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Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5' UTR of mRNA.

Berberine is a commonly used traditional Chinese medicine, which has the antimicrobial and anti-inflammatory properties. Ongoing investigations have identified berberine as an effective medicine for systemic diseases, such as cardiovascular diseases, diabetes mellitus and neurological disorders. At the same time, there exists a close relationship between oral microbiota and these systemic diseases. This review focuses on the relationship between berberine, oral microbiota and systemic diseases, offering new insights for the treatment of systemic diseases.

With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi‐1 co‐localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1‐driven Bmi‐1 knockout in bone‐marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1‐driven Bmi‐1 overexpression showed a contrasting phenotype to Prx1‐driven Bmi‐1 knockout in BMSCs. Regarding mechanism, Bmi‐1‐RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi‐1‐EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region −1605 to −1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1‐driven Bmi‐1 overexpression rescued the SOP induced by Prx1‐driven Bmi‐1 knockout in BMSCs. Thus, Bmi‐1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1‐driven Bmi‐1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP. [ABSTRACT FROM AUTHOR]

This study focuses on what latecomers can leverage to drive their learning; moreover, it examines how domestic customer demands and latecomers' internal capabilities affect their preferences for external technology acquisition. Using a policy-capturing technique, this study shows that customer demand and latecomers' absorptive capacity are positively related to their preferences for technology purchase and imitation. R&D capabilities negatively affect latecomers' preferences for technology purchase. Furthermore, customer demand allows latecomers to prefer technology purchase over technology imitation; absorptive capacity drives latecomer preferences for technology imitation over technology purchase; and latecomers with high R&D capabilities are more inclined to 'NOT purchase' rather than 'NOT imitation'. [ABSTRACT FROM AUTHOR]

In this paper, the structure, hydrogen storage capacity, mechanical, electronic, optical and thermodynamic properties of hydride perovskites KCuH 3 and RbCuH 3 are systematically studied via using density functional theory (DFT) for the first time. The formation energies and mechanical properties of XCuH 3 (X = K, Rb) hydrides indicate that KCuH 3 and RbCuH 3 are both thermodynamically and mechanically stable. The values of Pugh's index and Cauchy pressure for KCuH 3 and RbCuH 3 indicate that they are both brittle materials. In addition, their bonding types are mainly ionic bonds. Electronic properties show that these compounds are metallic. The hydrogen storage capacities of KCuH 3 and RbCuH 3 are calculated to be 2.78 wt% and 1.95 wt%, respectively. The optical properties indicate that KCuH 3 and RbCuH 3 both have high dielectric functions in the visible range and their absorption coefficient peak in the ultraviolet range. Additionally, the thermodynamic properties, including free energy, Debye temperature, melting temperature, entropy and heat capacity are calculated. The analyzed physical properties of KCuH 3 and RbCuH 3 perovskite hydrides suggest that they have great prospect in hydrogen applications. All the above parameters are calculated for the first time, which could contribute significantly to the development of sustainable energy technologies. • XCuH 3 (X = K, Rb) perovskite have been investigated using the first principles. • XCuH 3 perovskite exhibit thermodynamic and mechanical stability. • The gravimetric hydrogen storage capacity is found to be 2.78 wt% for KCuH 3. [ABSTRACT FROM AUTHOR]