Crystal-Phase-Engineered High-Entropy Alloy Aerogels for Enhanced Ethylamine Electrosynthesis from Acetonitrile.

Crystal-phase engineering that promotes the rearrangement of active atoms to form new structural frameworks achieves excellent result in the field of electrocatalysis and optimizes the performance of various electrochemical reactions. Herein, for the first time, it is found that the different components in metallic aerogels will affect the crystal-phase transformation, especially in high-entropy alloy aerogels (HEAAs), whose crystal-phase transformation during annealing is more difficult than medium-entropy alloy aerogels (MEAAs), but they still show better electrochemical performance. Specifically, PdPtCuCoNi HEAAs with the parent phase of face-centered cubic (FCC) PdCu possess excellent 89.24% of selectivity, 746.82 mmol h-1 g-1 cat. of yield rate, and 90.75% of Faraday efficiency for ethylamine during acetonitrile reduction reaction (ARR); while, maintaining stability under 50 h of long-term testing and ten consecutive electrolysis cycles. The structure-activity relationship indicates that crystal-phase regulation from amorphous state to FCC phase promotes the atomic rearrangement in HEAAs, thereby optimizing the electronic structure and enhancing the adsorption strength of reaction intermediates, improving the catalytic performance. This study provides a new paradigm for developing novel ARR electrocatalysts and also expands the potential of crystal-phase engineering in other application areas.

Hypermethylation of Bmp2 and Fgfr2 Promoter Regions in Bone Marrow Mesenchymal Stem Cells Leads to Bone Loss in Prematurely Aged Mice.

Osteoporosis is an age-related, systemic skeletal disease that poses a significant public health challenge in contemporary society. Development at the epigenetic level is emerging as an important pathogenic mechanism of osteoporosis. Despite indications of a robust association between DNA methylation and osteoporosis development, a comprehensive understanding of the specific role of DNA methylation in osteoporosis remains limited. In this study, significant bone loss was detected at the beginning of eight weeks of age in mouse models of premature aging (SHJHhr mice). We identified a notable upregulation of DNA methyltransferase 3b/3l (Dnmt3b/l) and downregulation of ten eleven translocation dioxygenase 1 (Tet1) in bone marrow mesenchymal stem cells (BMSCs) isolated from SHJHhr mice, along with an increase in the overall 5-methylcytosine (5mC) levels. Moreover, methylation capture sequencing revealed genomic hypermethylation in SHJHhr mice BMSCs. Integrated methylome and transcriptome analyses revealed several crucial methylated genes and networks that are potentially associated with osteoporosis development. Notably, elevated methylation levels of genes linked to the Wnt signaling pathway, particularly bone morphogenetic protein 2 (Bmp2) and fibroblast growth factor receptor (Fgfr2), appeared to compromise the osteogenic differentiation potential of BMSCs. Concurrently, DNA methyltransferase inhibitors attenuated the methylation of the promoter regions of Bmp2 and Fgfr2 and rescued the osteogenic differentiation potential of the BMSCs from SHJHhr mice. In summary, our study provides novel insights into the role of DNA methylation in the development of osteoporosis and suggests promising prospects for employing epigenetic interventions to manage osteoporosis.

Amorphous ZnSnOx Hollow Spheres Enable Highly Efficient CO2 Reduction.

Carbon dioxide (CO2) adsorption and electron transport play an important role in CO2 reduction reaction (CO2RR). Herein, we have demonstrated a new class of diverse hollow ZnSnOx (ZSO) through the amorphization of hydroxides to enhance CO2 adsorption and accelerate electron transport. The amorphization is occurred by calcination process, as indicated by Fourier transform infrared spectroscopy and Raman spectra. In particular, the ZnSnOx hollow spheres (ZSO HSs) achieve a high Faradaic efficiency (FE) of HCOOH up to 92.7 % at best, outperforming the commercial ZSO (Comm. ZSO, 85.7 %). ZSO HSs also exhibit durable stability with negligible activity decay after 10 h of successive electrolysis. In-situ attenuated total reflectance infrared absorption spectroscopy further reveals strong adsorption of CO2 and rapid intermediate configuration transformation in amorphous ZSO HSs. This work demonstrates the practical application of ZSO for CO2RR and provides a new insight to create efficient CO2RR electrocatalysts.

Freeze-Thaw Damage Characteristics of Concrete Based on Compressive Mechanical Properties and Acoustic Parameters.

Concrete is a versatile material widely used in modern construction. However, concrete is also subject to freeze-thaw damage, which can significantly reduce its mechanical properties and lead to premature failure. Therefore, the objective of this study was to assess the laboratory performance and freeze-thaw damage characteristics of a common mix proportion of concrete based on compressive mechanical tests and acoustic technologies. Freeze-thaw damage characteristics of the concrete were evaluated via compressive mechanical testing, mass loss analysis, and ultrasonic pulse velocity testing. Acoustic emission (AE) technology was utilized to assess the damage development status of the concrete. The outcomes indicated that the relationships between cumulative mass loss, compressive strength, and ultrasonic wave velocity and freeze-thaw cycles during the freezing-thawing process follow a parabola fitting pattern. As the freeze-thaw damage degree increased, the surface presented a trend of "smooth intact surface" to "surface with dense pores" to "cement mortar peeling" to "coarse aggregates exposed on a large area". Therefore, there was a rapid decrease in the mass loss after a certain number of freeze-thaw cycles. According to the three stages divided by the stress-AE parameter curve, the linear growth stage shortens, the damage accumulation stage increases, and the failure stage appears earlier with the increase in freeze-thaw cycles. In conclusion, the application of a comprehensive understanding of freeze-thaw damage characteristics of concrete based on compressive properties and acoustic parameters would enhance the evaluation of the performance degradation and damage status for concrete structures.

A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-Tumor Immune Response via Eliciting Type I Interferon Signaling.

Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.

Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8+T cells.

Tumors employ diverse strategies for immune evasion. Unraveling the mechanisms by which tumors suppress anti-tumor immunity facilitates the development of immunotherapies. Here, we have identified tumor-secreted fibroblast growth factor 21 (FGF21) as a pivotal immune suppressor. FGF21 is upregulated in multiple types of tumors and promotes tumor progression. Tumor-secreted FGF21 significantly disrupts anti-tumor immunity by rewiring cholesterol metabolism of CD8+T cells. Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. FGF21 knockdown or blockade using a neutralizing antibody normalizes AKT-mTORC1 signaling and reduces excessive cholesterol accumulation in CD8+T cells, thus restoring CD8+T cytotoxic function and robustly suppressing tumor growth. Our findings reveal FGF21 as a "secreted immune checkpoint" that hampers anti-tumor immunity, suggesting that inhibiting FGF21 could be a valuable strategy to enhance the cancer immunotherapy efficacy.

Lattice-Strained Metallic Aerogels as Efficient and Anti-Poisoning Electrocatalysts for Oxygen Reduction Reaction.

Lattice strain engineering optimizes the interaction between the catalytic surface and adsorbed molecules. This is done by adjusting the electron and geometric structure of the metal site to achieve high electrochemical performance, but, to date, it has been rarely reported on anti-poisoned oxygen reduction reaction (ORR). Herein, lattice-strained Pd@PdBiCo quasi core-shell metallic aerogels (MAs) were designed by "one-pot and two-step" method for anti-poisoned ORR. Pd@PdBiCo MAs/C maintain their original activity (1.034 A mgPd -1 ) in electrolytes with CH3 OH and CO at 0.85 V vs. reversible hydrogen electrode (RHE), outperforming the commercial Pd/C (0.156 A mgPd -1 ), Pd MAs/C (0.351 A mgPd -1 ), and PdBiCo MAs/C (0.227 A mgPd -1 ). Moreover, Pd@PdBiCo MAs/C also show high stability and anti-poisoning with negligible activity decay after 8000 cycles in 0.1 m KOH+0.3 m CH3 OH. These results of X-ray photoelectron spectroscopy, CO stripping, and diffuses reflectance FTIR spectroscopy reveal that the tensile strain and strong interaction between different elements of Pd@PdBiCo MAs/C effectively optimize the electronic structure to promote O2 adsorption and activation, while suppressing CH3 OH oxidation and CO adsorption, leading to high ORR activity and anti-poisoning property. This work inspires the rational design of MAs in fuel cells and beyond.

Sensitivity and Reliability Analysis of Ultrasonic Pulse Parameters in Evaluating the Laboratory Properties of Asphalt Mixtures.

The ultrasonic test is a promising non-destructive testing technique for evaluating the properties of asphalt mixtures. To investigate the applicability and reliability of ultrasonic testing technology (UTT) in evaluating the performance of asphalt mixtures, ultrasonic tests, indirect tensile tests, compression tests, and dynamic modulus tests were carried out at various temperatures. Subsequently, the distribution characteristics of ultrasonic traveling parameters for asphalt mixtures were analyzed. The variation of ultrasonic pulse velocity and amplitude in dry and wet states with temperature was studied. Then, the correlation between the ultrasonic parameters and both the volume parameters and the mechanical performance parameters of asphalt mixtures was revealed, and the functional relationship between ultrasonic pulse velocity and compressive strength was established. Finally, the reliability of predicting high-frequency dynamic modulus by ultrasonic velocity was verified. The laboratory tests and analysis results indicate that both ultrasonic pulse velocity and amplitude in dry and wet conditions show a decreasing trend with an increase in temperature. Ultrasonic parameters are greatly influenced by asphalt content and mineral aggregate content of 9.5~13.2 mm and 13.2~16 mm. The dynamic modulus at a high-frequency load can be predicted by using ultrasonic velocity, and predicting the results for OGFC and SMA mixtures deduced by using the UPV at a high-frequency load have higher reliability.

Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy affecting women, characterized by a substantial occurrence rate. Squalene epoxidase (SQLE) is a crucial regulator of ferroptosis and has been associated with promoting cell growth and invasion in different types of human cancers. This study aimed to investigate the functional significance of SQLE in BC and elucidate the underlying molecular mechanisms involved. METHODS: SQLE expression levels in BC tissues were evaluated using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Cell viability, invasion, migration, and cell cycle distribution were assessed using a combination of assays, including the Cell Counting Kit-8, EdU, colony formation, Transwell, and wound healing assays and flow cytometry analysis. Measurement of intracellular reactive oxygen species (ROS), malondialdehyde assay, and glutathione assay were utilized to investigate ferroptosis. Furthermore, co-immunoprecipitation and immunofluorescence assays were conducted to explore the correlation between SQLE and CCNB1. The in vivo tumor growth was evaluated by conducting a xenograft tumorigenicity assay to investigate the impact of SQLE. RESULTS: SQLE expression was significantly increased in BC, and higher SQLE expression levels were significantly associated with an unfavorable prognosis. In vitro functional assays revealed that the overexpression of SQLE markedly enhanced the proliferation, migration, and invasion capacities of BC cells. Furthermore, SQLE overexpression facilitated tumor growth in nude mice. Mechanistically, SQLE alleviated the ubiquitination modification of CCNB1, leading to enhanced stability of the CCNB1 protein and decreased intracellular ROS levels. Ultimately, this inhibited ferroptosis and facilitated the progression of BC. Our findings have provided insights into a crucial pathway by which elevated SQLE expression confers protection to BC cells against ferroptosis, thus promoting cancer progression. SQLE may serve as a novel oncological marker and a potential therapeutic target for BC progression. CONCLUSIONS: In conclusion, this study provides evidence that SQLE plays a regulatory role in BC progression by modulating CCNB1 and ferroptosis. These findings offer valuable insights into the role of SQLE in the pathogenesis of BC and demonstrate its potential as a therapeutic target for treating BC.

Alterations of oral microbiota are associated with the development and severity of acute pancreatitis.

Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as Streptococcus, Neisseria, and Gemella, and increased Prevotella, Veillonella, Granulicatella, Actinomyces, and Peptostreptococcus in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as Neisseria, Haemophilus, and Gemella in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that Prevotella, Peptostreptococcus, Actinomyces, and Porphyromonas were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.

Low-dose metronomic chemotherapy triggers oxidized mtDNA sensing inside tumor cells to potentiate CD8+T anti-tumor immunity.

Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is emerging as a promising form of chemotherapy utilization. LDM chemotherapy exerts immunomodulatory effects. However, the underlying mechanism is not fully understood. Here we found that suppressing tumor growth by LDM chemotherapy was dependent on the activation of CD8+T cells. LDM chemotherapy potentiated the cytotoxic function of CD8+T cells by stimulating cancer-cell autonomous type I interferon (IFN) induction. Mechanistically, LDM chemotherapy evoked mitochondrial dysfunction and increased reactive oxygen species (ROS) production. ROS triggered the oxidation of cytosolic mtDNA, which was sensed by cGAS-STING, consequently inducing type I IFN production in the cancer cells. Moreover, the cGAS-STING-IFN axis increased PD-L1 expression and predicted favorable clinical responses to chemoimmunotherapy. Antioxidant N-acetylcysteine inhibited oxidized mtDNA-induced type I IFN production and attenuated the efficacy of combination therapy with LDM chemotherapy and PD-L1 blockade. This study elucidates the critical role of intratumoral oxidized mtDNA sensing in LDM chemotherapy-mediated activation of CD8+T cell immune response. These findings may provide new insights for designing combinatorial immunotherapy for cancer patients.

Osteosarocma progression in biomimetic matrix with different stiffness: Insights from a three-dimensional printed gelatin methacrylamide hydrogel.

Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower drug sensitivity in a softer 3D matrix. When placed in a stiffer matrix, osteosarcoma cells secrete more MMP and VEGF, potentially to fight for survival and attract vascular invasion. Transcriptomic analysis showed that matrix stiffness could impact the signaling pathway of integrin α5-MAPK. The transplantation of 3D printed models in nude mice showed that cells encapsulated in the softer hydrogel were more likely to form subcutaneous tumors. These results suggest that matrix stiffness plays an important role in the development of osteosarcoma in a 3D environment and that inhibition of integrin α5 could block the signal transduction of matrix stiffness.

Evaluation and Correlation Analysis of the Rheological Properties of Ground Tire Rubber and Styrene Butadiene Styrene Compound-Modified Asphalt.

With the increase in highway traffic volume, many waste tires are being produced, which puts serious pressure on the global ecological environment. Processing waste tires into powder and adding them to asphalt is an important and effective way to solve this noticeable environmental challenge. In this paper, to produce ground tire rubber (GTR) and styrene-butadiene-styrene (SBS) compound-modified asphalt, GTR was put into SBS-modified asphalt (GTRSA). Subsequently, some ordinary property tests, frequency sweep tests, and multiple stress creep recovery tests were conducted to investigate the conventional properties and rheological properties of GTRSA. Moreover, the 2S2P1D (two springs, two parabolic elements, and one dashpot) model was adopted to analyze the consequences of adding GTR content on the rheological properties of GTRSA. Finally, the Pearson correlation coefficient was employed to reveal the connection between the conventional properties and the rheological properties. The results show that GTR has a great impact on improving the rutting resistance, thermo-sensitive performance, shear resistance capability, stress sensitivity, and creep recovery performance of GTRSA. Adding 20% GTR can improve the creep recovery rate to 80.8%. The 5 °C ductility index suggests that GTR makes a difference to the low-temperature properties. The rheological properties and conventional properties had a strong linear link.

CircSNX25 mediated by SP1 promotes the carcinogenesis and development of triple-negative breast cancer.

Circular RNAs (circRNAs), according to a growing body of research, are thought to be important in the initiation and development of a number of cancers. However, more research is needed to fully understand how circRNAs work at the molecular level in triple-negative breast cancer (TNBC). RNA sequencing was conducted on four sets of TNBC samples and their corresponding adjacent noncancerous tissues (ANTs). The circSNX25 expression was assessed using quantitative real-time PCR in TNBC tissues and cells. Several in vitro and in vivo experiments were conducted in order to examine the function of circSNX25 in TNBC carcinogenesis. Through luciferase reporter and chromatin immunoprecipitation (ChIP) assays, we also investigated the potential regulation of circSNX25 biogenesis by specificity protein 1 (SP1). To further validate the relationship between circSNX25 and COPI coat complex subunit beta 1 (COPB1) in TNBC, we conducted circRNA pull-down and RNA immunoprecipitation (RIP) assays using the MS2/MS2-CP system. Online databases were analyzed to examine the clinical implications and prognostic value of COPB1 in TNBC. A higher circSNX25 expression levels were observed in tissues and cells of TNBC. Silencing circSNX25 notably inhibited TNBC cell proliferation, triggered apoptosis, and hindered tumor growth in vivo. Conversely, upregulation of circSNX25 had the opposite effects. Mechanistically, circSNX25 was found to physically interact with COPB1. Importantly, we identified that SP1 may enhance circSNX25 biogenesis. COPB1 levels were markedly higher in TNBC cells. Analysis of online databases revealed that TNBC patients with elevated COPB1 levels had a poorer prognosis. Our findings demonstrate that SP1-mediated circSNX25 promotes TNBC carcinogenesis and development. CircSNX25 may therefore serve as both a diagnostic and therapeutic biomarker for TNBC patients.

Incidence and risk factors of fasting hyperglycaemia following first-attack acute pancreatitis before discharge: a retrospective study.

BACKGROUND: Pancreatic endocrine insufficiency is more likely to occur after acute pancreatitis (AP), but the risk factors affecting pancreatic endocrine function remain controversial. Therefore, exploring the incidence and risk factors of fasting hyperglycaemia following first-attack AP is important. METHODS: Data were collected from 311 individuals with first-attack AP without previous diabetes mellitus (DM) or impaired fasting glucose (IFG) history treated in the Renmin Hospital of Wuhan University. Relevant statistical tests were performed. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: The incidence of fasting hyperglycaemia in individuals with first-attack AP was 45.3%. Univariate analysis showed that age (χ2 = 6.27, P = 0.012), aetiology (χ2 = 11.184, P = 0.004), serum total cholesterol (TC) (χ2 = 14.622, P < 0.001), and serum triglyceride (TG) (χ2 = 15.006, P < 0.001) were significantly different between the hyperglycaemia and non-hyperglycaemia groups (P < 0.05). The serum calcium concentration (Z=-2.480, P = 0.013) was significantly different between the two groups (P < 0.05). Multiple logistic regression analysis showed that age- ≥60 years (P < 0.001, OR = 2.631, 95%Cl = 1.529-4.527) and TG ≥ 5.65 mmol/L (P < 0.001, OR = 3.964, 95%Cl = 1.990-7.895) were independent risk factors for fasting hyperglycaemia in individuals with first-attack AP (P < 0.05). CONCLUSIONS: Old age, serum triglycerides, serum total cholesterol, hypocalcaemia, and aetiology are associated with fasting hyperglycaemia following first-attack AP. Age ≥ 60 years and TG ≥ 5.65 mmol/L are independent risk factors for fasting hyperglycaemia following first-attack AP.

Evaluating the risk of knee osteoarthritis following unilateral ACL reconstruction based on an EMG-assisted method.

Objective: Anterior cruciate ligament reconstruction (ACLR) cannot decrease the risk of knee osteoarthritis after anterior cruciate ligament rupture, and tibial contact force is associated with the development of knee osteoarthritis. The purpose of this study was to compare the difference in bilateral tibial contact force for patients with unilateral ACLR during walking and jogging based on an EMG-assisted method in order to evaluate the risk of knee osteoarthritis following unilateral ACLR. Methods: Seven unilateral ACLR patients participated in experiments. The 14-camera motion capture system, 3-Dimension force plate, and wireless EMG test system were used to collect the participants' kinematics, kinetics, and EMG data during walking and jogging. A personalized neuromusculoskeletal model was established by combining scaling and calibration optimization. The inverse kinematics and inverse dynamics algorithms were used to calculate the joint angle and joint net moment. The EMG-assisted model was used to calculate the muscle force. On this basis, the contact force of the knee joint was analyzed, and the tibial contact force was obtained. The paired sample t-test was used to analyze the difference between the participants' healthy and surgical sides of the participants. Results: During jogging, the peak tibial compression force on the healthy side was higher than on the surgical side (p = 0.039). At the peak moment of tibial compression force, the muscle force of the rectus femoris (p = 0.035) and vastus medialis (p = 0.036) on the healthy side was significantly higher than that on the surgical side; the knee flexion (p = 0.042) and ankle dorsiflexion (p = 0.046) angle on the healthy side was higher than that on the surgical side. There was no significant difference in the first (p = 0.122) and second (p = 0.445) peak tibial compression forces during walking between the healthy and surgical sides. Conclusion: Patients with unilateral ACLR showed smaller tibial compression force on the surgical side than on the healthy side during jogging. The main reason for this may be the insufficient exertion of the rectus femoris and vastus medialis.

Regulation of Cx43 Gap Junction Intercellular Communication by Bruton's Tyrosine Kinase and Interleukin-2-Inducible T-Cell Kinase.

T and B cell receptor signaling involves the activation of Akt, MAPKs, and PKC as well as an increase in intracellular Ca2+ and calmodulin activation. While these coordinate the rapid turnover of gap junctions, also implicated in this process is Src, which is not activated as part of T and B cell receptor signaling. An in vitro kinase screen identified that Bruton's tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) phosphorylate Cx43. Mass spectroscopy revealed that BTK and ITK phosphorylate Cx43 residues Y247, Y265, and Y313, which are identical to the residues phosphorylated by Src. Overexpression of BTK or ITK in the HEK-293T cells led to increased Cx43 tyrosine phosphorylation as well as decreased gap junction intercellular communication (GJIC) and Cx43 membrane localization. In the lymphocytes, activation of the B cell receptor (Daudi cells) or T cell receptor (Jurkat cells) increased the BTK and ITK activity, respectively. While this led to increased tyrosine phosphorylation of Cx43 and decreased GJIC, the cellular localization of Cx43 changed little. We have previously identified that Pyk2 and Tyk2 also phosphorylate Cx43 at residues Y247, Y265, and Y313 with a similar cellular fate to that of Src. With phosphorylation critical to Cx43 assembly and turnover, and kinase expression varying between different cell types, there would be a need for different kinases to achieve the same regulation of Cx43. The work presented herein suggests that in the immune system, ITK and BTK have the capacity for the tyrosine phosphorylation of Cx43 to alter the gap junction function in a similar manner as Pyk2, Tyk2, and Src.

Constitutively activated AMPKα1 protects against skeletal aging in mice by promoting bone-derived IGF-1 secretion.

Senile osteoporosis is characterized by age-related bone loss and bone microarchitecture deterioration. However, little is known to date about the mechanism that maintains bone homeostasis during aging. In this study, we identify adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) as a critical factor regulating the senescence and lineage commitment of mesenchymal stem cells (MSCs). A phospho-mutant mouse model shows that constitutive AMPKα1 activation prevents age-related bone loss and promoted MSC osteogenic commitment with increased bone-derived insulin-like growth factor 1 (IGF-1) secretion. Mechanistically, upregulation of IGF-1 signalling by AMPKα1 depends on cAMP-response element binding protein (CREB)-mediated transcriptional regulation. Furthermore, the essential role of the AMPKα1/IGF-1/CREB axis in promoting aged MSC osteogenic potential is confirmed using three-dimensional (3D) culture systems. Taken together, these results can provide mechanistic insight into the protective effect of AMPKα1 against skeletal aging by promoting bone-derived IGF-1 secretion.

High-Entropy Alloy Aerogels: A New Platform for Carbon Dioxide Reduction.

High-entropy alloy aerogels (HEAAs) combined with the advantages of high-entropy alloys and aerogels are prospective new platforms in catalytic reactions. However, due to the differences in reduction potentials and miscibility behavior of different metals, the realization of HEAAs with a single phase is still a great challenge. Herein, a series of HEAAs is fabricated via the freeze-thaw method as highly active and durable electrocatalysts for the carbon dioxide reduction reaction (CO2 RR). Especially, the PdCuAuAgBiIn HEAAs can achieve Faradaic efficiency (FE) of C1 products almost 100% from -0.7 to -1.1 V versus reversible hydrogen electrode (VRHE ), and a maximum FE for formic acid (FEHCOOH ) of 98.1% at -1.1 VRHE , outperforming PdCuAuAgBiIn high-entropy alloy particles (HEAPs) and Pd metallic aerogels (MAs). Specifically, the current density and FEHCOOH are almost 200 mA cm-2 and 87% in a flow cell. The impressive CO2 RR performance of the PdCuAuAgBiIn HEAAs is attributed to the strong interactions between the different metals and the surface unsaturated sites, which can regulate the electronic structures of different metals and allow the optimal HCOO* intermediate adsorption and desorption onto the catalysts surface to enhance HCOOH production. The work not only provides a facile synthetic strategy to fabricate HEAAs, but also opens the avenue for development of efficient catalysts and beyond.