Relationship between sex differences in drinking, smoking, and exercising and the incidence of malignancies and medical procedures: a cross-sectional study of 21,916 participants in China.

Objectives: The unresolved issue of the relationship between sex differences in tea, coffee, and beverage consumption and malignancy risk prompted our study in 2022. Methods: Logistic proportional hazards models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in our investigation of the associations between cancer risk and tea, coffee, and beverage consumption. Results: Our findings revealed that frequent consumption of white tea significantly reduced the occurrence of malignant tumours, but this effect was detected only in the fully adjusted model for males (OR: 0.736, 95% CI: 0.095-5.704). The amount of sugar added to coffee was associated with an increased risk of malignancy in a dose-dependent manner (P for trend = 0.001), with significance observed for both men (P for trend = 0.049) and women (P for trend = 0.005) in the final model. Notably, individuals who consumed more than 2100 ml of sugary beverages daily had a statistically significant reduction in malignancy risk (OR: 0.219, 95% CI: 0.052-0.917). Interestingly, the intake of sugary beverages had a protective effect on cancer incidence, with a significant effect on males (P for trend = 0.031) but not females (P for trend = 0.096) in the final model. Conclusions: Our study highlights the substantial impact of regular white tea consumption on reducing the risk of malignant tumours in males. This study first reported that the potential protective effect of consuming sugary beverages is predominantly observed in males, and a correlation between the amount of sugar added to coffee and a heightened risk of malignancy.

Electrical switching of Ising-superconducting nonreciprocity for quantum neuronal transistor.

Nonreciprocal quantum transport effect is mainly governed by the symmetry breaking of the material systems and is gaining extensive attention in condensed matter physics. Realizing electrical switching of the polarity of the nonreciprocal transport without external magnetic field is essential to the development of nonreciprocal quantum devices. However, electrical switching of superconducting nonreciprocity remains yet to be achieved. Here, we report the observation of field-free electrical switching of nonreciprocal Ising superconductivity in Fe3GeTe2/NbSe2 van der Waals (vdW) heterostructure. By taking advantage of this electrically switchable superconducting nonreciprocity, we demonstrate a proof-of-concept nonreciprocal quantum neuronal transistor, which allows for implementing the XOR logic gate and faithfully emulating biological functionality of a cortical neuron in the brain. Our work provides a promising pathway to realize field-free and electrically switchable nonreciprocity of quantum transport and demonstrate its potential in exploring neuromorphic quantum devices with both functionality and performance beyond the traditional devices.

On-device phase engineering.

In situ tailoring of two-dimensional materials' phases under external stimulus facilitates the manipulation of their properties for electronic, quantum and energy applications. However, current methods are mainly limited to the transitions among phases with unchanged chemical stoichiometry. Here we propose on-device phase engineering that allows us to realize various lattice phases with distinct chemical stoichiometries. Using palladium and selenide as a model system, we show that a PdSe2 channel with prepatterned Pd electrodes can be transformed into Pd17Se15 and Pd4Se by thermally tailoring the chemical composition ratio of the channel. Different phase configurations can be obtained by precisely controlling the thickness and spacing of the electrodes. The device can be thus engineered to implement versatile functions in situ, such as exhibiting superconducting behaviour and achieving ultralow-contact resistance, as well as customizing the synthesis of electrocatalysts. The proposed on-device phase engineering approach exhibits a universal mechanism and can be expanded to 29 element combinations between a metal and chalcogen. Our work highlights on-device phase engineering as a promising research approach through which to exploit fundamental properties as well as their applications.

Poly(butylene oxalate-co-terephthalate): A PBAT-like but rapid hydrolytic degradation plastic.

Concerns over worldwide plastic pollution have led to the development of biodegradable polyester materials with excellent physical and chemical properties through the copolymerization of poly(butylene oxalate) (PBOx). As a result, poly(butylene oxalate-co-terephthalate)s (PBOTs) with varying compositions, were prepared by incorporating aromatic units. Studies have indicated that PBOT-47 (with a 47% molar terephthalate), exhibits exceptional mechanical properties. With an elongation at break of 1160% and a tensile strength that remains above 30 MPa, similar to or even better than those of the commercial biodegradable plastic poly(butylene adipate-co-terephthalate) PBAT-47 (47% molar terephthalate). Moreover, the permeability coefficients of PBAT-47 for H2O, CO2 and O2 were 5.8, 50.6 and 5.6 times higher than that of PBOT-47, revealing the superior barrier properties of PBOT. Through experimental research and theoretical simulation, the mechanism of the copolymer hydrolysis was elucidated. The readily hydrolytic nature of the oxalate unit endows it with the capacity for rapid degradation, possessing the potential to be a short-term degradable material with physical properties similar to PBAT.

Interfacial magnetic spin Hall effect in van der Waals Fe3GeTe2/MoTe2 heterostructure.

The spin Hall effect (SHE) allows efficient generation of spin polarization or spin current through charge current and plays a crucial role in the development of spintronics. While SHE typically occurs in non-magnetic materials and is time-reversal even, exploring time-reversal-odd (T-odd) SHE, which couples SHE to magnetization in ferromagnetic materials, offers a new charge-spin conversion mechanism with new functionalities. Here, we report the observation of giant T-odd SHE in Fe3GeTe2/MoTe2 van der Waals heterostructure, representing a previously unidentified interfacial magnetic spin Hall effect (interfacial-MSHE). Through rigorous symmetry analysis and theoretical calculations, we attribute the interfacial-MSHE to a symmetry-breaking induced spin current dipole at the vdW interface. Furthermore, we show that this linear effect can be used for implementing multiply-accumulate operations and binary convolutional neural networks with cascaded multi-terminal devices. Our findings uncover an interfacial T-odd charge-spin conversion mechanism with promising potential for energy-efficient in-memory computing.

Metformin improved a heterologous prime-boost of dual-targeting cancer vaccines to inhibit tumor growth in a melanoma mouse model.

Therapeutic cancer vaccines, which induce anti-tumor immunity by targeting specific antigens, constitute a promising approach to cancer therapy. Our previous work proposed an optimized heterologous immunization strategy using cancer gene vaccines co-targeting MUC1 and survivin. Administration of a DNA vaccine three times within a week followed by a single recombinant MVA (rMVA) boost was able to efficiently induce anti-tumor immunity and inhibit tumor growth in tumor-bearing mouse models However, the complex immunosuppressive tumor microenvironment always limits infiltration by vaccine-induced T cells. Modifying the immunosuppressive microenvironment of tumors would be a breakthrough in enhancing the therapeutic effects of a cancer vaccine. Recent studies have reported that metformin, a type 2 diabetes drug, may ameliorate the tumor microenvironment, thereby enhancing anti-tumor immunity. Here, we tested whether the combinational therapeutic strategy of cancer vaccines administered with a heterologous prime-boost strategy with metformin enhanced anti-tumor effects in a melanoma mouse model. The results showed that metformin promoted the transition of M2-tumor-associated macrophages (M2-TAM) to M1-TAM, induced more tumor-infiltrating proliferative CD4 and CD8 T cells, and decreased exhausted T cells. This combinational treatment induced anti-tumor immunity from cancer vaccines, ameliorating the tumor microenvironment, showing improved tumor inhibition, and prolonging survival in tumor-bearing mice compared with either a cancer vaccine or metformin alone.

Cell Membrane-Coated Oncolytic Adenovirus for Targeted Treatment of Glioblastoma.

An oncolytic virus is a promising strategy for glioblastoma (GBM) therapy. However, there are still some challenges such as the blood-brain barrier (BBB) and preexisting immunity for targeted treatment of GBM with an oncolytic virus. In this study, two kinds of cell membrane-coated oncolytic adenoviruses (NCM-Ad and GCM-Ad) were prepared using neural stem cells (NSCs) and GBM cells as sources of membranes, respectively, and were shown to improve the targeted infectivity on GBM cells and avoid the immune clearance of preexisting neutralizing antibodies in vitro and in vivo. Specifically, NCM-Ad showed a strong ability to cross the BBB and target tumor cells in vivo. To improve the cytotoxicity to GBM, a capsid dual-modified oncolytic adenovirus (A4/k37) was also encapsulated, and NCM-A4/k37 showed outstanding tumor targeting and inhibition capacity in an orthotopic xenograft tumor model of GBM upon intravenous administration. This study provides a promising oncolytic virus-based targeted therapeutic strategy for glioma.

Surface-enhanced Raman scattering of a gold core-silver shell-sponge substrate for detection of thiram and diquat.

Aiming at the difficulty of traditional pesticide sampling, a low-cost and convenient flexible surface enhanced Raman scattering (SERS) gold core-silver shell-sponge (Au-Ag-sponge) substrate was synthesized by chemical reduction. The SERS substrate consisted of Au-AgNPs and a melamine sponge. The sponge had a rich open pore structure, which could well "capture" Au-AgNPs, generating a large number of "hot spots". The SERS enhancement activity of the flexible substrate was characterized with rhodamine 6G (R6G) Raman probe molecules. The substrate showed good activity to 10-12 M rhodamine 6G with an enhancement factor (EF) of 7.72 × 106. Applying this substrate to the qualitative and quantitative detection of pesticide residues, the results showed that the Raman intensity was well related to the concentration of pesticide solution with the range of 0.1-10 mg L-1 of thiram and 1-10 mg L-1 of diquat. Furthermore, the substrate was analyzed by finite difference time domain (FDTD) simulation and the results were in good agreement with the experimental results. The reason for the difference in Raman signals of pesticide molecules on the same substrate was the different binding modes of Au-AgNPs on the sponge. Finally, we pointed out the advantages of flexible substrates in the field of pesticide residues, as well as future opportunities and challenges.

Research on a three-dimensional SERS substrate based on a CNTs/Ag@Au/SiO2 composite for detection of fipronil and imidacloprid pesticides.

Surface-enhanced Raman scattering (SERS) has a unique fingerprint spectrum, which allows for rapid, highly sensitive, and non-destructive detection without the need for sample pretreatment. However, SERS substrates have disadvantages such as short storage time and poor reproducibility. In this study, carbon nanotubes, gold, and silver were combined to take advantage of their inherent structural and characteristic properties that enhance the Raman effect. A new type of SERS composite substrate, CNTs/Ag@Au/SiO2, was prepared using a hydrothermal method and seed growth method. The substrate was characterized using transmission electron microscopy (TEM), and the average distance between the core-shell nanoparticles was found to be 3.1 nm, which is more suitable than other gold-silver combined core-shell structures and significantly improves the SERS enhancement factor. The substrate demonstrated high sensitivity even at low concentrations of probe molecules and good uniformity at five randomly selected locations. After storage for 45 days, the substrate still exhibited good stability. In most gold-silver combined core-shell structures, the detection limit for Rhodamine 6G (R6G) is 10-9 mol L-1, while in this substrate, the detection limit for R6G is 10-11 mol L-1. Furthermore, the contribution of the substrate's enhancement was deeply investigated using finite-difference time-domain (FDTD), which revealed that the substrate's hotspots were present in two forms: the "hotspots generated between Ag@Au nanoparticles" and the "hotspots generated between Ag@Au nanoparticles and carbon nanotubes". These two forms of hotspots also demonstrated that the performance brought about by the preparation of the substrate structure was reliable. The simulation results were compared with the experimental results, and the analysis showed that the real environment would have an impact on the substrate's structure during the actual substrate preparation process. Finally, the substrate was used for detecting the pesticide fipronil, and the results showed clear peaks even at a concentration of 0.1 mg L-1. The results indicated that the Raman intensity was linearly exponential with the fipronil solution concentration, with a determination coefficient of R2 = 0.991. This study provides a new SERS substrate for pesticide residue detection and further explores the improvement of pesticide detection limits.

Dose-related immunomodulatory effects of recombinant TRAIL in the tumor immune microenvironment.

BACKGROUND: In addition to specifically inducing tumor cell apoptosis, recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has also been reported to influence the cancer immune microenvironment; however, its underlying effects and mechanisms remain unclear. Investigating the immunomodulatory effects and mechanisms of recombinant TRAIL in the tumor microenvironment (TME) may provide an important perspective and facilitate the exploration of novel TRAIL strategies for tumor therapy. METHODS: Immunocompetent mice with different tumors were treated with three doses of recombinant TRAIL, and then the tumors were collected for immunological detection and mechanistic investigation. Methodological approaches include flow cytometry analysis and single-cell sequencing. RESULTS: In an immunocompetent mouse model, recombinant soluble mouse TRAIL (smTRAIL) had dose-related immunomodulatory effects. The optimal dose of smTRAIL (2 mg/kg) activated innate immune cells and CD8+ T cells, whereas higher doses of smTRAIL (8 mg/kg) promoted the formation of a tumor-promoting immune microenvironment to counteract the apoptotic effects on tumor cells. The higher doses of smTRAIL treatment promoted M2-like macrophage recruitment and polarization and increased the production of protumor inflammatory cytokines, such as IL-10, which deepened the suppression of natural killer (NK) cells and CD8+ T cells in the tumor microenvironment. By constructing an HU-HSC-NPG.GM3 humanized immune system mouse model, we further verified the immunomodulatory effects induced by recombinant soluble human TRAIL (shTRAIL) and found that combinational administration of shTRAIL and trabectedin, a macrophage-targeting drug, could remodel the tumor immune microenvironment, further enhance antitumor immunity, and strikingly improve antitumor effects. CONCLUSION: Our results highlight the immunomodulatory role of recombinant TRAIL and suggest promising therapeutic strategies for clinical application.

How does mandatory energy conversion affect sustainable development: Perspectives of regional heterogeneity and efficiency decomposition.

Clean energy conversion is a core approach and development trend to tackle climate change, while the severe drawbacks such as supply deficiency and cost increase restrict regional sustainable development. This paper employs a natural experiment of coal-to-gas conversion of the Chinese government to study the effect of such policy on regional sustainable development, as well as the underlying mechanism. Based on a city-level dataset from 2006 to 2019, this paper measure green total factor productivity (GTFP) using data envelopment analysis (DEA) combined with the Malmquist‒Luenberger productivity index. Then, this paper evaluates the impact of the CTG policy in pilot cities using the Difference-in-Difference (DID) with Propensity Score Matching (PSM) approach. This paper finds that the CTG policy increased the GTFP of the pilot cities by 2.25% (0.0229/1.02). A series of robustness tests confirmed the findings. Subsequent mechanism analysis shows that the CTG policy increases the GTFP of pilot cities mainly by increasing technical efficiency. In addition, the mechanism of the CTG policy's impact differs between central and noncentral cities. In particular, the CTG policy increases the technological innovation indicator (TC) of provincial capital cities by 2.35% while it increases the technical efficiency indicator (EC) of other cities by 1.89%, which proves the Porter effect in provincial capital cities. Finally, several implications are provided for policymakers to promote other types of renewable energy.

Cascadable in-memory computing based on symmetric writing and readout.

The building block of in-memory computing with spintronic devices is mainly based on the magnetic tunnel junction with perpendicular interfacial anisotropy (p-MTJ). The resulting asymmetric write and readout operations impose challenges in downscaling and direct cascadability of p-MTJ devices. Here, we propose that a previously unimplemented symmetric write and readout mechanism can be realized in perpendicular-anisotropy spin-orbit (PASO) quantum materials based on Fe3GeTe2 and WTe2. We demonstrate that field-free and deterministic reversal of the perpendicular magnetization can be achieved using unconventional charge-to-z-spin conversion. The resulting magnetic state can be readily probed with its intrinsic inverse process, i.e., z-spin-to-charge conversion. Using the PASO quantum material as a fundamental building block, we implement the functionally complete set of logic-in-memory operations and a more complex nonvolatile half-adder logic function. Our work highlights the potential of PASO quantum materials for the development of scalable energy-efficient and ultrafast spintronic computing.

Shifted LT Code Security Scheme for Partial Information Encryption.

The existing physical layer security technology based on fountain codes needs to ensure that the legal channel is superior to the eavesdropping channel; when the quality of the legal channel and the eavesdropping channel are close, the information security cannot be guaranteed. Aiming at this problem, this paper proposes a shifted Luby transform (SLT) code security scheme for partial information encryption, which is mainly divided into two stages, partial information encryption transfer and degree distribution adjustment. The main idea is that the source randomly extracts part of the information symbols, and performs XOR encryption with the random sequence containing the main channel noise sent by the legitimate receiver. Afterward, the degree distribution is adjusted using the number of transfer information symbols received by the legitimate receiver to improve the average degree of the encoded codewords. Since the eavesdropper can only obtain fewer information symbols in the initial stage, it is difficult to decode the generated coded symbols after the degree distribution adjustment, thereby ensuring the safe transmission of information. The experimental results show that, compared with other LT anti-eavesdropping schemes, even if the legitimate channel is not dominant, the proposed scheme still has better security performance and less decoding overhead.

Production of Soluble Murine TRAILs in Escherichia coli with Zn2+ Supplementation.

BACKGROUND: Accumulating evidence has demonstrated the immunomodulatory effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis and the tumor microenvironment, besides its known capacity of specifically inducing the apoptosis of cancer cells. Mice are common available animal models for studying the roles of TRAIL. However, mice express only a single TRAIL receptor (mTRAILR) with an intracellular death domain, in contrast to the two TRAIL receptors (TRAILR1 and TRAILR2) in humans. Moreover, human TRAIL binds weakly to mTRAILR, whereas mouse TRAIL has a high affinity for human TRAIL-Rs. Therefore, we considered that murine TRAIL would be more suitable than human TRAIL for exploring the immunoregulatory effect of TRAIL in immunocompetent mice or when using mouse cells as the target. To our knowledge, the detailed method for the production of recombinant murine TRAIL has not been reported. OBJECTIVE: In this study, we aimed to design and express two soluble forms of murine TRAIL and verify the properties of the protein. METHODS: Recombinant murine TRAILs were expressed in Escherichia coli BL21 (DE3, and Nichelating affinity chromatography was used for protein purification. SDS-PAGE, GDS-PAGE and HPLC were applied to analyze the protein structure. The cytotoxicity of our purified murine TRAILs was evaluated in the TRAIL-sensitive human breast cancer ZR-75-30 cells and murine breast cancer 4T1 cells. Finally, validation of the tumor-killing ability of the murine protein in vivo. RESULTS: Two soluble forms of murine TRAILs (mT_N99 and mT_N188) were purified and demonstrated with high purity and trimeric structure. In addition, Zn2+ supplement was essential to produce soluble murine TRAILs in E.coli BL21 (DE3). The two purified soluble mTRAILs showed similar cytotoxicity to cancer cells, moreover, mT_N99 also showed a good anti-tumor effect in vivo and is more suitable for the treatment of murine tumor models. CONCLUSION: A production approach for recombinant murine TRAIL was determined, which covered the design of shortened forms, expression, purification and characterization.

Clinical features, treatment, and prognosis of 16 breast cancer patients with ocular metastases.

The incidence of ocular metastases in patients with disseminated breast cancer is increasing. This study aimed to investigate the clinical features, treatment, and prognosis of breast cancer patients with ocular metastases. For this purpose, a total of 16 patients were diagnosed with ocular metastases. Demographic, treatment, and other clinical data were obtained from patients' charts. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) statuses of the patients were obtained from the histopathologic reports. Demographic features were analyzed through descriptive statistics, and the Kaplan-Meier method was used for survival analysis. The results showed that among the 16 patients (median age: 41 years), 10 had ER-positive, 8 had PR-positive, and 3 had HER2-positive disease. The choroid was the most commonly involved structure (n = 8). Nine (56%) patients had blurred vision. Treatments for these patients included systemic therapy (six patients), radiotherapy (three patients), and combined therapy (seven patients). The median time from the diagnosis of breast cancer to the diagnosis of ocular metastasis was 52.9 months, and the median time from the diagnosis of metastatic breast cancer at any other site to the diagnosis of ocular metastasis was 21.3 months. The median overall survival (OS) was 136.5 months (95% confidence interval, 40.6-232.4 months), and the median survival duration after ocular metastasis was 32.4 months (95% confidence interval, 20.1-44.7 months). The OS of patients with unilateral eye involvement and bilateral eye involvement did not differ significantly (P = 0.573), nor did the OS of those diagnosed before 2000 and in 2000 or later (P = 0.409). In general, a breast cancer patient with ocular metastasis can have a good prognosis after therapy. However, large-scale clinical studies are needed to confirm our findings.

Lipid Profiles of the Heads of Four Shrimp Species by UPLC-Q-Exactive Orbitrap/MS and Their Cardiovascular Activities.

Lipids are key factors in nutrition, structural function, metabolic features, and other biological functions. In this study, the lipids from the heads of four species of shrimp (Fenneropenaeus chinensis (FC), Penaeus japonicus (PJ), Penaeus vannamei (PV), and Procambarus clarkia (PCC)) were compared and characterized based on UPLC-Q-Exactive Orbitrap/MS. We compared the differences in lipid composition of four kinds of shrimp head using multivariate analysis. In addition, a zebrafish model was used to evaluate pro-angiogenic, anti-inflammatory, anti-thrombotic, and cardioprotective activities of the shrimp head lipids. The lipids from the four kinds of shrimp head had different degrees of pro-angiogenic activities, and the activities of PCC and PJ shrimp lipids were more significant than those of the other two species. Four lipid groups displayed strong anti-inflammatory activities. For antithrombotic activity, only PCC (25 µg/mL) and PV (100 µg/mL) groups showed obvious activity. In terms of cardioprotective activity, the four kinds of lipid groups significantly increased the zebrafish heart rhythms. The heart distances were shortened, except for those of the FC (100 µg/mL) and PJ (25 µg/mL) groups. Our comprehensive lipidomics analysis and bioactivity study of lipids from different sources could provide a basis for the better utilization of shrimp.

Heterologous prime-boost immunization co-targeting dual antigens inhibit tumor growth and relapse.

Therapeutic cancer vaccines aim to induce an effective immune response against cancer, and the effectiveness of these vaccines is influenced by the choice of immunogen, vaccine type, and immunization strategy. Although treatment with cancer vaccines can improve tumor burden and survival, in most animal studies, it is challenging to achieve a complete response against tumor growth and recurrence, without the use of other therapies in combination. Here, we present a novel approach where dual antigens (survivin and MUC1) are co-targeted using three DNA vaccines, followed by a single booster of a recombinant modified vaccinia Ankara (MVA) vaccine. This heterologous vaccination strategy induced higher levels of interferon (IFN)-γ-secretion and stronger antigen-specific T-cell responses than those induced individually by the DNA vaccines and the MVA vaccine in mice. This strategy also increased the number of active tumor-infiltrating T cells that efficiently inhibit tumor growth in tumor-bearing mice. Heterologous DNA prime-MVA boost immunization was capable of inducing a robust antigen-specific immune-memory, as seen from the resistance to subsequent survivin- and MUC1-expressing tumors. Moreover, the therapeutic effects of DNA prime-MVA boost and DNA prime-adenovirus boost strategies were compared. DNA prime-MVA boost immunization performed better, as indicated by the T effector ratio and the induction of Th1 immunity. This study provides the basis for the use of heterologous DNA prime-MVA boost vaccination regime targeting two antigens simultaneously as a promising immunotherapeutic strategy against cancer.

A tropism-transformed Oncolytic Adenovirus with Dual Capsid Modifications for enhanced Glioblastoma Therapy.

Glioblastoma, the most common human brain tumor, is highly invasive and difficult to cure using conventional cancer therapies. As an alternative, adenovirus-mediated virotherapies represent a popular and maturing technology. However, the cell surface coxsackievirus and adenovirus receptor (CAR)-dependent infection mechanism limits the infectivity and oncolytic effects of Adenovirus type 5. To address this limitation, in this study we aimed to develop a novel oncolytic adenovirus for enhanced infectivity and therapeutic efficacy toward glioblastoma. We developed a novel genetically modified oncolytic adenovirus vector with dual capsid modifications to facilitate infection and specific cytotoxicity toward glioma cells. Modification of the adenoviral capsid proteins involved the incorporation of a synthetic leucine zipper-like dimerization domain into the capsid protein IX (pIX) of human adenovirus serotype 5 (Ad5) and the exchange of the fiber knob from Ad37. The virus infection mechanism and anti-tumor efficacy of modified vectors were evaluated in both in vitro (cell) and in vivo (mouse) models. Ad37-knob exchange efficiently promoted the virus infection and replication-induced glioma cell lysis by oncolytic Ad5. We also found that gene therapy mediated by the dual-modified oncolytic Ad5 vector coupled with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This genetically modified oncolytic adenovirus provides a promising vector for future use in glioblastoma gene-viral-based therapies.

Strain-Sensitive Magnetization Reversal of a van der Waals Magnet.

By virtue of the layered structure, van der Waals (vdW) magnets are sensitive to the lattice deformation controlled by the external strain, providing an ideal platform to explore the one-step magnetization reversal that is still conceptual in conventional magnets due to the limited strain-tuning range of the coercive field. In this study, a uniaxial tensile strain is applied to thin flakes of the vdW magnet Fe3 GeTe2 (FGT), and a dramatic increase of the coercive field (Hc ) by more than 150% with an applied strain of 0.32% is observed. Moreover, the change of the transition temperatures between the different magnetic phases under strain is investigated, and the phase diagram of FGT in the strain-temperature plane is obtained. Comparing the phase diagram with theoretical results, the strain-tunable magnetism is attributed to the sensitive change of magnetic anisotropy energy. Remarkably, strain allows an ultrasensitive magnetization reversal to be achieved, which may promote the development of novel straintronic device applications.

Enhancing the antitumor activity of an engineered TRAIL-coated oncolytic adenovirus for treating acute myeloid leukemia.

The use of oncolytic viruses has emerged as a promising therapeutic approach due to the features of these viruses, which selectively replicate and destroy tumor cells while sparing normal cells. Although numerous oncolytic viruses have been developed for testing in solid tumors, only a few have been reported to target acute myeloid leukemia (AML) and overall patient survival has remained low. We previously developed the oncolytic adenovirus rAd5pz-zTRAIL-RFP-SΔ24E1a (A4), which carries the viral capsid protein IX linked to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and results in increased infection of cancer cells and improved tumor targeting. To further improve the therapeutic potential of A4 by enhancing the engagement of virus and leukemia cells, we generated a new version of A4, zA4, by coating A4 with additional soluble TRAIL that is fused with a leucine zipper-like dimerization domain (zipper). ZA4 resulted in enhanced infectivity and significant inhibition of the proliferation of AML cells from cell lines and primary patient samples that expressed moderate levels of TRAIL-related receptors. ZA4 also elicited enhanced anti-AML activity in vivo compared with A4 and an unmodified oncolytic adenoviral vector. In addition, we found that the ginsenoside Rh2 upregulated the expression of TRAIL receptors and consequently enhanced the antitumor activity of zA4. Our results indicate that the oncolytic virus zA4 might be a promising new agent for treating hematopoietic malignancies such as AML.