Insight into Interfacial Heat Transfer of ß-Ga2O3/Diamond Heterostructures via the Machine Learning Potential.

ß-Ga2O3 is an ultrawide-band gap semiconductor with excellent potential for high-power and ultraviolet optoelectronic device applications. Low thermal conductivity is one of the major obstacles to enable the full performance of ß-Ga2O3-based devices. A promising solution for this problem is to integrate ß-Ga2O3 with a diamond heat sink. However, the thermal properties of the ß-Ga2O3/diamond heterostructures after the interfacial bonding have not been studied extensively, which are influenced by the crystal orientations and interfacial atoms for the ß-Ga2O3 and diamond interfaces. In this work, molecular dynamics simulations based on machine learning potential have been adopted to investigate the crystal-orientation-dependent and interfacial-atom-dependent thermal boundary resistance (TBR) of the ß-Ga2O3/diamond heterostructure after interfacial bonding. The differences in TBR at different interfaces are explained in detail through the explorations of thermal conductivity value, thermal conductivity spectra, vibration density of states, and interfacial structures. Based on the above explorations, a further understanding of the influence of different crystal orientations and interfacial atoms on the ß-Ga2O3/diamond heterostructure was achieved. Finally, insightful optimization strategies have been proposed in the study, which could pave the way for better thermal design and management of ß-Ga2O3/diamond heterostructures according to guidance in the selection of the crystal orientations and interfacial atoms of the ß-Ga2O3 and diamond interfaces.

In situ autophagy regulation in synergy with phototherapy for breast cancer treatment.

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the "self-guidance system", Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Interfacial Optimization for AlN/Diamond Heterostructures via Machine Learning Potential Molecular Dynamics Investigation of the Mechanical Properties.

AlN/diamond heterostructures hold tremendous promise for the development of next-generation high-power electronic devices due to their ultrawide band gaps and other exceptional properties. However, the poor adhesion at the AlN/diamond interface is a significant challenge that will lead to film delamination and device performance degradation. In this study, the uniaxial tensile failure of the AlN/diamond heterogeneous interfaces was investigated by molecular dynamics simulations based on a neuroevolutionary machine learning potential (NEP) model. The interatomic interactions can be successfully described by trained NEP, the reliability of which has been demonstrated by the prediction of the cleavage planes of AlN and diamond. It can be revealed that the annealing treatment can reduce the total potential energy by enhancing the binding of the C and N atoms at interfaces. The strain engineering of AlN also has an important impact on the mechanical properties of the interface. Furthermore, the influence of the surface roughness and interfacial nanostructures on the AlN/diamond heterostructures has been considered. It can be indicated that the combination of surface roughness reduction, AlN strain engineering, and annealing treatment can effectively result in superior and more stable interfacial mechanical properties, which can provide a promising solution to the optimization of mechanical properties, of ultrawide band gap semiconductor heterostructures.

A "bulldozer" driven by anoxic bacteria for pancreatic cancer chemo-immunotherapy.

Immune evasion is a major obstacle for pancreatic ductal adenocarcinoma (PDAC) therapy. Inhibition of autophagy can improve antigen presentation and enlarge immunogenic cell death (ICD) effect to generate a strong anti-tumor immune response. However, abundant extracellular matrix dominated by hyaluronic acid (HA) hinders the deep penetration of autophagy inhibitors and ICD inducers. Herein, an intelligent autophagy inhibitor hydroxychloroquine (HCQ) and chemotherapeutic drug doxorubicin (DOX) co-loaded "bulldozer" (HD@HH/EcN) driven by anoxic bacteria was constructed for PDAC chemo-immunotherapy. Results demonstrated that probiotic Escherichia coli 1917 (EcN) could carry hyaluronidases (HAases)-hybrided albumin nanoparticles (HD@HH) to reach PDAC tumor tissue quickly and accurately. Thereafter, HAases can efficiently cleave the tumor matrix barrier and promote HD@HH/EcN to accumulate at tumor hypoxic core significantly. After that, high level of glutathione (GSH) in tumor microenvironment (TME) induces intermolecular disulfide bond in HD@HH nanoparticles breakage, to precisely release HCQ and DOX. DOX can induce ICD effect. Meanwhile, HCQ can amplify DOX induced ICD effect by inhibiting tumor autophagy, which further increase cell surface expression of major histocompatibility complex class I (MHC-I) and augment recruitment of CD8+ T cell to improve immunosuppressive TME. This study provides a new strategy for PDAC chemo-immunotherapy.

A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer.

Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe3+ was reduced to Fe2+by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H2O2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V0 of 2.19 ±â€¯0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.

Association of three micro-RNA gene polymorphisms with the risk of cervical cancer: a meta-analysis and systematic review.

OBJECTIVE: Regulation of single nucleotide polymorphisms (SNP) in micro-RNA (miRNA) on the host cells may be one of the most important factors influencing the occurrence of cervical cancer based on the prevalence of HPV infection and the development of cervical cancer. In order to explore the contribution of miRNA polymorphism to the occurrence and development of cervical cancer, we conducted an analytical study. METHODS: We selected the polymorphisms of three widely studied miRNAs (miRNA-146a rs2910164, miRNA-499 rs3746444, and miRNA-196a2 rs11614913). Then, we conducted a meta-analysis (for the first time) to investigate their susceptibility to cervical cancer. Case control studies on the correlation between these three miRNAs and cervical cancer susceptibility were investigated by searching on from Pubmed, The Cochrane Library, Embase, CBM, CNKI, Wanfang database, and VIP database. Basic characteristics were recorded and meta-analysis of the case studies was performed using the STATA 15.1 software. RESULTS: The miRNA-146a rs2910164 mutation significantly reduced the risk of cervical cancer in both recessive model (OR = 0.804, 95% CI = 0.652-0.992, P = 0.042; CC vs. CG+GG) and allelic model (OR = 0.845, 95% CI = 0.721-0.991, P = 0.038; C vs. G). There was no significant correlation between miRNA-499 rs3746444 and the risk of cervical cancer. The miRNA-196a2 rs11614913 mutation was significantly associated with a reduced risk of cervical cancer in homozygous model (OR = 0.641, 95% CI = 0.447-0.919, P = 0.016; TT vs. CC), dominant model (OR = 0.795, 95% CI = 0.636-0.994, P = 0.045; CT+TT vs. CC), recessive model (OR = 0.698, 95% CI = 0.532-0.917, P = 0.01; TT vs. CC+CT), and allelic models (OR = 0.783, 95% CI = 0.643-0.954, P = 0.015, T vs. C). CONCLUSION: In summary, this meta-analysis shows that the mutant genotypes of miRNA-146a rs2910164 and miRNA-196a2 rs11614913 are associated with a reduced risk of cervical cancer. Therefore, they may be two gene regulatory points for the prevention of cervical cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021270079.