Regulated necrosis (necroptosis) and apoptosis are crucially involved in severe cardiac pathological conditions, including myocardial infarction, ischemia-reperfusion injury and heart failure. ...Whereas apoptotic signaling is well defined, the mechanisms that underlie cardiomyocyte necroptosis remain elusive. Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca(2+)-calmodulin-dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL. In mice, RIP3 deficiency or CaMKII inhibition ameliorates myocardial necroptosis and heart failure induced by ischemia-reperfusion or by doxorubicin treatment. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. These findings identify CaMKII as a new RIP3 substrate and delineate a RIP3-CaMKII-mPTP myocardial necroptosis pathway, a promising target for the treatment of ischemia- and oxidative stress-induced myocardial damage and heart failure.
Transition metal silicides are promising advanced functional materials. However, the structure and relevant properties of Mo5Si3 are not well understood. In this work, we investigate the crystal ...structure, elastic properties, Vickers hardness, elastic anisotropy, electronic and thermodynamic properties of Mo5Si3 by using the first-principles calculations. Three structures: tetragonal, hexagonal and orthorhombic structures are considered. The calculated results show that those structures are thermodynamically stable. In particular, we firstly predict that Mo5Si3 with hexagonal (P63/mcm) structure is a stable phase. The calculated electronic structure shows that Mo5Si3 exhibits better electronic properties because of the charge overlap between Mo-4d state and Si-3p state near the Fermi level. Importantly, Mo5Si3 shows the strong deformation resistance and high elastic stiffness in comparison to other TM5Si3. Mo5Si3 with tetragonal structure has the smaller percentage anisotropy in compressibility and high percentage anisotropy in shear. We further find that the Debye temperature and heat capacity of tetragonal structure are larger than that of hexagonal structure. The high-temperature thermodynamic properties of Mo5Si3 are attributed to the vibration of Si atom.
•MiR-146b, highly expressed in mature adipocytes while lowly in human mesenchymal stem cells and visceral preadipocytes.•Gain-and loss-of-function studies indicated that miR-146b could affect ...visceral adipogenesis.•MiR-146b in human visceral adipocytes could inhibit both of KLF7 mRNA and protein levels.•Firefly luciferase reporter assay proved that KLF7 was a direct target of miR-146b in human visceral adipocytes.•MiR-146b expression was significantly altered in adipose tissues of human obesity and DIO mice.
Visceral obesity is an independent risk factor for metabolic syndrome, and abnormal fat accumulation is linked to increases in the number and size of adipocytes. MiR-146b was a miRNA highly expressed in mature adipocytes while very lowly expressed in human mesenchymal stem cells (hMSCs) and human visceral preadipocytes (vHPA). In this paper, we mainly focused on the roles of miR-146b in adipogenesis. We found miR-146b could inhibit the proliferation of visceral preadipocytes and promote their differentiation. MiR-146b in human visceral adipocytes inhibited the expression of KLF7, a member of the Kruppel-like transcription factors, as demonstrated by a firefly luciferase reporter assay, indicating that KLF7 is a direct target of the endogenous miR-146b. MiR-146b expression was significantly altered in visceral and subcutaneous adipose tissues in human overweight and obese subjects, and in the epididymal fat tissues and brown fat tissues of diet-induced obese mice. Our data indicates that miR-146b may be a new therapeutic target against human visceral obesity and metabolic dysfunction.
The aqueous zinc‐ion battery is promising as grid scale energy storage device, but hindered by the instable electrode/electrolyte interface. Herein, we report the lean‐water ionic liquid electrolyte ...for aqueous zinc metal batteries. The lean‐water ionic liquid electrolyte creates the hydrophobic tri‐layer interface assembled by first two layers of hydrophobic OTF− and EMIM+ and third layer of loosely attached water, beyond the classical Gouy–Chapman–Stern theory based electrochemical double layer. By taking advantage of the hydrophobic tri‐layer interface, the lean‐water ionic liquid electrolyte enables a wide electrochemical working window (2.93 V) with relatively high zinc ion conductivity (17.3 mS/cm). Furthermore, the anion crowding interface facilitates the OTF− decomposition chemistry to create the mechanically graded solid electrolyte interface layer to simultaneously suppress the dendrite formation and maintain the mechanical stability. In this way, the lean‐water based ionic liquid electrolyte realizes the ultralong cyclability of over 10000 cycles at 20 A/g and at practical condition of N/P ratio of 1.5, the cumulated areal capacity reach 1.8 Ah/cm2, which outperforms the state‐of‐the‐art zinc metal battery performance. Our work highlights the importance of the stable electrode/electrolyte interface stability, which would be practical for building high energy grid scale zinc‐ion battery.
An electrochemical hydrophobic tri‐layer interface is developed through the lean‐water ionic liquid electrolyte design to create stable electrode/electrolyte interface. The OTF‐ rich interface facilitates the formation of mechanically graded solid electrolyte interface. As a result, the lean‐water ionic liquid electrolyte enabled zinc metal battery stable operation at practical condition and under wide temperature range.
Aims and objectives
To observe the effects of bundle care on preventing unplanned extubation of nasobiliary drainage catheter after endoscopic retrograde cholangiopancreatography.
Background
...Preventing unplanned extubation has become a difficult problem for nursing staff because the catheter is stiff, fine and long.
Design
A total of 114 cases that experienced nasobiliary drainage after endoscopic retrograde cholangiopancreatography for the first time in our hospital from April 2015–July 2016 were enrolled in this study. According to receiving routine nurse or bundle nurse, these cases were randomly divided into control (n = 56) and intervention (n = 58) group.
Method
The unplanned extubation incidence, contact area between tape and catheter and tensile resistance were compared between the two groups.
Results
The contact area was one square centimetre in the control group and 5 cm2 in the intervention group. Tensile resistance was significantly higher in the intervention group than in the control (all p < .05). Unplanned extubation incidence was significantly lower in the intervention group (1.72%, 1/58) than in the control (12.5%, 7/56) (p = .0305).
Conclusion
Bundle care can effectively decrease unplanned extubation incidence after endoscopic retrograde cholangiopancreatography.
Relevance to clinical practice
This study provides a basis for decreasing unplanned extubation incidence.
Objectives
It has been proven that extracellular HMGB1 is involved in progression of neurologic disorders, such as stroke, traumatic brain injury, meningitis and epilepsy. Glycyrrhizin (GL) is a ...direct inhibitor of HMGB1, and blocks HMGB1 release into the extracellular. We aim in this study to investigate the neuroprotective effects of GL in a rat model after lithium‐pilocarpine‐induced status epilepticus (SE).
Methods
Adult male SD rats were divided into three groups: Sham group, SE‐group and (SE + GL)‐treated group. The HMGB1 expression in serum and hippocampus, the damage extent of blood brain barrier (BBB) and hippocampal neuronal damage were evaluated by enzyme‐linked immunosorbent assay, immunohistochemistry, western blot and nissl's staining.
Key findings
Glycyrrhizin markedly reduced HMGB1 expression in serum and hippocampus, prevented HMGB1 translocation from nucleus to cytoplasm in hippocampal CA1, CA3 and hilus areas of SE rats. Meanwhile, GL significantly ameliorated neuronal damage in the CA1, CA3 and hilus areas of hippocampus, and protected BBB disruption after SE. The administration of GL significantly decreased the mortality from 25 to 8.9% in rats.
Conclusions
Glycyrrhizin may exert neuroprotective effects via inhibiting HMGB1 and protect BBB permeability in lithium‐pilocarpine‐induced rats with SE.
Uncontrollable zinc dendrite growth and parasitic reactions have greatly hindered the development of high energy and long life rechargeable aqueous zinc‐ion batteries. Herein, the synergic effect of ...a bifunctional lignin‐containing cellulose nanofiber (LCNF)‐MXene (LM) layer to stabilize the interface of zinc anode is reported. On one hand, the LCNF provides enough strength (43.7 MPa) at relative low porosity (52.2%) to enable the diffusion limited dendrite suppression, while, on the other hand, the MXene serves as a zinc gating layer, facilitating the zinc ion mobility, restricting the active water/anions from degradation in the electrode/electrolyte interface, and epitaxially guiding zinc deposition along (002) plane. Benefiting from the synergic effect of diffusion limited dendrite suppression and zinc gate, the LM layer enabled a high coulombic efficiency (CE) of 98.9% with a low overpotential of 43.1 mV at 1 mA cm−2 in Zn//Cu asymmetric cells. More importantly, Zn//MnO2 full cells with the LM layer achieve a high‐capacity retention of 90.0% for over 1000 cycles at 1 A g−1, much higher than the full cell without the protective layer (73.9% over 500 cycles). The work provides a new insight in designing a dendrite‐free zinc anode for long‐cycle‐life batteries.
The synergic effect of mechanical induced dendrite suppression and zinc gating layer to enable corrosion‐free zinc anode for long‐cycle‐life batteries with the lignin‐containing cellulose nanofiber (LCNF)‐MXene layer is implemented, in which LCNFs act as a desolvation layer to suppress water‐induced corrosion reactions while the MXene serves as a zinc gating layer to guide dendrite formation in the lateral direction.
An effective post-processing algorithm is essential for achieving high rates of secret key generation in quantum key distribution. This work introduces an approach to quantum key distribution ...post-processing by integrating the three main steps into a unified procedure: syndrome-based error estimation, rate-adaptive reconciliation, and subblock confirmation. The proposed scheme employs low-density parity-check codes to estimate the quantum bit error rate using the syndrome information, and to optimize the channel coding rates based on the Slepian-Wolf coding scheme for the rate-adaptive method. Additionally, this scheme incorporates polynomial-based hash verification in the subblock confirmation process. The numerical results show that the syndrome-based estimation significantly enhances the accuracy and consistency of the estimated quantum bit error rate, enabling effective code rate optimization for rate-adaptive reconciliation. The unified approach, which integrates rate-adaptive reconciliation with syndrome-based estimation and subblock confirmation, exhibits superior efficiency, minimizes practical information leakage, reduces communication rounds, and guarantees convergence to the identical key. Furthermore, the simulations indicate that the secret key throughput of this approach achieves the theoretical limit in the context of a BB84 quantum key distribution system.
We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade ...immunotherapies in this disease setting.
A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues.
At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, 'immuno-active', 'immuno-medial', 'immuno-NK', and 'immuno-deficient'. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention.
A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic.
The induced death signals following oncogene inhibition underlie clinical efficacy of molecular targeted therapies against human cancer, and defects of intact cell apoptosis machinery often lead to ...therapeutic failure. Despite potential importance, other forms of regulated cell death triggered by pharmacologic intervention have not been systematically characterized.
Pyroptotic cell death was assessed by immunoblot analysis, phase-contrast imaging, scanning electron microscopy, and flow cytometry. Tumor tissues of patients with lung cancer were analyzed using IHC. Functional impact of pyroptosis on drug response was investigated in cell lines and xenograft models.
We showed that diverse small-molecule inhibitors specifically targeting KRAS-, EGFR-, or ALK-driven lung cancer uniformly elicited robust pyroptotic cell death, in addition to simultaneously invoking cellular apoptosis. Upon drug treatment, the mitochondrial intrinsic apoptotic pathway was engaged and the mobilized caspase-3 protease cleaved and activated gasdermin E (GSDME, encoded by
), which permeabilized cytoplasmic membrane and executed cell-lytic pyroptosis. GSDME displayed ubiquitous expression in various lung cancer cell lines and clinical specimens, including
-mutant,
-altered, and
-rearranged adenocarcinomas. As a result, cooccurrence and interplay of apoptosis and pyroptosis were widespread in lung cancer cells, succumbing to genotype-matched regimens. We further demonstrated that pyroptotic cell death partially contributed to the drug response in a subset of cancer models.
These results pinpoint GSDME-dependent pyroptosis as a previously unrecognized mechanism of action for molecular targeted agents to eradicate oncogene-addicted neoplastic cells, which may have important implications for the clinical development and optimal application of anticancer therapeutics.
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