Abstract:The 2021 Nobel Prize in Physiology or Medicine is awarded to American physiologist David Julius and molecular biologist Ardem Patapoutian for their groundbreaking discoveries of receptors for temperature and touch. The ability to perceive external stimuli, such as hot and cold sensation and mechanical pressure, is crucial to our adaptation to the ever-changing environment, protecting us from harm. Prior to the discoveries of this year’s laureates, how temperature and mechanical stimuli are perceived and converted into electrical pulses was unknown. Unveiling of the temperature receptor TRPV1 and the touch receptors PIEZOs led to a thorough understanding of this process, also revealing more members of the TRP receptor family and PIEZO receptor family, furthermore encouraging scientists to research on its mechanisms and functions, pointing towards innovative treatment methods for tackling pain at the root. This article summarizes the discovery process, structure and mechanisms of these two receptors and also introduces illnesses caused by receptor mutations, shining light on their role as potential targets for drug development.

Abstract:The 2021 Nobel Prize in physiology or medicine was awarded to David Julius and Ardem Patapoutian, based on the outstanding contributions in temperature receptors TRPV1 and tactile receptors PIEZO1/PIEZO2, respectively. They elucidated the mechanisms underlying how the human nervous system senses cold/heat and mechanical stimulation, which contributes to the development of drugs for long-term pain. This article reviews David Julius’ pioneering work on TRPV1 which can be activated by capsaicin, heat (>43℃), H⁺ (pH<6.0), and the critical roles of TRPV1 participating in cancer pain, chronic inflammatory pain, neuropathic pain, and visceral pain by inducing peripheral and/or central sensitization.

Abstract:Human have several senses, including vision, touch, hearing, taste, smell and taste, as well as temperature and pain. How organisms perceive the physical world has always attracted people to explore. Although new breakthroughs have been made in the discovery and research of different sensory receptors, the underlying molecular and cellular mechanisms of these sensation remain elusive. The 2021 Nobel Prize in physiology or medicine was awarded to David Julius and Ardem Patapoutian for their profound contributions to the discovery of temperature sensing and tactile receptors. For hearing research, although it won the Nobel Prize as early as 1961, the research on hearing receptors is still insufficient. This article review focuses on the discovery and research process of touch and hearing receptor NOMPC in invertebrate and hearing receptor TMC in mammalian. And this review also provides suggestions for the development of sensory perception in the future.

Abstract:Microglia mainly control the immune efficiency of the central nervous system and play an important role in various psychiatric diseases. Neuroinflammation triggered by the signaling pathway activation is related to the development of depression. Microglia are the main mediators of neuroinflammation. Different stimulations promote the polarization of microglia, which secrete inflammatory cytokines that affect the regulation of neuroinflammation. Clinical and experimental research in vivo and in vitro have demonstrated the relationship of depression with neuroinflammation mediated by microglial polarization. The possible mechanisms of polarization mediating depression involve NF-κB signaling pathway activation, respiratory bursts, complement receptor 3 (CR3) signaling pathway activation, NLRP3 inflammation activation, cannibalism receptor 1 (CB1) activation, Notch-1 signal pathway stimulation, and PPARγ receptor activation. This review discusses research progress on the relationship between microglial polarization and depression.

Abstract:Depression is one of the world’s serious health problems with high prevalence, high disability and high recurrence rate, and places a great burden on society. The newly discovered CREB-regulated transcription coactivator 1 (CRTC1) is highly expressed in the brain, especially in hippocampal neurons, and plays an important role in dendrite growth, long-term synaptic plasticity and behavior. Since Crtc1 knockout (Crtc1^-/-) mice were first successfully prepared in 2012 and Crtc1^-/- mice exhibited a depression-like behavioral phenotype, the growing clues suggest that CRTC1 is involved in depression. Our previous work demonstrates that knockdown of CRTC1 in hippocampal dentate gyrus directly induced depression-like behavior in mice. Downregulation of CRTC1 expression in hippocampus is associated with depression-like behaviors in CUMS (chronic unpredictabk mild stress), CSDS (chronic social defeat stress) and CRS (chronic restrain stress) mouse models, LPS(lipopolysaccharide)-treated mouse model and prenatal stress-induced depression model in offspring rats. Furthermore, abnormal CRTC1 expression or activation may be involved in depression-like behavior via SIK2/CRTC1/CREB/BDNF pathway, CRTC1/BDNF/TrkB/VGF pathway, agmatinergic system and neuroinflammation. In addition, Crtc1^-/- mice are shown to be resistant to the antidepressant effects of the tricyclic antidepressants such as fluoxetine, desipramine, venlafaxine and imipramine etc., suggesting that CRTC1 alterations may be related with treatment-resistant depression. Histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) partially rescues the depression-like behavior of Crtc1^-/- mice accompanied by an increased expression of BDNF, the effects are mediated by CRTC1. Although CRTC1 expression is disturbed in the brain of depression-related models, whether and how it is involved in the process of neurogenesis and neuroplasticity impairments in depression still needs further research. This article reviews the research of CRTC1 in depression from the aspects of behavior, related signal pathways and participation in the role of antidepressants.

Abstract:Depression is a kind of mental disorder with high prevalence rate, easy relapse and high suicide rate, which can easily lead to cognitive impairment and other problems. Phototherapy, with its advantages of noninvasive, less side effects and quick curative effect, has attracted wide attention, which provides a new possibility for regulating the biorhythm and sleep disorders of depression. Light signals are projected through retinal ganglion cells to depressed brain areas to participate in non-visual imaging functions, activating nerve cell activity, secreting neurotransmitters to induce physiological changes in neural pathways, and regulating circadian rhythms, mood, and sleep in the biological organism to improve depressive behavior. The most common forms of light therapy include bright light therapy, blue light therapy and near infrared light therapy. The choice and use of different light sources can have different effects on the therapeutic outcome, and their wavelength, dose and optimal mode of action are closely related to the therapeutic outcome. The results also suggest that the use of low intensity beneficial wavelengths of blue light can have the same antidepressant effect as high intensity bright light therapy, but the best mode of application of phototherapy is still controversial. In order to promote the application of phototherapy in the field of life science and clinical practice, a large number of studies on optical parameters in clinical and animal models are still needed. This paper will summarize the current therapeutic targets of light therapy in depression-related brain regions and downstream neural circuits, explore the mechanisms of action of different spectra and their therapeutic parameters, discover the advantages of their light sources and suitable therapeutic parameters, and propose the problems of phototherapy, such as the optimal light parameters, the universality of different populations, and the safety issues arising from unsuitable light sources, which are still to be solved. As phototherapy continues to be explored in depth, the selection of optimal phototherapy pathways, the screening of optimal light parameters, and the combination of other classical therapeutic methods will provide references for experimental studies and clinical applications of phototherapy against depression and produce breakthroughs in the treatment of depression.

Abstract:Depression is a significant and persistent mood or low state of mind as the main performance of mental illness. Light therapy has attracted more and more attention due to its low side effects and low cost. Light therapy is a physical therapy method that uses artificial or natural light to prevent and cure diseases by using light of different duration and intensity. Animal and clinical trials have shown that light therapy can effectively relieve depressive symptoms. However, the neural mechanism of the antidepressant effect of light therapy is still not fully understood, and the application paradigm of light therapy is still controversial. This paper briefly introduces the clinical application light therapy in the seasonal depressive disorder (SDD), bipolar disorder (BD), sub-threshold depression (SD), major depressive disorder (MDD), perinatal depression (PPD), post stroke depression (PSD), and the underlying mechanisms of those effects of light therapy in anti-depression. Animal studies reveal that the effects of light on mood via intrinsically photosensitive retinal ganglion cells to perihabenular nucleus (ipRGC-PHb) pathway. A recent report demonstrated that activation of the disynaptic retina-vLGN/IGL-LHb pathway underlies the anti-depressive effects of light therapy. Monoamine neurotransmitter as well as cortisol are also involved in regulating depressive-like behaviors during light therapy. The current review provides potentially theoretical basis for the optimization and promotion of light therapy in anti-depression.

Abstract:Calcium homeostasis modulator 2 (Calhm2) is involved in the modulation of Ca²⁺ activity and ATP release. Our previous work has demonstrated that Calhm2 plays a crucial role in the progression of depression by regulating the astrocytic ATP release. In order to further explore the role and mechanism of Calhm2 in the development of depression, we firstly predicted the ATP binding site (glutamine, amino acid 87) of Calhm2, and established a mouse line that carried calhm2 mutation by mutating the glutamine to alanine (Q87A). Secondly, by using the primary culture of astrocyte and ATP detection analysis, we found that Calhm2 Q87A mutation resulted in a significant decrease of ATP release in astrocytes. Furthermore, we found that the ATP release decreased in hippocampal slice from Calhm2 Q87A mutated mice. Importantly, Calhm2 Q87A mutated mice showed a higher susceptibility to develop depression-like symptoms than that of wild type mice when exposed to chronic unpredictable mild stress (CUMS). Taken together, we identified that Q87 site is important for Calhm2-mediated ATP release in astrocytes and this point mutation of Calhm2 promotes depression susceptibility induced by stress in mice. The present work further defines the molecular mechanism of Calhm2 in the development of depression, with the implication of a potential avenues for the diagnosis and therapeutics of depression-related diseases.

Abstract:Telomeres localize at the ends of all linear chromosomes of eukaryotic cells to preserve genome integrity and cell survival. The highly repetitive telomeric sequences can easily fold into specific secondary structures that are difficult to replicate, resulting in increased replication stress. Telomeric repeats are bound by Shelterin complex, which consist of six telomere-specific proteins, and function to protect telomeres by preventing aberrant DNA damage response activation. Recently, it was shown that Shelterin components can also regulate the choice of DNA repair pathways in dysfunctional telomeres, and participate in telomere replication. In this review, we summarize how the secondary structures in telomere are stabilized/removed by Shelterin to ensure repilication proceeding. Moreover, we also discussed the inhibition of DNA repair at telomeres by Shelterin and how Shelterin mediates the repair pathway choice of dysfunctional telomeres. There is still much room to explore on the coordination between telomere protection, replication and regulation of telomeric DNA repair. Hopefully, the further exploration of telomere maintenance mechanism can provide new ideas and therapeutic strategies for telomere-related diseases such as aging and cancer.

Abstract:Affected by the pregnancy cycle, the mammary gland undergoes cyclical developmental changes of pregnancy-lactation-involution in the life of female mammals. In the transition of mammary gland from involution to lactation, the mammary gland cells undergo apoptosis and renewal to reach the self-renewal and self-repair of mammary gland, which is defined as mammary gland remodeling. The mammary gland undergoes significant changes in morphology during mammary gland remodeling, and this process varies across species. In rodents, the involution is divided into two phases based on the reversal of phase. The first phase (first 48 h after weaning) is characterized by milk stasis and lysosomal content release into the cytosol and extensive cell death. The second irreversible phase (after 48 h of weaning) facilitates the remodeling of mammary gland. Compared with rodents, the remodeling process of the mammary glands in dairy livestock exhibits a regenerative involution to maintain subsequent lactation. During the regenerative involution, the regress of mammary gland cells is not significant and the mammary alveolar structure remains basically intact. Alveolar structure is heterogeneous and only shows a few alveolar collapses, and the number of apoptotic bodies only slightly increases. The regenerative remodeling of mammary gland is of great significance to the mammary health and maintenance of the next cycle of lactation in dairy livestock. If the dry period of dairy cows is shortened, the milk production in the next cycle will be significantly reduced. The hormones level, proteases, cytokines and oxidative stress have influences on the remodeling of mammary gland through the various cellular signal pathways. Beyond the internal factors, dietary nutrition and various environmental factors, including heat stress and photoperiod, play important roles in regulating the process of remodeling of mammary gland. The current review summarizes the studies on mammary gland remodeling in recent years, and highlights the factors (including hormones, proteases, cytokines, etc.) regulating the regenerative involution in the mammary gland of dairy livestock. This review tries to uncover the internal mechanism of mammary gland remodeling and provides scientific basis to regulate it.

Abstract:Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this kind of virus is highly infectious. Patients will experience severe acute respiratory infection symptoms if they are infected by the virus. Unfortunately, some patients have a very bleak prognosis or even die of it. Therefore, it seriously affects people’s normal life. Nowadays, various countries are actively conducting relevant research and have conducted in-depth discussions on the response plan to be adopted after the outbreak of COVID-19. This review includes not only the pathogenic characteristics, pathogenic mechanism and detection methods of SARS-CoV-2, but also the treatment and prevention of COVID-19.

Abstract:With the rapid progress of terahertz generation and detection technology, the application of terahertz technology has developed quickly and extended to broad fields. Especially in biomedicine, terahertz technology shows its potential in biological intervention and disease treatment. In this paper, firstly, we gave a brief introduction about terahertz radiation, its characteristics and the classifications of its generation. Terahertz radiation has the potential to non-destructively modulate the functions of living organisms because of its low energy and non-ionizing radiation characteristics, which do not cause damage to organisms. Then, we illustrated two common biological effects induced by terahertz radiation: thermal effects and non-thermal effects. Thermal effects are more likely to cause thermal damage to cells through increased temperature, whereas non-thermal effects do not cause obvious macroscopic temperature changes, but causes changes in genetic level and cellular morphological functions through other ways. Finally, on both cellular and organismic levels, we gave a detailed review of the biological effects induced by terahertz radiation on different cell types and its alteration in cell signaling. Different kinds of cells and organisms have diverse sensitivity to terahertz radiation, and the differences between the various radiation scenarios should be taken into full consideration when constructing the safety criteria. Meanwhile, the interaction mechanisms between terahertz waves and biological macromolecules need to be further investigated, and the specific signaling pathways and gene regulation of the biological effects of terahertz radiation need to be clarified. Thus, the similarities and differences in the mechanisms of terahertz action on biological organisms under different radiation conditions can be distinguished. We believe that this review will be beneficial to researchers engaged in the field of terahertz technology and biological applications.

Abstract:Mitochondria play a pivotal role in innate immunity. Specifically, mitochondria can trigger innate immune response by releasing various damage associated molecular patterns (DAMPs), such as mitochondrial DNA (mtDNA), mitochondrial transcription factor A (TFAM), mitochondrial N-formyl peptides (F-MITs). However, the virus also uses a corresponding mechanism to suppress the innate immunity induced by mitochondrial DAMPs. It is well known that moderate exercise has a positive and healthy effect on the immune system, while high-intensity exercise has the opposite effect. Importantly, exercise is also intimately related to mitochondria. Thus, exercise is likely to regulate innate immunity through the release of mitochondria DAMPs. This paper reviews the link between mitochondrial DAMPs and innate immunity and explores the role of exercise in it, so as to provide new research ideas for the regulation mechanism of exercise on innate immunity from the perspective of mitochondria.

Abstract:Transactive response DNA binding protein 43 (TDP-43), an alternative-splicing regulator, can specifically bind the TG-rich DNAs, which is associated with a range of neurodegenerative diseases. Molecular dynamics simulation, although powerful in exploring inter-molecular interactions, is time-consuming, and moreover it is difficult to sample sufficiently the conformations for the system with large conformational changes to study the allosteric behavior. Here, we utilize a coarse-grained, elastic potential-based Gaussian network model (GNM) to characterize the interacting dynamics between human TDP-43 and DNA. Furtherly, using our group’s previously proposed thermodynamic cycle method based on GNM, we identify the key residues for DNA binding whose perturbations induce a large change in their binding free energy. The results reveal that upon DNA binding, an evident loss of flexibility occurs to TDP-43’s loop1 and loop3 segments rich in positively charged resides, which indicates their induced fit role in TDP-43-DNA recognition and interactions. Additionally, the thermodynamic cycle method identifies not only the residues important for DNA specific binding, but also the ones far away from the binding interface but critical for the conformational changes of TDP-43 caused by the DNA binding. This study is helpful for the understanding of the specific interaction between TDP-43 and DNA, and can provide important information for the related drug design. In addition, this method can be easily extended to other protein-nucleic acid interacting dynamics studies.

Abstract:Full-field label-free optical angiography is a powerful imaging technique that aids study of cardiovascular diseases in live animal models. Here, we presented a novel method that combined absorption intensity fluctuation modulation imaging with sub-pixel matching based on a normalized cross-correlation algorithm to eliminate blurring of angiograms caused by system drift or biological jitter. Raw images showing absorption difference between red blood cells and background tissue under illumination with low-coherence light were captured and divided into several short image sequences. These sequences were then used for image reconstruction using absorption intensity fluctuation modulation imaging to achieve full-field angiography by isolating dynamic red blood cell signals from the background signal in the frequency domain. All the reconstructed images were then matched with the first reconstructed image using the normalized cross-correlation algorithm and subsequently fused. In vivo angiography near chicken embryo heart was performed to demonstrate the efficacy of our method, and it produced clear, blur-free angiograms with high spatial resolution and signal-to-noise ratio.