Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Roles of post-translational modifications of UHRF1 in cancer.

UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.

ATM-Mediated translocation of RanBPM regulates DNA damage response by stabilizing p21 in non-small cell lung cancer cells.

PURPOSE: Platinum-based chemotherapy remains a standard-of-care for most patients with advanced non-small cell lung cancer (NSCLC). DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. Previous studies have reported that RanBPM has been involved in various cellular processes such as DDR by interacting with multiple proteins. However, the underlying mechanism remains unclear. METHODS: NSCLC tissue microarrays were used for assessing the expression of RanBPM by immunohistochemical staining. The roles of RanBPM in the DDR of NSCLC progression was examined in in vitro cell lines and in vivo animal models. The regulation of RanBPM on protein stability and ubiquitination levels were investigated by immunoblots and in vivo ubiquitylation assay. RESULTS: The level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation. Mechanistically, RanBPM protein physically interacts with p21, and RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. RanBPM silencing significantly decreased p21 protein level. Conversely, RanBPM overexpression led to the accumulation of endogenous p21 protein regardless of p53 status. Functionally, RanBPM regulates DDR in a p21-dependent manner. Furthermore, DNA damage significantly promoted the nuclear translocation of RanBPM protein through ATM signaling pathways. CONCLUSION: RanBPM is a novel regulator of P21 protein stability, and plays a critical role in the regulation of DDR.

Nonreciprocal dynamics of noninteracting ultracold atoms in a momentum lattice.

Realization of nonreciprocal transport is of great importance in the development of devices and systems that require the directional manipulation of signals or particles in information processing and modern physics. For ultracold atomic systems, the approaches based on synthetic dimensions have led to rapid advances in engineering quantum transport. Here, we use laser-coupled discrete momentum states of noninteracting ultracold atoms to synthesize a momentum lattice, and construct a closed ring with controllable tunneling phase in the momentum lattice. We measure the density evolution of atoms in the synthetic lattice with the single-site resolution, and observe the nonreciprocal dynamics by controlling the tunneling phase. We show the effect of both the applied phase and the coupling strength between two distinct population regions on the population distribution of atoms in the momentum lattice, and provide the optimal parameters for achieving the nonreciprocal transport.

PLK1 maintains DNA methylation and cell viability by regulating phosphorylation-dependent UHRF1 protein stability.

PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265. Phosphorylation is required for the maintenance of UHRF1 protein stability by recruiting a deubiquitinase USP7. Conversely, PLK1 inhibition decreases UHRF1 protein interaction with USP7 and activates the ubiquitin-proteasome pathway, thereby accelerating UHRF1 protein degradation. UHRF1 degradation decreases the recruitment of DNMT1 to chromatin, and decreases the level of genome-wide DNA methylation, thereby elevating the expression of tumor suppressor genes and decreasing cell viability. We here presented the first report on the novel role of PLK1 in DNA methylation maintenance through UHRF1-DNMT1 pathway, and revealed a novel anticancer mechanism of PLK1 inhibitors.

UHRF1 promotes spindle assembly and chromosome congression by catalyzing EG5 polyubiquitination.

UHRF1 is an epigenetic coordinator bridging DNA methylation and histone modifications. Additionally, UHRF1 regulates DNA replication and cell cycle, and its deletion induces G1/S or G2/M cell cycle arrest. The roles of UHRF1 in the regulation of G2/M transition remain poorly understood. UHRF1 depletion caused chromosome misalignment, thereby inducing cell cycle arrest at mitotic metaphase, and these cells exhibited the defects of spindle geometry, prominently manifested as shorter spindles. Mechanistically, UHRF1 protein directly interacts with EG5, a kinesin motor protein, during mitosis. Furthermore, UHRF1 induced EG5 polyubiquitination at the site of K1034 and further promoted the interaction of EG5 with spindle assembly factor TPX2, thereby ensuring accurate EG5 distribution to the spindles during metaphase. Our study clarifies a novel UHRF1 function as a nuclear protein catalyzing EG5 polyubiquitination for proper spindle architecture and faithful genomic transmission, which is independent of its roles in epigenetic regulation and DNA damage repair inside the nucleus. These findings revealed a previously unknown mechanism of UHRF1 in controlling mitotic spindle architecture and chromosome behavior and provided mechanistic evidence for UHRF1 deletion-mediated G2/M arrest.

AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer.

BACKGROUND: Prostate cancer(PCa) is the most commonly occurring male cancer in the USA. Abiraterone or Enzalutamide have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). However, the treatment-emergent neuroendocrine PCa (t-NEPC) may develop, resulting in drug resistance in about 10-17% CRPC patients. The detailed mechanisms remain unclear.. METHODS: The expression correlation of TOMM20 and AR in PCa was determined by analyzing publicly available datasets, or by IHC staining in tumor specimens. The protein interaction of TOMM20 and AR was validated by co-immunoprecipitation or GST pull-down assay. The impact of TOMM20 depletion on drug sensitivity were elucidated by assays of cell proliferation, invasion, sphere formation, xenograft growth and intravenous metastasis. The intracellular ROS level was measured by flow cytometry, and the NEPC transdifferentiation and characteristics of cancer stem-like cells were validated by RNA-seq, RT-PCR and western blotting. RESULTS: The protein level of TOMM20 is positively correlated with AR in PCa cells and specimens. TOMM20 protein physically interacts with AR. AR antagonists induced the protein degradation of TOMM20 through autophagy-lysosomal pathway, thereby elevating the intracellular ROS level and activating PI3K/AKT signaling pathway. When TOMM20 was depleted, PCa cells underwent EMT, acquired the characteristics of cancer stem-like cells, and developed resistance to AR antagonists. The stable depletion of TOMM20 promoted the transdifferentiation of PCa adenocarcinoma into NEPC and metastasis. Conversely, the rescue of TOMM20 re-sensitized the resistant PCa cells to AR antagonists. CONCLUSIONS: TOMM20 protein degradation induced by AR antagonists promoted the transdifferentiation of PCa to NEPC, thereby revealing a novel molecular mechanism by which AR antagonists develop drug resistance through mitochondrial outer membrane-mediated signaling pathway. These findings suggested that the decreasing or loss of TOMM20 expression in PCa tissues might become a useful predictor of PCa resistance to AR antagonists.

AKT1 regulates UHRF1 protein stability and promotes the resistance to abiraterone in prostate cancer.

Oncogenic activation of PI3K/AKT signaling pathway, together with epigenetic aberrations are the characters of castration-resistant prostate cancer (CRPC). UHRF1 as a key epigenetic regulator, plays a critical role in prostate cancer (PCa) development, and its expression is positively correlated with the degree of malignancy. In this present study we investigated the potential regulatory mechanism of AKT1 on UHRF1, and further validated the in vitro and in vivo anticancer efficacy of AKT phosphorylation inhibitor MK2206 in combination with abiraterone. Both UHRF1 and p-AKT aberrantly overexpressed in the abiraterone-resistant PCa cells. Further studies revealed that AKT1 protein interacts with UHRF1, and AKT1 directly phosphorylates UHRF1 via the site Thr-210. MK2206 induced UHRF1 protein degradation by inhibiting AKT1-induced UHRF1 phosphorylation, and then reduced the interaction between UHRF1 and deubiquitinase USP7, while promoted the interaction between UHRF1 and E3 ubiquitin protein ligase BTRC. MK2206 significantly promoted the sensitivity of abiraterone-refractory PCa cells and xenografts to abiraterone by decreasing UHRF1 protein level, and reversed the phenotype of NEPC, evently induced cellular senescence and cell apoptosis. Altogether, our present study for the first time revealed a novel molecular mechanism of abiraterone resistance through PI3K/AKT-UHRF1 pathway, and provided a novel therapeutic modality by targeting PI3K/AKT1 to promote the drug sensitivity of abiraterone in PCa patients.

Diosgenin inhibits prostate cancer progression by inducing UHRF1 protein degradation.

Prostate cancer (PCa) represents the second cause of cancer death in adult men. Aberrant overexpression of UHRF1 has been reported in several cancer types, and is regarded as a novel drug target for cancer therapy. Nevertheless, no UHRF1-targeted small molecule inhibitor has been testing in clinical trials. Traditional Chinese medicine (TCM) prescriptions have a long history for the treatment of PCa in China, and Chinese herbal extracts are important resources for new drug discovery. In the present study, we first screened the potentially effective components from the commonly used TCMs for PCa treatment in clinic by using network pharmacology together with molecular docking. We identified diosgenin (DSG) as a small molecule natural compound specifically targeting UHRF1 protein. Furthermore, we validated the results by using the wet lab experiments. DSG, by directly binding UHRF1 protein, induced UHRF1 protein degradation through the ubiquitin-proteasome pathway. Importantly, DSG induced UHRF1 protein degradation by reducing the protein interaction with a deubiquitinase USP7. DSG reduced the level of genomic DNA methylation, and elevated the expression of such tumor suppressor genes as p21, p16 and LXN, thereby resulting in cell cycle arrest, cellular senescence and the inhibition of xenograft tumor growth. We here presented the first report that DSG specifically induced UHRF1 protein degradation, thereby revealing a novel anticancer mechanism of DSG. Altogether, this present study provided a promising strategy to discover new molecule-targeted drugs from small-molecule natural products.

Rational design of graphite carbon nitride-decorated zinc oxide nanoarrays on three-dimensional nickel foam for the efficient production of reactive oxygen species through stirring-promoted piezo-photocatalysis.

Stirring-promoted piezo-photocatalysis based on a three-dimensional foam architecture has great potential applications in wastewater treatment and water splitting. However, the detailed mechanism of stirring-promoted piezo-photocatalysis has not been quantitatively studied, and the utilization of visible light needs to be further improved. In this work, the high solar-driven piezo-photocatalytic ability of graphite carbon nitride (g-C3N4)-decorated zinc oxide (ZnO) nanoarrays on nickel (Ni) foam is experimentally achieved and first simulated by the finite element method (FEM). The water flow velocity, depending on the stirring rate, is significantly increased by turbulence-induced fluid eddies while flowing through 3D macropores and nanoarrays, resulting in higher piezoelectricity. Reactive oxygen species (ROS) are experimentally examined by the electron spin resonance (ESR) technique and theoretically calculated by density functional theory (DFT) to confirm the configurations of the heterojunction under photocatalysis and piezo-photocatalysis. In particular, the large enhancement of 1O2 generation suggests the potential of piezo-photocatalysis in biological applications. The mechanism of piezo-photocatalysis is proposed in which the S-scheme heterojunction is realized by piezoelectricity to improve photocatalysis by retaining high redox ability and inhibiting recombination. This work provides a possible approach to harvesting energy sources for piezoelectricity and expands the scope of solar-driven piezo-photocatalysis.

A Systemic Insight into Exohedral Actinides and Endohedral Borospherenes: An&Bm and An@Bn (An=U, Np, Pu; m = 28, 32, 34, 36, 38, 40; n = 36, 38, 40).

A series of exohedral actinide borospherenes, An&Bm, and endohedral borospherenes, An@Bn (An=U, Np, Pu; m = 28, 32, 34, 36, 38, 40; n = 36, 38, 40), have been characterized by density functional theory calculations. The electronic structures, chemical bond topological properties and spectra have been systematically investigated. It was found that An@Bn is more stable than An&Bn in terms of structure and energy, and UB36 in an aqueous solution is the most stable molecular in this research. The IR and UV-vis spectra of An&Bm and An@Bn are computationally predicted to facilitate further experimental investigations. Charge-transfer spectroscopy decomposes the total UV-Vis absorption curve into the contributions of different excitation features, allowing insight into what form of electronic excitation the UV-Vis absorption peak is from the perspective of charge transfer between the An atoms and borospherenes.

Efficient Optical Modulation of Exciton State Population in Monolayer MoS2 at Room Temperature.

The modulation of exciton energy and state density of layer-structured transition metal dichalcogenides (TMDs) is required for diverse optoelectronic device applications. Here, the spontaneous inversion of exciton state population in monolayer MoS2 is observed by turning the pump light power. The excitons prefer to exist in low energy state under low pump power, but reverse under high pump power. To discuss the mechanism in depth, we propose a semiclassical model by combining the rate equation and photo-exciton interaction. Considering the modifying of exciton-exciton annihilation, the spontaneous inversion of exciton state population is phenomenologically described.

Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination.

BACKGROUND: Acute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored. METHODS: Acute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay. RESULTS: Caffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78. CONCLUSION: Caffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.

Observation of photoassociation spectroscopy of 23Na spinor Bose-Einstein condensate.

We report the high-resolution photoassociation (PA) spectroscopy of 23Na excited from the spin-1 Bose-Einstein Condensate (BEC) to the molecular state of 0g-(P3/2)v = 4 and 1g(P3/2)v = 91. By comparing the PA spectra of different spin configurations, we experimentally studied the effect of spin on the PA spectra. The experimental spectra comply well with the theoretical consideration. The results will play an important role in the study of the spin interaction and control of the antiferromagnetism in Na.

Wearable biosensors for real-time sweat analysis and body motion capture based on stretchable fiber-based triboelectric nanogenerators.

Carbon neutrality is a global green energy revolution meaning that the carbon dioxide can make ends meet. However, with the mushroom of the fifth generation wireless systems (5G) and the Internet of Things (IoT), it is a great challenge for powering the ubiquitous distributed devices, because the battery production and high overhead maintenance may bring more carbon emissions. Here, we present wearable biosensors for real-time sweat analysis and body motion capture based on stretchable fiber-based triboelectric nanogenerators (F-TENG). The F-TENG is made of stretchable conductive fiber (Ecoflex coating with polyaniline (PANI)) and varnished wires. Based on the coupling effect of triboelectric effect and enzymatic reaction (surface-triboelectric coupling effect), the wearable biosensors can not only precisely sense the motion states, but also detect glucose, creatinine and lactate acid in sweat in real-time. Importantly, the wearable devices can self-drive without any external power source and the response against glucose, creatinine and lactate acid can be up to 103%, 125% and 38%, respectively. On this basis, applications in biosensing and wireless communication have been demonstrated. This work exhibits a prospective potential application of F-TENG in IoT for diverse use.

Nonlinear laser-induced frequency shift in a 23Na spin-1 condensate.

Herein, we report on the experimental observations and a quantitative determination of the laser-induced frequency shift (LIFS) in the photoassociation (PA) spectra of spinor Bose-Einstein condensate of sodium. Our investigations revealed a nonlinear dependence of the LIFS on the intensity of PA laser. By developing a model within the quadratic Stark effect, we simulate the experimental results via a theoretical model that confirms the former. The experimental observations and the theoretical analysis can further improve the accuracy of investigations on important molecular properties and on preparation of specific molecular states, with possible applications in various key fields.

Morphology engineering of type-II heterojunction nanoarrays for improved sonophotocatalytic capability.

Sonophotocatalysis is one of the most significant outcomes of the exploration of the interaction between piezoelectric field and charge carriers, which exhibits potential applications in dye degradation, water splitting, and sterilization. Although several heterojunction catalysts have been applied to improve the sonophotocatalytic capability, the importance of the morphology on the sonophotocatalytic capability has not been emphasized. In this study, brush-like ZnO nanorod arrays are synthesized on a stainless-steel mesh and subsequently vulcanized into ZnO/ZnS core-shell nanorod arrays to investigate the sonophotocatalytic capability of the heterojunction. The sonophotocatalytic capability increases from 25.1% to 45.4% through vulcanization. Afterward, the ZnO/ZnS nanorods are etched to ZnO/ZnS nanotubes without affecting the crystallography and distribution of the ZnS nanoparticle shell, further improving the capability to 63.3%. The improvement can be ascribed to the coupling effect of the enhanced piezoelectric field and the reduced migration distance, which suppresses the recombination of photoexcited electron-hole pairs while transforming the morphology from nanorod to nanotube, as proven by the electron spin resonance test and numerical simulations. This study explores a novel approach of morphology engineering for enhancing the sonophotocatalytic capability of heterojunction nanoarrays.

Simultaneous measurement of temperature and relative humidity based on a twisted microfiber coated with nanomaterials.

We propose a twisted microfiber interferometer sensor coated with boron nitride (BN) nanosheets for simultaneous measurement of relative humidity (RH) and temperature ($ T $). Sensitive material characteristics (BN nanosheets) enhance refractive index (RI) sensing sensitivity of proposed devices. A twisting process on the microfiber surely improves the evanescent field interaction with the deposited layer. The experimental results show that the RH sensitivities are ${-}{121.6}\;{\rm pm}/\% {\rm RH}$ and 0.26 dBm/%RH for humidity range from 46% to 72% and $ T $ sensitivities of 23.5 pm/°C and ${-}{0.045}\;{\rm dBm}/^\circ {\rm C}$ from 50°C to 90°C. The twisted microfiber interferometer has the advantages of compact structure, high sensitivity, and multiparameter measurement, which has certain potential for more applications.

Actinyl-Carboxylate Complexes [AnO2(COOH) n (H2O) m ]2-n (An = U, Np, Pu, and Am; n = 1-3; m = 0, 2, 4; 2n + m = 6): Electronic Structures, Interaction Features, and the Potential to Adsorbents toward Cs Ion.

Organic compounds of actinyls and their bonding features have attracted extensive attention in nuclear waste separation due to their characteristics of separating fission products. Herein, detailed studies on the binding sites of [AnO2(COOH) n (H2O) m ]2-n (An = U, Np, Pu, and Am; n = 1-3; m = 0, 2, 4; 2n + m = 6) complexes toward Cs are predicted by calculation, and their electronic excitation characteristics were illustrated, providing theoretical supports for the design of Cs adsorbents. The quantum theory of atom in molecules and electron localization function have been implemented to analyze the chemical bonding characterization. The covalent character of An-OC bonds become weaker with increasing COOH- ligands, and the covalent interaction in An-OC bonds is more obvious than that in An-OH bonds. Total and partial population density of state suggest that the 2p orbits of O have more significant contribution in the low-energy region atoms and the 6d/5f orbits of An have more significant contribution in the high-energy region. The Cs+ best adsorption site on [UO2(COOH)2(H2O)2] and [UO2(COOH)3]- is the adjacent oxalates, and the [UO2(COOH)3]- complexes have better adsorption capacity. Besides, the electronic excitation characteristics of Cs+ adsorption on the UO2(COOH)2(H2O)2 complex were analyzed by the UV-vis spectrum and hole-electron distribution.

Fast response microfiber-optic pH sensor based on a polyaniline sensing layer.

The microfiber-optic interferential sensor based on polyaniline (PANI) sensing layer is efficiently performed in pH detection. The refractive index changes of PANI film can be translated into a significant wavelength shift in the interferometric fringe. We demonstrate the feasibility of PANI attached to the fiber surface in studying the interface polymerization method. The sensing performances of an improved sensitivity in acid solution with -0.54nm/pH and alkaline solution with 0.28 nm/pH are systematically investigated. By taking advantage of its miniature size and mechanical flexibility, the microfiber interferential sensor might make a promising platform for pH measurement.