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OBJECTIVE Immune checkpoint-inhibitory therapeutic antibodies have shown striking activity against several types of cancers but are less effective against brain-localized malignancies, in part due to the protective effect of the blood-brain barrier (BBB). The authors hypothesized that intraarterial (IA) delivery of a novel compound, NEO100, has the potential to safely and reversibly open the BBB to enable brain-targeted therapeutic activity of checkpoint-inhibitory antibodies. METHODS Immunocompetent mice with syngeneic glioblastoma or melanoma cells implanted into their brains were subjected to a single IA injection of NEO100 to open their BBB. One dose of murine anti–PD-1/PD-L1 antibody was either coinjected with NEO100 or separately injected intravenously. Brain penetration of these antibodies and levels of CD8+ T cell infiltrate into the tumor microenvironment were quantitated and animal survival was monitored. RESULTS IA NEO100 enabled the increased accumulation of checkpoint-inhibitory antibodies in the brain, along with greater numbers of T cells. In both malignancy models, a single intervention of IA NEO100 combined with antibody resulted in the long-term survival of animals. Antibody treatment in the absence of NEO100 was far less effective. CONCLUSIONS BBB opening by IA NEO100 facilitates brain tumor access by checkpoint-inhibitory antibodies and enables their therapeutic activity, along with increased levels of T-cell recruitment.

Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors α-globulin, γ-globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of α-globulin, γ-globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.

BACKGROUND Glioblastoma has a high degree of malignancy and poor prognosis. It is common to have in situ recurrence and intracranial metastasis, while extracranial metastasis is rare, and extracranial multiorgan metastasis is extremely rare. We report a case of glioblastoma with extracranial multiorgan metastasis, which will strengthen clinicians’ attention to the extracranial metastasis of glioblastoma and its treatment. CASE SUMMARY A male patient visited our hospital for treatment of dizziness and headache. Magnetic resonance imaging of the brain revealed a space-occupying lesion in the right temporoparietal occipital region. Chest computed tomography and abdominal ultrasound were normal, and no space-occupying lesions were observed in other organs of the body. The patient underwent surgery and diagnosed with glioblastoma. Postoperative concurrent radiotherapy and chemotherapy were completed. During the follow-up, the tumor was found to have metastasized to the scalp and neck, and a second tumor resection was performed. Postoperative follow-up revealed extracranial metastases to multiple extracranial organs including skull, scalp, ribs, spine, liver and lung. His family members refused further treatment, and requested only symptomatic treatment such as pain relief, and the patient died of systemic multiple organ failure. Survival time from diagnosis to death was 13 mo and from extracranial metastasis to death was 6 mo. CONCLUSION Glioblastoma extracranial metastasis is extremely rare, clinicians should always pay attention to its existence. The mechanism of glioblastoma extracranial metastasis is still unclear, and genetic and molecular studies are required.

van der Waals heterostructures combining perovskites of strong light absorption with atomically thin two-dimensional (2D) transition-metal dichalcogenides (TMDs) hold great potential for light-harvesting and optoelectronic applications. However, current research studies integrating TMDs with low-dimensional perovskite nanomaterials generally suffer from poor carrier/energy transport and harnessing, stemming from poor interfacial interaction due to the nanostructured nature and ligands on surface/interface. To overcome the limitations, here, we report prototypical three-dimensional (3D)/2D perovskite/TMD heterostructures by combing highly smooth and ligand-free CsPbBr3 film with a WSe2 monolayer. We show that the energy transfer at interface occurs through asymmetric two-step charge-transfer process, with ultrafast hole transfer in ∼200 fs and subsequent electron transfer in ∼10 ps, driven by the asymmetric type I band alignment. The energy migration and transfer from CsPbBr3 film to WSe2 can be well described by a one-dimensional diffusion model with a carrier diffusion length of ∼500 nm in CsPbBr3 film. Thanks to the long-range carrier migration and ultrafast interfacial transfer, highly efficient (>90%) energy transfer to WSe2 can be achieved with CsPbBr3 film as thick as ∼180 nm, which can capture most of the light above its band gap. The efficient light and energy harvesting in perovskite/TMD 3D/2D heterostructures suggest great promise in optoelectronic and photonic devices.

Glioma is a primary brain tumor with limited treatment approaches and glioblastoma stem cells (GSCs) are manifested with the self-renewal capability and high tumorigenic capacity. This study was performed to investigate the regulatory effect of the SUMO-specific protease 1 (SENP1)/methyltransferase-like 3 (METTL3)/MYC axis on the self-renewal of GSCs mediated by transcription factor Yin Yang 1 (YY1). Following bioinformatics analysis and clinical and cellular experiments, we found that YY1 was highly expressed in GBM tissues and cells, while silencing its expression reduced the self-renewal ability of GSCs. Functionally, YY1 promoted the transcriptional expression of SENP1 by binding to the promoter region of SENP1, while the deSUMOase SENP1 facilitated the methylase activity of m6A through deSUMOylation of the methylase METTL3, thereby promoting the m6A modification of MYC mRNA via METL3 and promoting the expression of MYC. A nude mouse xenograft model of GBM was also constructed to examine the tumorigenicity of GSCs. The obtained findings demonstrated that YY1 promoted tumorigenicity of GSCs by promoting the expression of MYC in vivo. Conclusively, YY1 can transcriptionally upregulate the SUMOylase SENP1 and enhance the methylase activity of METTL3, resulting in the increased m6A modification level of MYC mRNA, thereby promoting the self-renewal of GSCs.

Background: Due to the high nursing pressure of patients with Cerebral hemorrhage and the general shortage of clinical nurses, nursing support workers often participate in clinical nursing work, but the influence of nursing support workers' participation on the negative emotion, quality of life and life satisfaction of patients with intracerebral hemorrhage is unknown. Methods: A total of 107 ICH patients admitted to our hospital from January 2022 to March 2022 were enrolled, including 60 patients receiving conventional care (CG control group) and 47 patients receiving nursing support worker participation (RG research group). All patients were recorded with self-perceived Burden Scale (SPBS), Hamilton Depression Scale (HAMD), Quality of Life Scale (SF-36), Somatic Self rating Scale (SSS), Patient self-care ability assessment scale（Barthel）and Satisfaction with life scale (SWLS) scores. Results: Patients with high negative emotion were more willing to participate in clinical nursing work (P). Nursing support workers involved in cerebral hemorrhage patients can alleviate negative emotions, improve life quality, improve nursing satisfaction (P). Conclusion: The participation of nursing support workers can alleviate the negative emotions of ICH patients, enhance their self-management ability, and improve their life quality.

Background: The level of thyroid hormones (TH) influences the prognosis of a wide range of diseases. Despite this, to date, there have been few studies that have evaluated the effect of TH levels on the prognosis of patients with multiple myeloma (MM). As a result, we investigated the effect of TH levels on survival in patients with MM.Methods: TH levels and common adverse prognostic markers were compared in 124 newly diagnosed MM patients. To evaluate differences between categorical and continuous variables, Chi-Square test and Fisher's Exact test as well as Mann-Whitney U test were used. Kaplan-Meier test was used for survival analysis, and Cox proportional risk regression was used for univariate and multivariate analysis of overall survival (OS).Results: A significant decrease in total thyroxine (TT4) and total triiodothyronine (TT3) was observed in patients with multiple myeloma (P Conclusions: Thyroid hormone levels, particularly TT4, may be an important predictor of poor prognosis in patients with MM.

Light-emitting silicon nanomaterials are actively pursued to exploit their photonic applications. However, the preparation of efficient blue emissive silicon nanomaterials has remained a challenge because of the difficulties in controlling the ultrasmall diameter and passivating the large-area surface of the nanomaterials. Here, we report highly stable deep-blue emissive silicene-like quantum dots (silicene-like QDs) with a photoluminescence quantum yield of above 70%, representing the most efficient blue emissive silicon nanomaterial. The new structure of the silicene-like QDs that possesses a two-dimensional silicon backbone with a reduced lateral size provides a feasible way to enhance the quantum confinement effect. A method of hydrofluoric acid etching enables the preparation of this new structure, which simultaneously reduces defect density of the silicene-like QDs and thus enhances radiative recombination of electron–hole pairs. Furthermore, we demonstrate a deep-blue emissive LED based on the silicene-like QDs, showing a maximum luminance of larger than 2000 cd m−2. Our results open the door towards the silicene-like QDs as outstanding optical and optoelectronic materials.

ZnO/ZnMgO MQWs was employed as an active layer to fabricate p-GaN/MQWs/n-ZnO diode by molecular beam epitaxy. It showed sharp and efficient UV emission around 370 nm due to constraint of carriers in high-quality MQWs well layer.

Tumor immunotherapy has the advantages of high specificity, minimal damage to the patient's body, and a long-lasting anti-tumor effect. However, due to the existence of immune escape phenomenon, the effect of anti-tumor immunotherapy is still poor. Therefore, a cancer vaccine that reverses tumor-associated immunosuppression is a very promising approach for research and treatment.Vaccines were prepared using autologous and allogeneic tumor cells and their lysates to syngeneic tumor cell lysates as immunogens. The glioma cell proliferation, apoptosis and the secretion level of MCP-2, IFN-γ were detected to evaluate the efficacy of this treatment against glioma in vitro. In addition, a rat glioma model was established to investigate the anti-tumor effect in vivo, and evaluated its efficacy by observing the changes of CD4 + T cells, CD8 + T cells, NK cells, and the level of IL-2 and IL-10 in peripheral blood before and after treatment.The C6 + 9L glioma cell lysate vaccine (C6 + 9L-CL) not only inhibited the proliferation of glioma cells and promoted their apoptosis in vitro, but also significantly inhibited the tumor growth in vivo and improved the survival time of rats. In addition, the C6 + 9L-CL vaccine enhanced the anti-tumor immune response by promoting the secretion of T cell chemokines MCP-2, IFN-γ and IL-2, and by stimulating the proliferation of T cells and NK cells in peripheral blood and glioma tissues.Our findings demonstrate the inhibitory effect of molecular mimic vaccines on glioma and provided a theoretical basis for molecular mimic hybrid vaccines as a potential therapeutic approach.

Background Intracarotid injection of mannitol has been applied for decades to support brain entry of therapeutics that otherwise do not effectively cross the blood–brain barrier (BBB). However, the elaborate and high-risk nature of this procedure has kept its use restricted to well-equipped medical centers. We are developing a more straightforward approach to safely open the BBB, based on the intra-arterial (IA) injection of NEO100, a highly purified version of the natural monoterpene perillyl alcohol. Methods In vitro barrier permeability with NEO100 was evaluated by transepithelial/transendothelial electrical resistance and antibody diffusion assays. Its mechanism of action was studied by western blot, microarray analysis, and electron microscopy. In mouse models, we performed ultrasound-guided intracardiac administration of NEO100, followed by intravenous application of Evan’s blue, methotrexate, checkpoint-inhibitory antibodies, or chimeric antigen receptor (CAR) T cells. Results NEO100 opened the BBB in a reversible and nontoxic fashion in vitro and in vivo. It enabled greatly increased brain entry of all tested therapeutics and was well tolerated by animals. Mechanistic studies revealed effects of NEO100 on different BBB transport pathways, along with translocation of tight junction proteins from the membrane to the cytoplasm in brain endothelial cells. Conclusion We envision that this procedure can be translated to patients in the form of transfemoral arterial catheterization and cannulation to the cerebral arteries, which represents a low-risk procedure commonly used in a variety of clinical settings. Combined with NEO100, it is expected to provide a safe, widely available approach to enhance brain entry of any therapeutic.

Background Conventional immunotherapy for glioma is not only expensive but also demonstrates less-than-desired clinical efficacy. In this study, we evaluated the immunotherapeutic efficacy of a tumor cell lysate-based hybrid glioma vaccine developed using a molecular-based approach. Methods First, the ability of the autologous (9L-cell lysate) and allogeneic (C6-cell lysate) vaccines against glioma, individually and in combination, to activate Fischer344 rat dendritic cells (DCs) was determined. Next, the activated DCs were co-cultured with T lymphocytes and screened for the optimal DC-to-T-cell ratio. The in vitro efficacy of the DC/T-cell vaccine formulations subjected to different immunogen treatments and co-cultured with glioma cells was evaluated based on glioma cell viability and monocyte chemoattractant protein (MCP)-2 and interferon (IFN)-γ secretion. Subsequently, the efficacy of the 9L + C6 hybrid vaccine was evaluated in 32 glioma rat models, randomly allocated to the following five treatment groups: blank control, tumor, vaccine treatment, thymosin treatment, and vaccine + thymosin treatment (combined treatment). Changes in survival duration, intracranial tumor volume, peripheral blood immune-cell (CD4+ T, CD8+ T, and natural killer [NK] cell) count, and serum cytokine (interleukin [IL]-2, IL-10) levels were assessed in these groups. Results The hybrid vaccine demonstrated the highest glioma cell apoptosis and the lowest cell viability and promoted MCP-2 and IFN-γ secretion in vitro. The vaccine treatment and combined treatment groups demonstrated longer survival duration, lower intracranial tumor volume, and higher immune cell glioma tissue infiltration and IL-2 secretion than the untreated tumor group, indicating the vaccine's good in vivo efficacy. Thymosin treatment had minimal effect in enhancing anti-glioma immunity. Conclusion We demonstrated the feasibility of combining autologous and allogeneic tumor cell lysates to stimulate specific host cell immune response against glioma cells. The good clinical efficacy of our developed glioma hybrid vaccine in rat models suggests its potential clinical application.

Over the past decade, increasing researches have demonstrated the implication of microRNAs (miRNAs or miRs) in tumorigenicity of glioma stem cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. Herein, we aim to investigate the role of miR-30a in the proliferation and self-renewal of GSCs and the possible mechanism in relation to ecto-5'-nucleotidase (NT5E)-dependent Akt signaling pathway. RT-qPCR and Western blot analysis were performed to determine the expression of miR-30a and NT5E in glioma tissues and cell lines. GSCs were isolated from glioma cells and identified using flow cytometry. The relationship between miR-30a and NT5E was determined by dual-luciferase reporter gene assay. Gain- and loss-of-function experiments were performed to examine the effects of miR-30a and NT5E on sphere formation, colony formation, and proliferation of GSCs in vitro, as well as orthotopic tumor growth of GSCs in nude mice. Additionally, the Akt signaling pathway was blocked with an Akt inhibitor, LY294002, to investigate its involvement in the regulatory effect of miR30a. miR-30a was poorly expressed in glioma tissues and cell lines as well as GSCs. NT5E, highly expressed in GSCs, was identified as a target of miR-30a. In addition, miR-30a upregulation or NT5E silencing could reduce GSC sphere formation, clone formation, proliferation, and orthotopic tumor growth in nude mice. Moreover, miR-30a inhibited the activation of the Akt signaling pathway by targeting NT5E, and ultimately suppressing the self-renewal and orthotopic tumor growth of GSCs. Our results demonstrate that miR-30a targets NT5E to inhibit the Akt signaling pathway, by which could suppress the self-renewal and orthotopic tumor growth of GSCs. Those findings may provide theoretical basis of miR-30a as a therapeutic target to suppress the glioma progression.

Lead halide perovskites are promising semiconductors for various optoelectronic devices working in a wide photo-excitation density regime. However, photo-induced instability, attributed to illumination-activated mobile ions, has been an obstacle to their application. Herein, we use the time evolution of photoluminescence (PL) to investigate the light illumination effects of CH3NH3PbBr3 perovskite films under relatively high excitation (up to 4.5 W cm−2). We demonstrate that continuous illumination can lead to both PL enhancement and PL quenching simultaneously, with their weight ratios depending on the excitation density. The experimental data can be well described and interpreted by considering the coexistence of and competition between the photo-induced annihilation and the formation of long-living filled trap states. Our study may provide in-depth insight into the photo-induced instability of perovskite films and help to improve the performance of perovskite-based optoelectronic devices.

Two-dimensional silicon-based materials have unique physical and chemical properties due to high surface area and quantum confinement effects. Herein, a topochemical reaction method is used for preparing silicene quantum dots confined in few layer siloxene nanosheets with FeCl3·6H2O as oxidant, which shows a thickness less than 2 nm. The experimentally prepared siloxene nanosheets are dispersible, with silicene quantum dots having an average diameter less than 5 nm. The silicene quantum dots are self-organized through the oxidation of FeCl3, showing unique optical properties of blue emission. The UV–visible absorption and PL emission spectra indicate the quasi-direct band gap transition to the emission. Besides, the few-layer siloxene nanosheets with silicene quantum dots have a radiative lifetime of 1.098 ns at an emission wavelength of 435 nm, which derives from the quasi-direct band transition of silicene quantum dots. Such two-dimensional nanosheets of silicon possess potential applications for the em...

Colloidal all-inorganic perovskite CsPbBr3 nanocrystals present versatile outstanding optoelectronic properties as well as greatly improved stability when compared with their hybrid analogues. Howe...

A simple and efficient method to grow continuous large-area ZnO/MoS2 heterostructures is demonstrated by pulsed laser deposition. The layer number of MoS2 films is controlled by the number of laser pulses. The MoS2 film acts as a closely lattice-matched buffer layer for the subsequent ZnO growth, which improves the structural and optical quality of the ZnO film. ZnO film and multilayer MoS2 forms a type-II heterostructure, and the band offsets between them are quantitatively determined.

An efficient and general method for the synthesis of 3-sulfenylindoles and 3-selenylindoles employing visible-light irradiation with graphene oxide as a promoter at room temperature has been achieved. The reaction features are high yields, simple operation, metal-free and iodine-free conditions, an easy-to-handle oxidant, and gram-scalable synthesis. This simple protocol allows one to access a wide range of 3-arylthioindoles, 3-arylselenylindoles, and even 3-thiocyanatoindoles with good to excellent yields.

Description, Oriented nanoplatelets improve light extraction, enabling perovskite light-emitting diodes with high efficiency., Solution-processed planar perovskite light-emitting diodes (LEDs) promise high-performance and cost-effective electroluminescent devices ideal for large-area display and lighting applications. Exploiting emission layers with high ratios of horizontal transition dipole moments (TDMs) is expected to boost the photon outcoupling of planar LEDs. However, LEDs based on anisotropic perovskite nanoemitters remain to be inefficient (external quantum efficiency, EQE

Microplastics (wasted plastic particles5 mm in diameter) are ubiquitously distributed in the marine environment. Filter-feeding and low trophic level bivalves are vulnerable to microplastics accumulation from the surrounding depositional environment, thereby threatening both ecological health and human food safety. Microplastics had been detected in lots of coastal Bivalvia species. However, the influence of biological morphology on the mechanism of microplastics accumulation is not clear. There is also a knowledge gap of which species are preferred for commercial consumption, which creates loopholes in risk identification for food safety. A survey on a commercial popular eaten but under-researched hard clam (Meretrix meretrix; Linnaeus, 1758) from a famous fishery port city in southern China was carried out to comprehensively analyze shell size influence on microplastics accumulation in bivalves and consequently, human intake risk via bivalve consumption. Detected microplastics count in per individual (MCI) was 24.64 ± 19.11 items · individual

Background: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. Methods: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. Results: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. Conclusion: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.

Solution-processed all-inorganic CsPbX3 perovskites exhibit outstanding optoelectronic properties and are being considered as a promising optical gain medium, with impressive performance in the green and red region. However, the development of CsPbX3 for blue emission is still lagging far behind, owing to difficulties in thin films synthesis and spectral instability subject to light irradiation. Here, a facile vapor anion exchange (VAE) method that enables preparation of blue-emitting perovskite films with both excellent surface morphology and good photo-stability is reported. The mixed-Br/Cl quasi-2D perovskite films show spectrally stable pure blue emission (471 nm) under continuous-wave laser irradiation with power density as high as 81 W cm-2 . Furthermore, optically pumped blue amplified spontaneous emission (ASE) is realized based on the mixed-Br/Cl perovskite films. By changing the duration of VAE treatment, the ASE peak can be tuned from 537 nm down to 475 nm. This work not only presents a facile method to prepare high quality mixed halide Cs-based perovskite films, but also pave the way for further exploration of stable blue perovskite lasing.