Abstract:Mitochondria is an major organelle for cellular physiology and metabolism. The homeostasis of mitochondrial biogenesis and degradation is important in maintaining the stability of energy metabolism. Mitophagy is regulated by PINK1/Parkin and LC3 signaling. Parkin, as an E3 ubiquitin ligase, mediates the process of mitochondrial degradation. Parkin is also involved in many other intracellular metabolic activities, such as regulating mitochondrial associated membrane (MAM) and controlling calcium flow in-between organelles. In response to external stimuli like chronic cold exposure, with abundant mitochondria biogenesis, beige adipocytes are generated in the white adipose tissue. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype. Beige adipocyte is an ideal model to study the mechanism of mitochondrial regulation. However, the regulatory mechanism of mitochondrial homeostasis is still unclear. We have reviewed recent studies of novel mechanism on Parkin-mediated mitophagy, and furthermore, the regulatory mechanisms of organelle contacts between mitochondria, endoplasmic reticulum and lysosome.

Abstract:Living organisms are in threats of endogenous/exogenous DNA damages. DNA damage impedes both replication and transcription accuracy. To ensure correct replication and transcriptions, and subsequent genome integrity and genetic stability, living organisms have evolved different mechanisms for DNA repair. This review focused on RNA polymerase surveilled (RNAP-S) mechanisms for DNA repairs, and discussed biological significance of the RNAP-S repairs and perspectives. RNA polymerase (RNAP) structure is a complex, being composed of many subunits with different roles in RNAP function. RNAPII has a trigger loop (TL) and a bridge helix (BH), these domains sense DNA lesions during transcription. RNAP stalls at the DNA damage sites to avoid transcribing mutated mRNA, allowing the repair system to be recruited. Interestingly, Mfd and DksA dissociate the stalled RNAP while UvrD pulls back the stalled RNAP on the template DNA to expose the lesions for subsequent performance of lesion repairs. Similarly, the CSB protein, its ubiquitination and OGG1 mediate RNAP-S repairs in eukaryotic cells. Most recently, it has been shown that RNAPIII is involved in homologous recombination repair.

Abstract:Cell-to-cell communication is essential for the organization, coordination and development of multi-cellular systems. Intercellular communication and substance exchange are important links in the development, tissue repair and cell survival of multicellular organisms. Recently, it has been found that tunneling nanotubes (TNTs) connections are formed between cells for long-distance communication. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood. It has been shown to include that there are considerable differences in the structure, formation process and functional properties of TNTs in cells of different types. Recent progress has been made in this new research field. However, the exact role of TNTs for intercellular communication and their impact on diseases are still uncertain, further research is urgently needed. The combined data from numerous laboratories indicate that some TNTs mediate a long-range communication to coordinate metabolism and signaling. This paper aims to describe the structure, morphology, characteristics and function of TNTs, the formation mechanism of TNTs and the application prospect of TNTs in disease transmission and disease treatment, and discusses the research advances of TNTs-mediated electrical coupling.

Abstract:Osteoarthritis (OA), as the most common degenerative joint disease, is mainly characterized by destruction and degradation of cartilage, which leads to joint function loss and seriously affects the quality of life of patients. More and more evidences show that in addition to cartilage tissue, the pathological changes of OA involve other tissue system including synovium, bone and subchondral bone. Among that, synovium, an important part of the tissue system, plays an increasingly prominent role in OA. Synovial cells are classified into type A synovial macrophage (SM) and type B synovial fibroblast (FLS), which play different but closely related roles in OA. This article reviews the role of different types of synovial cells in OA, and provides scientific theoretical basis for further understanding the pathogenesis and treatment of OA.

Abstract:Up to now, the COVID-19 is still prevalent in many countries around the world, and threatens health security of global public seriously. China not only developed the reagent kits for detecting of SARS-CoV-2 nucleic acids and testing equipment, but also established 10 in 1 mixed detection strategy and related policies which have improved the efficiency of epidemic prevention and control, and ensured the health of the people. This review summarizes the principles, advantages, disadvantages and supporting equipment of various methods for the detection of SARS-CoV-2.

Abstract:Super-resolution microscopy (SRM) can bypass the optical diffraction limitation to imaging resolution and visualize previously unobservable nanoscale structures. This significant breakthrough has promoted the progress and development of modern life science and biomedical research. Cell is the basic unit of living organisms, and studying the fine structures and dynamic processes inside living cells is an indispensable way to grasp the essence of life. However, due to the limitations of imaging principles or conditions, the applications of early SRM technologies in live cell imaging were limited in different degrees. In recent years, with the development of SRM technology and related technologies, the application of SRM in live cell imaging research has also been increasingly developed. This paper briefly introduces the basic principles and characteristics of several common SRM technologies, and on this basis, focuses on the latest research progress and development trend in their live-cell-imaging applications. For STORM, the developments of high-density localization algorithms and new blinking fluorescent probes promote its application in live cell super-resolution imaging, realizing the monitoring of the distribution and changes of specific proteins in the nucleus of living cells, as well as the super-resolution imaging of the dynamic process of organelle membranes in living cells. For STED, the developments of new fluorescent probes with high photostability, good bleaching resistance and low saturation threshold, and the utilization of new methods such as time-gated technology for reducing the depletion power help with its application in live cell imaging. The long-term super-resolution monitoring of the dynamic process of specific organelles in living cells and the super-resolution imaging of the interactions between different organelles in living cells are realized. For SIM, by introducing ingenious methods such as TIRF illumination, pattern activation and grazing incidence, researchers try to improve its resolution while retaining its advantage of live cell imaging, and realize the dynamic super-resolution imaging within 100 nm scale and with fast imaging speed in living cells.

Abstract:Vision plays an important role in living and learning for human, and its formation includes three processes: retinal photoelectric conversion, optic nerve transmission, and visual cortex perception. According to statistics, there are more than 450 million people with various vision problems in the world. Visual impairment like blindness will significantly reduce the quality of human life. Visually impaired patients usually have no or weak vision due to a problem in one of the processes, which provides possibilities to recover part of the vision of with the help of artificial visual aid systems for most visually impaired patients. This article reviews the development status, limitations and outlooks of state-of-the-art various artificial visual aid systems. To date, there are three kinds of visual aid systems for different vision impairment situations. For patients with retinopathy or lesions in lens, vitreous, cornea, etc., the remaining part of the visual pathway is still functional, so the electrode array or photoelectric array can be implanted into the retinal area, and plays a role in retina to generate electric signals to stimulate the optic nerve, which transmits electrical signals with visual information to the brain. For visually impaired patients whose visual cortex is functional normally, the electrode array can also be applied to the brain's visual cortex to input electrical signals with visual information directly. In addition, external devices using artificial intelligence to convert vision into voice commands, tactile array coding, etc., can help blind patients obtain environmental information. The implantable visual aid systems mainly face the risk of biological rejection and infection, and their resolution of vision restoration is limited by the electrode size. More complete visual aid electronic devices and systems that can be worn or implanted need to be developed to benefit a large number of patients with visual dysfunction. As a result, here new ideas for implanting devices and extracorporeal aid system are proposed to provide some valuable references for this field.

Abstract:The formation of plaques by the deposition of amyloid-β (Aβ) in the brain is a hallmark of Alzheimer’s disease (AD). Transgenic mouse models based on amyloid-β precursor protein (AβPP) exhibited accelerated plaque formation and memory impairment. However, in some models, the correlation between memory loss and plaque formation is poor. Our lab has recently found a strong correlation between formaldehyde levels and cognitive impairment in AD patients and animal models. In the present study, we found that working memory was inversely correlated with formaldehyde levels in AβPP^Lon/Swe transgenic mice, which showed memory deficiency at 3 months of age but normal memory at 6 months. Impaired memory in 3-month-old mice was accompanied by higher levels of formaldehyde and hyperphosphorylated tau than controls. Administration of resveratrol, which is a formaldehyde scavenger, rescued the cognitive deficits in these mice by reducing formaldehyde levels and attenuating tau hyperphosphorylation. With increased expression of formaldehyde catalytic enzymes such as aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase III (ADH3), 6-month-old AβPP^Lon/Swe mice displayed similar levels of formaldehyde and working memory as controls. We discovered that brain formaldehyde levels were significantly associated with the progression of memory deficit in AβPP^Lon/Swe transgenic mice, and that recovery of memory was associated with formaldehyde reduction. Our findings provide valuable insights into the underlying mechanisms of AD.

Abstract:Vaginal microflora pathological image is an important basis for the diagnosis of bacterial vaginosis, but analysis of the images manually takes a lot of time and effort, leading to low diagnosis efficiency, so new methods of automatic pathological image diagnosis need to be sought. In this paper, we proposed a model, ResLab, to diagnose vaginal microflora pathological image automatically. It took the pathological reports of gynecological examination as training set, and used deep learning technology to perform end-to-end analysis on the pathological images. The ResLab model predicted Nugent score to assist doctors in grading diagnosis. We optimized the ResLab in multiple ways to improve the prediction accuracy, by increasing the number of layers to extract deeper features, stacking two small convolution kernels to increase the receptive field, removing ReLU layers to reduce complexity, and replacing average pooling layer with max pooling layer to extract the most salient feature. It was proven that each optimization plan can significantly improve the perfomance of the model. The prediction accuracy of the ResLab model reached 82.19%, which outperformed VGG, GoogLeNet, ResNet. The ResLab model can provide doctors with relatively accurate reference results, thereby improving diagnosis efficiency and reducing diagnostic error.

Abstract:Fluorescence lifetime is the average amount time a fluorophore spends in excited state before returning to the ground state. In this paper, methods for quantifying intra- and inter-molecular interactions based on fluorescence lifetime measurement were developed. One is quantification of DNA secondary structures formation by fluorescence lifetime change through G-base quenching, and the other is quantification of inter-molecular interactions by fluorescence lifetime change through fluorescence resonance energy transfer (FRET). The first method cleverly utilizes the properties of G-base to quench adjacent dye molecules, and combines with changes in fluorescence lifetime, to determine the formation of DNA secondary structure and the formation ratio. FRET is an important means for studying biological molecular interactions. Traditional FRET methods are mainly based on change in intensity, but this change is susceptible to changes in fluorescence expression levels, molecular diffusion in samples and crosstalk between fluorophores, which brings complexity in experimental design and poor repeatability of experimental data. FRET measurement based on fluorescence lifetime can overcome the disadvantages mentioned above. By detecting changes in the fluorescence lifetime of the donor, we can quickly and easily determine whether FRET occurs, and through establishing a systematic data analysis method we can get FRET efficiency and information about inter-molecular interactions.

Abstract:The fission and fusion of mitochondria is the main way of dynamic changes of mitochondrial membrane, and it is also an important means to maintain the normal function of mitochondria. The mechanism of mitochondrial fission used to be based on fluorescent-labeled optical microscopy imaging. Due to the limitation of resolution, it is not possible to directly observe the ultrastructural characteristics of the mitochondrial fission. Cryo-electron tomography (cryo-ET) obtains more realistic structural information by maintaining the physiological state of the sample as much as possible. In this article, we use cryo-ET to study the membrane dynamic of mitochondrial fission in primary hippocampal neurons. By imaging the spontaneous mitochondrial fission, we found that both central and peripheral mitochondrial fission have contact with the endoplasmic reticulum (ER). It is worth noting that we have also found that some mitochondria will separate the outer mitochondrial membrane from the inner membrane, forming a "matrix-free" area. All these may show a way of mitochondrial quality control.