blastocysts. This retrospective study included 230 women (≤ 40 years) who underwent frozen embryo transfer of poor-quality blastocysts (scored < 3BB). In total, 105 patients were in the assisted hatching group in which the zona was thinned by laser before transfer and 125 patients were in the control group in which the blastocysts were non-manipulated. Patients' demographics, cycle characteristics, and pregnancy outcomes were compared between the assisted hatching group and the control group. Further, regression analysis was applied to test the correlation between assisted hatching and live birth. All parameters in the patients' demographic characteristics and the cycle's characteristics were not significantly different between two groups. As for pregnancy outcomes, the second trimester pregnancy loss was significantly higher in the assisted hatching group (P = 0.035). Other pregnancy outcomes, including implantation rate, clinical pregnancy rate, biochemical miscarriage rate, the first trimester pregnancy loss, ongoing pregnancy rate, and live birth rate were comparable between two groups. The logistic regression analysis demonstrated no association between live birth and assisted hatching (univariate, OR = 0.787, P > 0.05; multivariate, OR = 0.652, P > 0.05), and the area under the receiver operating characteristic curve of the regression model was almost 0.7. It suggested that zona thinning may not be supposed to perform on poor-quality, frozen-thawed blastocysts. The indications of assisted hatching were still needed to further investigate.

What is optimal timing of warming for transferring vitrified cleavage stage of day 3 slow-growing embryos? A cohort retrospective study.

PURPOSE: To evaluate optimal warming time, the early warming or the routine warming time, for transferring vitrified-warmed and cultured overnight cleavage stage of the slow-growing embryos on day 3 in frozen embryo transfer (FET) cycle. METHODS: This was a retrospective cohort study from January 2017 to July 2018. A total of 705 FET patients aged < 40 years were included and 1486 embryos were formed, of which 1366 embryos were eventually transferred. RESULTS: For slow-growing embryos, the clinical pregnancy rate of early warming group [152/468 (32.5%)] was significantly higher than that of routine warming group (55/235 (23.4%)) [OR 1.39 (CI 1.06-1.81), p = 0.01], while there was no statistically significant difference in pregnancy loss in early warming group [39/170 (22.9%)] versus in routine warming group [16/62 (25.8%)] [OR 0.89 (CI 0.53-1.47), p = 0.65]. CONCLUSION: For slow-growing embryos, higher pregnancy outcomes were shown in early warming strategy as compared to the routine warming, which suggested that the improvement of endometrium-embryo synchronism may correct the time difference brought by the slow-growing embryos.

Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome.

Background: rs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined. Methods: Three-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns. Results: Generally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice. Conclusion: Overall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

A Tumor-Penetrating Nanomedicine Improves the Chemoimmunotherapy of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a low survival rate. The therapeutic effect of chemotherapy and immunotherapy for PDAC is disappointing due to the presence of dense tumor stroma and immunosuppressive cells in the tumor microenvironment (TME). Herein, a tumor-penetrating nanoparticle is reported to modulate the deep microenvironment of PDAC for improved chemoimmunotherapy. The tumor pH-sensitive polymer is synthesized by conjugating N,N-dipentylethyl moieties and monomethoxylpoly(ethylene glycol) onto PAMAM dendrimer, into whose cavity a hydrophobic gemcitabine (Gem) prodrug is accommodated. They self-assemble into nanoparticles (denoted as SPN@Pro-Gem) with the size around 120 nm at neutral pH, but switch into small particles (≈8 nm) at tumor site to facilitate deep delivery of Gem into the tumor parenchyma. In addition to killing cancer cells that resided deeply in the tumor tissue, SPN@Pro-Gem could modulate the TME by reducing the abundance of tumor-associated macrophages and myeloid-derived suppressor cells as well as upregulating the expression level of PD-L1 of tumor cells. This collectively facilitates the infiltration of cytotoxic T cells into the tumors and renders checkpoint inhibitors more effective in previously unresponsive PDAC models. This study reveals a promising strategy for improving the chemoimmunotherapy of pancreatic cancer.

LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma.

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC (P=0.040) and HNSCC (P=0.044), especially in HPV 16 integrated CC (P=0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC (P=0.013) and HNSCC (P=0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC (P=1.76e-67) and HNSCC (P<10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status (P<10e-10), higher mutation count (P<10e-10), higher fraction genome altered value (P=2.078e-4), higher aneuploidy score (P=3.362e-4), and earlier started the smoking year (P=2.572e-4), which were associated with shorter overall survival (P=0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC.

Investigations on the potential of optical coherence tomography as an imaging tool for eustachian tube.

The purpose of this study was to explore the feasibility of eustachian tube optical coherence tomography (ET-OCT) for imaging the pharyngeal region of the eustachian tube (ET). Ten subjects with ear complaints underwent ET-OCT guided by nasal endoscopy, and ET-OCT examination was performed on both sides of each subject's ETs. The process and resulting images were analysed. Ten subjects ranging from 21 to 73 years old (45 ± 14.77) were enrolled in this study. Eighteen ET-OCT imaging examinations were completed. The mean duration of each examination was 2.80 ± 1.62 min (ranging from 2 to 7 min). There were no adverse events or complications. In some subjects, the ET-OCT images clearly presented the microstructures of the ET wall, including the lumen, mucosa, submucosa, cartilage and plica. However, in some subjects, it showed different characteristics, such as an unclear hierarchy and secretions in the lumen. ET-OCT may help to distinguish the structural composition of the ET and elucidate related pathophysiological mechanisms. It is a valuable imaging tool suited for the ET, with potential diagnostic value in determining the morphology of the lumen, intraluminal mucosa and submucosal tissue in the pharyngeal region of the ET.

Nanoparticle-Enabled Dual Modulation of Phagocytic Signals to Improve Macrophage-Mediated Cancer Immunotherapy.

Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti-phagocytic signals (e.g., CD47 molecules) on their surface. To promote phagocytosis of macrophages, a pro-phagocytic nanoparticle (SNPACALR&aCD47 ) that concurrently carries CD47 antibody (aCD47) and a pro-phagocytic molecule calreticulin (CALR) is constructed to simultaneously modulate the phagocytic signals of macrophages. SNPACALR&aCD47 can achieve targeted delivery to tumor cells by specifically binding to the cell-surface CD47 and block the CD47-SIRPα pathway to inhibit the "don't eat me" signal. Tumor cell-targeted delivery increases the exposure of recombinant CALR on the cell surface and stimulates an "eat me" signal. Simultaneous modulation of the two signals enhances the phagocytosis of 4T1 tumor cells by macrophages, which leads to significantly improved anti-tumor efficacy in vivo. The findings demonstrate that the concurrent blockade of anti-phagocytic signals and activation of pro-phagocytic signals can be effective in macrophage-mediated cancer immunotherapy.

Repeated Herbal Acupoint Sticking Relieved the Recurrence of Allergic Asthma by Regulating the Th1/Th2 Cell Balance in the Peripheral Blood.

Allergic asthma is an inflammatory disease involving the Th1/Th2 cell imbalance in the peripheral blood. Repeated herbal acupoint sticking (RHAS) has been used for hundreds of years in China to relieve the recurrence of allergic asthma, and it is still practiced today. Thus, we explored the effect on allergic asthma relapse and the underlying immunoregulatory mechanism in this study. Here, we enrolled 50 allergic asthma participants, and 38 of them completed the treatment and follow-up (the allergic asthma group). In addition, 13 healthy participants (the control group) were enrolled. The recurrence number of allergic asthma participants and asthma control test (ACT) were used to evaluate the effect of treatment on relieving allergic asthma recurrence. Flow cytometry was performed to analyze the levels of Th1 and Th2 cells in the peripheral blood. The serum levels of IgE, IFN-γ, and IL-4 were detected by ELISA. (1) In the allergic asthma group, compared to before the first treatment, the recurrence number of allergic asthma participants decreased and the ACT score increased at end of the last treatment, 18 and 30 weeks of the trial (P < 0.05). At 18 and 30 weeks of the trial, the recurrence number of allergic asthma participants was less and the ACT score was higher than the ones from the same period last year in the allergic asthma group (P < 0.05). Compared to before the first treatment, the percentage of Th1 cell did not change significantly, the percentage of Th2 cell decreased, and the Th1/Th2 cell ratio increased in the allergic asthma group by the end of the last treatment (P < 0.05). Meanwhile, the release of IgE and IL-4 reduced (P < 0.05), and the release of IFN-γ did not significantly change in the allergic asthma group. (2) Compared with the control group, the serum levels of IgE and IL-4 and the percentage of Th2 cell were higher, and the Th1/Th2 cell ratio was lower in the allergic asthma group (P < 0.05). There was no significant difference between Th1 cell and IFN-γ before the first treatment. (3) Compared with the control group, the IgE levels and the percentage of Th2 cell were higher in the allergic asthma group (P < 0.01). Simultaneously, there was no significant difference between Th1 cell, the Th1/Th2 cell ratio, and the serum levels of IFN-γ and IL-4 by the end of the last treatment. The data suggested that RHAS reduced the amount of Th2 cell and elevated the Th1/Th2 cell ratio, thereby alleviating the inflammatory responses in the allergic asthma participants.

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.

Highly Electrically Conductive Three-Dimensional Ti3C2T x MXene/Reduced Graphene Oxide Hybrid Aerogels with Excellent Electromagnetic Interference Shielding Performances.

Two-dimensional transition-metal carbides/carbonitrides (MXenes) with both superb electrical conductivity and hydrophilicity are promising for fabricating multifunctional nanomaterials and nanocomposites. However, the construction of three-dimensional (3D) and lightweight MXene macroscopic assemblies with excellent electrical conductivity and mechanical performances has not been realized due to the weak gelation capability of MXene sheets. Herein, we demonstrate an efficient approach for constructing highly conductive 3D Ti3C2T x porous architectures by graphene oxide assisted hydrothermal assembly followed by directional freezing and freeze-drying. The resultant hybrid aerogels exhibit aligned cellular microstructure, in which the graphene sheets serve as the inner skeleton, while the compactly attached Ti3C2T x sheets present as shells of the cell walls. The porous and highly conductive architecture (up to 1085 S m-1) is highly efficient in endowing epoxy nanocomposite with a high electrical conductivity of 695.9 S m-1 and an outstanding electromagnetic interference (EMI)-shielding effectiveness of more than 50 dB in the X-band at a low Ti3C2T x content of 0.74 vol %, which are the best results for polymer nanocomposites with similar loadings of MXene so far. The successful assembly methodology of 3D and porous architectures of Ti3C2T x would greatly widen the practical applications of MXenes in the fields of EMI shielding, supercapacitors, and sensors.