LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis

Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine‐rich‐alpha‐2‐glycoprotein 1 (LRG‐1), that could promote fat graft survival through RAB31‐mediated inhibition of hypoxia‐induced apoptosis. We showed that LRG‐1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG‐1‐treated groups. Furthermore, we discovered that LRG‐1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG‐1‐mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG‐1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat.     

Scalable manufacturing of clinical‐grade differentiated cardiomyocytes derived from human‐induced pluripotent stem cells for regenerative therapy

Basic research on human pluripotent stem cell (hPSC)‐derived cardiomyocytes (CMs) for cardiac regenerative therapy is one of the most active and complex fields to achieve this alternative to heart transplantation and requires the integration of medicine, science, and engineering. Mortality in patients with heart failure remains high worldwide. Although heart transplantation is the sole strategy for treating severe heart failure, the number of donors is limited. Therefore, hPSC‐derived CM (hPSC‐CM) transplantation is expected to replace heart transplantation. To achieve this goal, for basic research, various issues should be considered, including how to induce hPSC proliferation efficiently for cardiac differentiation, induce hPSC‐CMs, eliminate residual undifferentiated hPSCs and non‐CMs, and assess for the presence of residual undifferentiated hPSCs in vitro and in vivo. In this review, we discuss the current stage of resolving these issues and future directions for realizing hPSC‐based cardiac regenerative therapy.

Heart disease is the leading cause of death worldwide. No cure for severe heart failure has been established other than heart transplantation, and the number of donors is insufficient. Therefore, hPSC‐derived CM (hPSC‐CM) transplantation is expected to replace heart transplantation. To prepare a large number of hPSC‐CMs more efficiently, an effective method for proliferating hPSCs while maintaining their undifferentiated state is needed. It is also desirable to induce large numbers of hPSC‐CMs at the same time and develop non‐invasive methods to prepare hPSC‐CMs only. Then. it is crucial to completely eliminate the undifferentiated hPSCs in advance to ensure a safe hiPSC‐CM transplantation for regenerative therapy. Moreover, assessment of the presence of residual undifferentiated hPSCs in vitro and in vivo should be considered. After evaluating the contamination of hPSCs in vitro, cardiac spheroids are generated for transplantation, and these spheroids are measured for contractility.     

Long‐term nitrogen enrichment mediates the effects of nitrogen supply and co‐inoculation on a viral pathogen

Host nutrient supply can mediate host–pathogen and pathogen–pathogen interactions. In terrestrial systems, plant nutrient supply is mediated by soil microbes, suggesting a potential role of soil microbes in plant diseases beyond soil‐borne pathogens and induced plant defenses. Long‐term nitrogen (N) enrichment can shift pathogenic and nonpathogenic soil microbial community composition and function, but it is unclear if these shifts affect plant–pathogen and pathogen–pathogen interactions. In a growth chamber experiment, we tested the effect of long‐term N enrichment on infection by Barley Yellow Dwarf Virus (BYDV‐PAV) and Cereal Yellow Dwarf Virus (CYDV‐RPV), aphid‐vectored RNA viruses, in a grass host. We inoculated sterilized growing medium with soil collected from a long‐term N enrichment experiment (ambient, low, and high N soil treatments) to isolate effects mediated by the soil microbial community. We crossed soil treatments with a N supply treatment (low, high) and virus inoculation treatment (mock‐, singly‐, and co‐inoculated) to evaluate the effects of long‐term N enrichment on plant–pathogen and pathogen–pathogen interactions, as mediated by N availability. We measured the proportion of plants infected (i.e., incidence), plant biomass, and leaf chlorophyll content. BYDV‐PAV incidence (0.96) declined with low N soil (to 0.46), high N supply (to 0.61), and co‐inoculation (to 0.32). Low N soil mediated the effect of N supply on BYDV‐PAV: instead of N supply reducing BYDV‐PAV incidence, the incidence increased. Additionally, ambient and low N soil ameliorated the negative effect of co‐inoculation on BYDV‐PAV incidence. BYDV‐PAV infection only reduced chlorophyll when plants were grown with low N supply and ambient N soil. There were no significant effects of long‐term N soil on CYDV‐RPV incidence. Soil inoculant with different levels of long‐term N enrichment had different effects on host–pathogen and pathogen–pathogen interactions, suggesting that shifts in soil microbial communities with long‐term N enrichment may mediate disease dynamics.     

T‐cell infiltration,contribution and regulation in the central nervous system post‐traumatic injury

T cells participate in the repair process and immune response in the CNS post‐traumatic injury and play both a beneficial and harmful role. Together with nerve cells and other immune cells, they form a microenvironment in the CNS post‐traumatic injury. The repair of traumatic CNS injury is a long‐term process. T cells contribute to the repair of the injury site to influence the recovery. Recently, with the advance of new techniques, such as mass spectrometry‐based flow cytometry, modern live‐cell imaging, etc, research focusing on T cells is becoming one of the valuable directions for the future therapy of traumatic CNS injury. In this review, we summarized the infiltration, contribution and regulation of T cells in post‐traumatic injury, discussed the clinical significance and predicted the future research direction.     

Space‐for‐time is not necessarily a substitution when monitoring the distribution of pelagic fishes in the San Francisco Bay‐Delta

Occupancy models are often used to analyze long‐term monitoring data to better understand how and why species redistribute across dynamic landscapes while accounting for incomplete capture. However, this approach requires replicate detection/non‐detection data at a sample unit and many long‐term monitoring programs lack temporal replicate surveys. In such cases, it has been suggested that surveying subunits within a larger sample unit may be an efficient substitution (i.e., space‐for‐time substitution). Still, the efficacy of fitting occupancy models using a space‐for‐time substitution has not been fully explored and is likely context dependent. Herein, we fit occupancy models to Delta Smelt (Hypomesus transpacificus) and Longfin Smelt (Spirinchus thaleichthys) catch data collected by two different monitoring programs that use the same sampling gear in the San Francisco Bay‐Delta, USA. We demonstrate how our inferences concerning the distribution of these species changes when using a space‐for‐time substitution. Specifically, we found the probability that a sample unit was occupied was much greater when using a space‐for‐time substitution, presumably due to the change in the spatial scale of our inferences. Furthermore, we observed that as the spatial scale of our inferences increased, our ability to detect environmental effects on system dynamics was obscured, which we suspect is related to the tradeoffs associated with spatial grain and extent. Overall, our findings highlight the importance of considering how the unique characteristics of monitoring programs influences inferences, which has broad implications for how to appropriately leverage existing long‐term monitoring data to understand the distribution of species.     

Advances in single‐cell sequencing and its application to musculoskeletal system research

In recent years, single‐cell sequencing (SCS) technologies have continued to advance with improved operating procedures and reduced cost, leading to increasing practical adoption among researchers. These emerging technologies have superior abilities to analyse cell heterogeneity at a single‐cell level, which have elevated multi‐omics research to a higher level. In some fields of research, application of SCS has enabled many valuable discoveries, and musculoskeletal system offers typical examples. This article reviews some major scientific issues and recent advances in musculoskeletal system. In addition, combined with SCS technologies, the research of cell or tissue heterogeneity in limb development and various musculoskeletal system clinical diseases also provides new possibilities for treatment strategies. Finally, this article discusses the challenges and future development potential of SCS and recommends the direction of future applications of SCS to musculoskeletal medicine.     

Single‐cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin‐driven circadian network

Circadian rhythms in mammals are governed by the hypothalamic suprachiasmatic nucleus (SCN), in which 20,000 clock cells are connected together into a powerful time‐keeping network. In the absence of network‐level cellular interactions, the SCN fails as a clock. The topology and specific roles of its distinct cell populations (nodes) that direct network functions are, however, not understood. To characterise its component cells and network structure, we conducted single‐cell sequencing of SCN organotypic slices and identified eleven distinct neuronal sub‐populations across circadian day and night. We defined neuropeptidergic signalling axes between these nodes, and built neuropeptide‐specific network topologies. This revealed their temporal plasticity, being up‐regulated in circadian day. Through intersectional genetics and real‐time imaging, we interrogated the contribution of the Prok2‐ProkR2 neuropeptidergic axis to network‐wide time‐keeping. We showed that Prok2‐ProkR2 signalling acts as a key regulator of SCN period and rhythmicity and contributes to defining the network‐level properties that underpin robust circadian co‐ordination. These results highlight the diverse and distinct contributions of neuropeptide‐modulated communication of temporal information across the SCN.     

Vegetation resistance and resilience to a decade‐long dry period in the temperate grasslands in China

The duration of climate anomalies has been increasing across the globe, leading to ecosystem function loss. Thus, we need to understand the responses of the ecosystem to long‐term climate anomalies. It remains unclear how ecosystem resistance and resilience respond to long‐term climate anomalies, for example, continuous dry years at a regional scale. Taking the opportunity of a 13‐year dry period in the temperate grasslands in northern China, we quantified the resistance and resilience of the grassland in response to this periodic dry period. We found vegetation resistance to the dry period increased with mean annual precipitation (MAP), while resilience increased at first until at MAP of 250 mm and then decreased slightly. No trade‐off between resistance and resilience was detected when MAP < 250 mm. Our results highlight that xeric ecosystems are most vulnerable to the long‐term dry period. Given expected increases in drought severity and duration in the coming decades, our findings may be helpful to identify vulnerable ecosystems in the world for the purpose of adaptation.