Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Objective: This study aims to elucidate the role of aryl hydrocarbon receptor nuclear transporter 2 (ARNT2) in cervical cancer (CC) and explore the potential mechanism by which ARNT2 promotes the progression of CC through the protein phosphatase 2A (PP2A)/Akt signaling pathway. Methods: Bioinformatics tools were used to analyze the expression level of ARNT2 in cancer and its correlation with cancer prognosis. Western Blot and immunohistochemistry staining were used to detect the expression of ARNT2 protein in CC tissues and cells. ARNT2 was knocked down in SiHa and HeLa cells, respectively. Cell Counting Kit-8 assay and colony formation assay were used to detect changes in cell proliferation. Transwell assay and plate scratch assay were used to detect changes in cell migration and invasion. Western Blot assay was used to detect changes in the expression of PP2A/Akt signaling pathway after ARNT2 expression was downregulated. Finally, a CC xenograft tumor model was constructed to evaluate the effect of ARNT2 on SiHa cell tumorigenesis in vivo. Results: ARNT2 is highly expressed in tumor tissues and cell lines. ARNT2 knockdown can significantly inhibit the proliferation, invasion and migration of SiHa and HeLa cells in vitro and in xenograft models. Further studies have shown that ARNT2 may promote tumor formation by regulating the PP2A/Akt pathway. Conclusion ARNT2 promotes the malignant biological behavior of CC cells through the PP2A/Akt signaling pathway, confirming its potential as a prognostic marker for CC.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

Talents are the main force for the development of traditional Chinese medicine（TCM）， and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present， we are still exploring and developing in the fields of the formulation， implementation and evaluation indicators of TCM talent evaluation system. However， there are shortcomings and difficulties. For instance， insufficient stratification in the evaluation， excessive emphasis on the quantity of achievements， neglecting the quality of the achievements and the actual contribution， imperfect assessment indicators， and the weak characteristics of TCM. Therefore， national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard， in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value， ability and contribution. For the evaluation of TCM clinical talents， China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM（CCCL-TCM）， which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry， and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.

Objective: To investigate the safety and efficacy of 125I radioactive seed implantation in the treatment of mediastinal lymph node metastasis. Methods: Records of 53 patients enrolled in Shaanxi Provincial Tumor Hospital from June 2014 to June 2018 with me-diastinal lymph node metastasis treated by computed tomography (CT)-guided 125I seed implantation were analyzed retrospectively. The preoperative treatment planning system was validated after the surgery. Intraoperative and post-operative complications were re-corded. The improvement in quality of life was observed. Chest CT follow-up was conducted 1 month, 3 months, 6 months, 1 year, and 2 years after treatment. The local focus control was evaluated. The median survival and total survival were recorded, and the survival prognosis and causes of death were analyzed. Results: The median survival time was 254 days (8.5 months), one-year survival rate was 48.67%, and complete and partial response rate was 83.02% (44/53). Multivariate Cox model analysis showed that the survival progno-sis was related to the Eastern Cooperative Oncology Group (ECOG) score, distant metastasis at the time of implantation, concurrent chemotherapy after implantation, and secondary seed implantation (P<0.05). The rates of developing pneumothorax and hemoptysis during and after the surgery were 20.75% (11/55) and 13.20% (7/55), respectively. No patients died. After implantation, the remission rate of cough, shortness of breath, pain, hoarseness, and superior vena cava syndrome was 60.00%-82.61%. Conclusions: CT-guid-ed 125I seed implantation in the treatment of mediastinal lymph node metastasis has the advantages of minimal trauma, remarkable cu-rative effect, safety, and feasibility. It has important application value and is worthy of further clinical application.

"Belt and Road" is not only a concept of space and international economic cooperation strategy,but also a China oriented culture framework in the area of globalization.The implementation of "Belt and Road Initiative" strategy needs to put culture first,while traditional Chinese medicine (TCM) culture is an important starting point to boost the "Belt and Road" construction.TCM culture communication with countries along "Belt and Road" should take strategies of overall communication,local communication and differentiation communication.And it also needs to promote the construction of TCM communication platform,to enrich TCM culture connotation,to build TCM culture brand and develop cultural and creative industries in TCM.

BACKGROUND: Using the rapid growth period of the chorioallantoic membrane from the 8th day to the 12th day, vascular growth at bone defect end and vascular implantation of a bone graft substitute into the human body can be simulated.OBJECTIVE: To load hydroxyapatite into a chick embryo chorioallantoic membrane model, and to establish an implanted revascularization model.METHODS: Twelve rosette eggs were incubated under the same suitable conditions for 8 days. After windowing, the eggs were randomly divided into two groups: experimental group was implanted with hydroxyapatite material to establish the model of chick embryo chorioallantoic membrane carrying hydroxyapatite; control group was implanted with filter paper material, sealed and placed into a constant temperature and humidity box to continue to hatch. At the 12th day of incubation, length of new vessels and length of new vessels per unit area in the two groups were observed, and the angiogenesis on the hydroxyapatite and filter paper was observed.RESULTS AND CONCLUSION: The mean length of new vessels and length of new vessels per unit area were 24.031 mm and 0.242 mm/mm2 in the experimental group, and 23.561 mm and 0.212 mm/mm2 in the control group, respectively. There were no significant differences between two groups. Additionally, vascular tissues were obviously observed on the hydroxyapatite samples in the experimental group. These experimental results show that the establishment of the model of chick embryo chorioallantoic membrane carrying hydroxyapatite provides a simple and accurate in vitro animal model for studies on ideal bone graft materials and angiogenesis. The hydroxyapatite has no effect on the angiogenesis on the chorioallantoic membrane.

The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6) from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein (Sdo1p) from yeast. Our data show that Sdo1p interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2:2 dimer. Structural analysis indicates that Sdo1p bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdo1p on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdo1p in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a conformational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdo1p, and Efl1p, which interrogates the functional P-site to control the departure of the anti-association factor eIF6.
Crystallography, X-Ray ; GTP Phosphohydrolases ; chemistry ; metabolism ; Humans ; Protein Domains ; Ribosome Subunits, Large, Eukaryotic ; chemistry ; metabolism ; Saccharomyces cerevisiae ; chemistry ; metabolism ; Saccharomyces cerevisiae Proteins ; chemistry ; metabolism

The in vivo assembly of ribosomal subunits is a highly complex process, with a tight coordination between protein assembly and rRNA maturation events, such as folding and processing of rRNA precursors, as well as modifications of selected bases. In the cell, a large number of factors are required to ensure the efficiency and fidelity of subunit production. Here we characterize the immature 30S subunits accumulated in a factor-null Escherichia coli strain (∆rsgA∆rbfA). The immature 30S subunits isolated with varying salt concentrations in the buffer system show interesting differences on both protein composition and structure. Specifically, intermediates derived under the two contrasting salt conditions (high and low) likely reflect two distinctive assembly stages, the relatively early and late stages of the 3' domain assembly, respectively. Detailed structural analysis demonstrates a mechanistic coupling between the maturation of the 5' end of the 17S rRNA and the assembly of the 30S head domain, and attributes a unique role of S5 in coordinating these two events. Furthermore, our structural results likely reveal the location of the unprocessed terminal sequences of the 17S rRNA, and suggest that the maturation events of the 17S rRNA could be employed as quality control mechanisms on subunit production and protein translation.
Cryoelectron Microscopy ; Escherichia coli ; metabolism ; Escherichia coli Proteins ; genetics ; metabolism ; GTP Phosphohydrolases ; genetics ; metabolism ; Mass Spectrometry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Ribosomal ; analysis ; metabolism ; Ribosomal Proteins ; chemistry ; genetics ; metabolism ; Ribosome Subunits, Small, Bacterial ; chemistry ; metabolism ; ultrastructure ; Salts ; chemistry