A spatiotemporal atlas of mouse liver homeostasis and regeneration.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/ß-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

The 3-Dimensional Intelligent Structured Light Technique: A New Registration Method in Stereotactic Neurosurgery.

BACKGROUND AND OBJECTIVES: Surface-based facial scanning registration emerged as an essential registration method in the robot-assisted neuronavigation surgery, providing a marker-free way to align a patient's facial surface with the imaging data. The 3-dimensional (3D) structured light was developed as an advanced registration method based on surface-based facial scanning registration. We aspire to introduce the 3D structured light as a new registration method in the procedure of the robot-assisted neurosurgery and assess the accuracy, efficiency, and safety of this method by analyzing the relative operative results. METHODS: We analyzed the results of 47 patients who underwent Ommaya reservoir implantation (n = 17) and stereotactic biopsy (n = 30) assisted by 3D structured light at our hospital from January 2022 to May 2023. The accuracy and additional operative results were analyzed. RESULTS: For the Ommaya reservoir implantation, the target point error was 3.2 ± 2.2 mm and the entry point error was 3.3 ± 2.4 mm, while the operation duration was 35.8 ± 8.3 minutes. For the stereotactic biopsy, the target point error was 2.3 ± 1.3 mm and the entry point error was 2.7 ± 1.2 mm, while the operation duration was 24.5 ± 6.3 minutes. CONCLUSION: The 3D structured light technique reduces the patients' discomfort and offers the advantage of a simpler procedure, which can improve the clinical efficiency with the sufficient accuracy and safety to meet the clinical requirements of the puncture and navigation.

Neurotrophin-3 from the dentate gyrus supports postsynaptic sites of mossy fiber-CA3 synapses and hippocampus-dependent cognitive functions.

At the center of the hippocampal tri-synaptic loop are synapses formed between mossy fiber (MF) terminals from granule cells in the dentate gyrus (DG) and proximal dendrites of CA3 pyramidal neurons. However, the molecular mechanism regulating the development and function of these synapses is poorly understood. In this study, we showed that neurotrophin-3 (NT3) was expressed in nearly all mature granule cells but not CA3 cells. We selectively deleted the NT3-encoding Ntf3 gene in the DG during the first two postnatal weeks to generate a Ntf3 conditional knockout (Ntf3-cKO). Ntf3-cKO mice of both sexes had normal hippocampal cytoarchitecture but displayed impairments in contextual memory, spatial reference memory, and nest building. Furthermore, male Ntf3-cKO mice exhibited anxiety-like behaviors, whereas female Ntf3-cKO showed some mild depressive symptoms. As MF-CA3 synapses are essential for encoding of contextual memory, we examined synaptic transmission at these synapses using ex vivo electrophysiological recordings. We found that Ntf3-cKO mice had impaired basal synaptic transmission due to deficits in excitatory postsynaptic currents mediated by AMPA receptors but normal presynaptic function and intrinsic excitability of CA3 pyramidal neurons. Consistent with this selective postsynaptic deficit, Ntf3-cKO mice had fewer and smaller thorny excrescences on proximal apical dendrites of CA3 neurons and lower GluR1 levels in the stratum lucidum area where MF-CA3 synapses reside but normal MF terminals, compared with control mice. Thus, our study indicates that NT3 expressed in the dentate gyrus is crucial for the postsynaptic structure and function of MF-CA3 synapses and hippocampal-dependent memory.

Genetic Dissection of BDNF and TrkB Expression in Glial Cells.

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL) as well as a lower level of truncated TrkB (TrkB.T). However, there are conflicting reports regarding the expression of BDNF and TrkB in glial cells, particularly microglia. In this study, we employed a sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent reporter mice to label BDNF- or TrkB-expressing cells with soma-localized EGFP. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB-expressing microglia in examined CNS regions, including the somatomotor cortex, hippocampal CA1, and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the hippocampus of adult brains. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF in the hippocampus, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the hippocampus of adult mice. These results not only clarify the expression of BDNF and TrkB in glial cells but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in astrocytes and oligodendrocytes.

Fast Interfacial Carrier Dynamics Modulated by Bidirectional Charge Transport Channels in ZnIn2 S4 -based Composite Photoanodes Probed by Scanning Photoelectrochemical Microscopy.

Limited charge separation/transport efficiency remains the primary obstacle of achieving satisfying photoelectrochemical (PEC) water splitting performance. Therefore, it is essential to develop diverse interfacial engineering strategies to mitigate charge recombination. Despite obvious progress having been made, most works only considered a single-side modulation in either the electrons of conduction band or the holes of valence band in a semiconductor photoanode, leading to a limited PEC performance enhancement. Beyond this conventional thinking, we developed a novel coupling modification strategy to achieve a composite electrode with bidirectional carrier transport for a better charge separation, in which Ti2 C3 Tx MXene quantum dots (MQDs) and α-Fe2 O3 nanodots (FO) are anchored on the surface of ZnIn2 S4 (ZIS) nanoplates, resulting in markedly improved PEC water splitting of pure ZIS photoanode. Systematic studies indicated that the bidirectional charge transfer pathways were stimulated due to MQDs as "electron extractor" and S-O bonds as carriers transport channels, which synergistically favors significantly enhanced charge separation. The enhanced kinetic behavior at the FO/MQDs/ZIS interfaces was systematically and quantitatively evaluated by a series of methods, especially scanning photoelectrochemical microscopy. This work may deepen our understanding of interfacial charge separation, and provide valuable guidance for the rational design and fabrication of high-performance composite electrodes.

Difunctional Ag nanoparticles with high lithiophilic and conductive decorate on core-shell SiO2 nanospheres for dendrite-free lithium metal anodes.

Lithium metal is an attractive and promising anode material due to its high energy density and low working potential. However, the uncontrolled growth of lithium dendrites during repeated plating and stripping processes hinders the practical application of lithium metal batteries, leading to low Coulombic efficiency, poor lifespan, and safety concerns. In this study, we synthesized highly lithiophilic and conductive Ag nanoparticles decorated on SiO2 nanospheres to construct an optimized lithium host for promoting uniform Li deposition. The Ag nanoparticles not only act as lithiophilic sites but also provide high electrical conductivity to the Ag@SiO2@Ag anode. Additionally, the SiO2 layer serves as a lithiophilic nucleation agent, ensuring homogeneous lithium deposition and suppressing the growth of lithium dendrites. Theoretical calculations further confirm that the combination of Ag nanoparticles and SiO2 effectively enhances the adsorption ability of Ag@SiO2@Ag with Li+ ions compared to pure Ag and SiO2 materials. As a result, the Ag@SiO2@Ag coating, with its balanced lithiophilicity and conductivity, demonstrates excellent electrochemical performance, including high Coulombic efficiency, low polarization voltage, and long cycle life. In a full lithium metal cell with LiFePO4 cathode, the Ag@SiO2@Ag anode exhibits a high capacity of 133.1 and 121.4 mAh/g after 200 cycles at rates of 0.5 and 1C, respectively. These results highlight the synergistic coupling of lithiophilicity and conductivity in the Ag@SiO2@Ag coating, providing valuable insights into the field of lithiophilic chemistry and its potential for achieving high-performance batteries in the next generation.

Analysis and Prediction of Significant Genes in Gastric Cancer Based on TCGA Database.

OBJECTIVE: Use TCGA data to screen the significantly expressed genes in gastric cancer,then analyze the biological functions of characteristic genes.To identify potential targets for the diagnosis, prognosis and therapeutic monitoring of gastric cancer. METHODS: Download the high-throughput gastric cancer patient tissue mRNA expression data from the TCGA database, and used the edgeR software package to perform gene differences using the Rstudio software according to the |logFC|>1 and p<0.05 standards analysis, then performed enrichment analysis and constructed protein interaction network of the differently expressed genes to find the significant genes.Finally,analyzed the relationship between significant genes and gastric cancer patient prognosis. RESULTS: The RNA-seq expression data of 375 cases of gastric cancer and 32 adjacent tissues were obtained from the TCGA database. The differential analysis yielded 4320 differential genes, of which 2718 were highly expressed and 1602 were low expressed. Through enrichment analysis, it is found that the differential genes are mainly related to the neural active ligand-receptor interaction, calcium signaling pathway, Protein digestion and absorption, chemical carcinogenesis, and cytochrome P450 metabolism of foreign compounds. Further survival analysis screened out the five significant genes of ALB, AFP, IGFBP1, APOH, and TF are related to the prognosis of gastric cancer. CONCLUSION: The five significant genes screened by TCGA data may be related to the prognosis of gastric cancer and are expected to become prognostic biomarkers.

Adaptive laboratory evolution of Rhodococcus rhodochrous DSM6263 for chlorophenol degradation under hypersaline condition.

BACKGROUND: Normally, a salt amount greater than 3.5% (w/v) is defined as hypersaline. Large amounts of hypersaline wastewater containing organic pollutants need to be treated before it can be discharged into the environment. The most critical aspect of the biological treatment of saline wastewater is the inhibitory/toxic effect exerted on bacterial metabolism by high salt concentrations. Although efforts have been dedicated to improving the performance through the use of salt-tolerant or halophilic bacteria, the diversities of the strains and the range of substrate spectrum remain limited, especially in chlorophenol wastewater treatment. RESULTS: In this study, a salt-tolerant chlorophenol-degrading strain was generated from Rhodococcus rhodochrous DSM6263, an original aniline degrader, by adaptive laboratory evolution. The evolved strain R. rhodochrous CP-8 could tolerant 8% NaCl with 4-chlorophenol degradation capacity. The synonymous mutation in phosphodiesterase of strain CP-8 may retard the hydrolysis of cyclic adenosine monophosphate (cAMP), which is a key factor reported in the osmoregulation. The experimentally verified up-regulation of intracellular cAMP level in the evolved strain CP-8 contributes to the improvement of growth phenotype under high osmotic condition. Additionally, a point mutant of the catechol 1,2-dioxygenase, CatAN211S, was revealed to show the 1.9-fold increment on activity, which the mechanism was well explained by molecular docking analysis. CONCLUSIONS: This study developed one chlorophenol-degrading strain with extraordinary capacity of salt tolerance, which showed great application potential in hypersaline chlorophenol wastewater treatment. The synonymous mutation in phosphodiesterase resulted in the change of intracellular cAMP concentration and then increase the osmotic tolerance in the evolved strain. The catechol 1,2-dioxygenase mutant with improved activity also facilitated chlorophenol removal since it is the key enzyme in the degradation pathway.

The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment. METHODS: We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model. RESULTS: We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC. CONCLUSIONS: Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.

BACKGROUND: The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. METHODS: The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. RESULTS: A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations. CONCLUSIONS: Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.

Genetic dissection of BDNF and TrkB expression in glial cells.

The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL), and a lower level of truncated TrkB (TrkB.T). With conflicting results, glial cells also have been reported to express BDNF and TrkB. In the current study, we employed a more sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain. We utilized three Cre mouse strains in which Cre recombinase is expressed in the same cells as BDNF, TrkB.FL, or all TrkB isoforms, and crossed them to Cre-dependent EGFP reporter mice to label BDNF- or TrkB- expressing cells. We performed immunohistochemistry with glial cell markers to examine the expression of BDNF and TrkB in microglia, astrocytes, and oligodendrocytes. Surprisingly, we found no BDNF- or TrkB- expressing microglia in the brain and spinal cord. Consistent with previous studies, most astrocytes only express TrkB.T in the adult brain. Moreover, there are a small number of astrocytes and oligodendrocytes that express BDNF, the function of which is to be determined. We also found that oligodendrocyte precursor cells, but not mature oligodendrocytes, express both TrkB.FL and TrkB.T in the adult brain. These results not only clarify the expression of BDNF and TrkB in glial cells, but also open opportunities to investigate previously unidentified roles of BDNF and TrkB in glial cells.

Response of nutrient loss to natural erosive rainfall events under typical tillage practices of contour ridge system in the rocky mountain areas of Northern China.

Changes in natural rainfall characterized by heavy precipitation and high rainfall intensity would increase the risks and uncertainty of nutrients losses. Losses of nitrogen (N) and phosphorus (P) with water erosion from agriculture-related activities has become the principal nutrients resulting the eutrophication of water bodies. However, a little attention has been paid to the loss characteristic of N and P responding to natural rainfall in widely used contour ridge systems. To explore the loss mechanism of N and P in contour ridge system, nutrient loss associated with runoff and sediment yield was observed in in situ runoff plots of sweet potato (SP) and peanut (PT) contour ridges under natural rainfall. Rainfall events were divided into light rain, moderate rain, heavy rain, rainstorm, large rainstorm, and extreme rainstorm level, and rainfall characteristics for each rainfall level were recorded. Results showed that rainstorm, accounting for 46.27% of the total precipitation, played a destructive role in inducing runoff, sediment yield, and nutrient loss. The average contribution of rainstorm to sediment yield (52.30%) was higher than that to runoff production (38.06%). Rainstorm respectively generated 43.65-44.05% of N loss and 40.71-52.42% of P loss, although light rain induced the greatest enrichment value for total nitrogen (TN, 2.44-4.08) and PO4-P (5.40). N and P losses were dominated by sediment, and up to 95.70% of the total phosphorus and 66.08% of TN occurred in sediment. Nutrient loss exhibited the highest sensitivity to sediment yield compared to runoff and rainfall variables, and a significant positive linear relationship was observed between nutrient loss and sediment yield. SP contour ridge presented higher nutrient loss than that in PT contour ridge, especially for P loss. Findings gained in this study provide references for the response strategies of nutrient loss control to natural rainfall change in contour ridge system.

Potential ecological risks of heavy metals and Cd accumulation characteristics of Suaeda salsa under different Cd input and water logging conditions in the Yellow River estuary, China.

To improve the remediation of heavy metal pollution by typical wetland vegetation and maintain the health of wetland ecosystems under the water-sediment regulation scheme (WSRS) application, we evaluated the potential ecological risk of heavy metals in surface sediment in the Yellow River estuary affected by the WSRS. The ranges of Cr, Cu, Zn, Cd, and Pb content in surface sediment were 52.44-100.80 mg·kg-1 dry weight (DW), 16.38-21.19 mg·kg-1 DW, 64.77-255.50 mg·kg-1 DW, 0.12-0.24 mg·kg-1 DW, and 5.40-8.63 mg·kg-1 DW, respectively, and potential ecological risk coefficients showed that Cd was associated with moderate potential risk. We further examined effects of Cd in a greenhouse experiment to explore the influence of short-term Cd input and water logging condition changes induced by WSRS on the Cd absorption characteristics of Suaeda salsa (L.) Pall in the Yellow River estuary. The results showed that total biomass decreased but Cd content in tissue of S. salsa increased with increasing Cd input and the accumulation factor reached maximum values at 100 µg·L-1 of Cd, indicating that S. salsa efficiently accumulated Cd. Water logging depth significantly affected S. salsa growth and Cd absorption with deeper water logging being detrimental to growth. The interaction effect of Cd input and water logging depth on Cd content and accumulation factor was significant. These results suggest that WSRS caused short-term heavy metal input and changes in water conditions affect wetland vegetation growth and heavy metal absorption in the downstream estuary.

Cell atlas of CCl 4-induced progressive liver fibrosis reveals stage-specific responses.

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl 4)-induced progressive liver fibrosis. Integrative analysis distinguished the sequential responses to injury of hepatocytes, hepatic stellate cells and endothelial cells. Moreover, we reconstructed cell-cell interactions and gene regulatory networks implicated in these processes. These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions, dysfunction for clearance by apoptosis of activated hepatic stellate cells, accumulation of pro-fibrotic signals, and the switch from an anti-angiogenic to a pro-angiogenic program during CCl 4-induced progressive liver fibrosis. Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

Gradient Graphdiyne Induced Copper and Oxygen Vacancies in Cu0.95 V2 O5 Anodes for Fast-Charging Lithium-Ion Batteries.

Vacancies can significantly affect the performance of metal oxide materials. Here, a gradient graphdiyne (GDY) induced Cu/O-dual-vacancies abundant Cu0.95 V2 O5 @GDY heterostructure material has been prepared as a competitive fast-charging anode material. Cu0.95 V2 O5 self-catalyzes the growth of gradient GDY with rich alkyne-alkene complex in the inner layer and rich alkyne bonds in the outer layer, leading to the formation of Cu and O vacancies in Cu0.95 V2 O5 . The synergistic effect of vacancies and gradient GDY results in the electron redistribution at the hetero-interface to drive the generation of a built-in electric field. Thus, the Li-ion transport kinetics, electrochemical reaction reversibility and Li storage sites of Cu0.95 V2 O5 are greatly enhanced. The Cu0.95 V2 O5 @GDY anodes show excellent fast-charging performance with high capacities and negligible capacity decay for 10 000 cycles and 20 000 cycles at extremely high current densities of 5 A g-1 and 10 A g-1 , respectively. Over 30 % of capacity can be delivered in 35 seconds.

Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration.

Tissue regeneration requires coordination between resident stem cells and local niche cells1,2. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity3 was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol. We identified and isolated different senescent cell types from damaged muscles of young and old mice. Deeper transcriptome, chromatin and pathway analyses revealed conservation of cell identity traits as well as two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and ageing. Senescent cells create an aged-like inflamed niche that mirrors inflammation associated with ageing (inflammageing4) and arrests stem cell proliferation and regeneration. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. By contrast, transplantation of senescent cells delays regeneration. Our results provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle, and uncover unproductive functional interactions between senescent cells and stem cells in regenerative niches that can be overcome. As senescent cells also accumulate in human muscles, our findings open potential paths for improving muscle repair throughout life.

Synthesis of Crystalline Phosphine-Graphdiyne with Self-Adaptive p-π Conjugation.

"Dynamic" behavior materials with high surface activity and the ability of chemical bond conversion are the frontier materials in the field of renewable energy. The outstanding feature of these materials is that they have adaptive electronic properties that external stimuli can adjust. An original discovery in a new crystalline two-dimensional phosphine-graphdiyne (P-GDY) material is described here. Although the p-π conjugation of most trivalent phosphorus π-systems is insignificant because of the pyramidal configuration, the lone pair electrons of phosphorus atoms participate strongly in the delocalization under the influence of the interlayer van der Waals forces in P-GDY. Due to the dynamically reversible nature of noncovalent interactions (p-π conjugation), P-GDY exhibits a specific adaptive behavior and realizes the responsive reversible transport of a lithium ion by regulating p-π interactions. Our findings would provide the potential to develop a new family of responsive materials with tunable structures.

SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer.

The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.