Summary Objective The purposes of this study were to assess whether local anesthetics (LAs), such as ropivacaine and bupivacaine, could induce apoptosis of rabbit annulus fibrosus (AF) cells in vitro ...and further to explore the possible underlying mechanism. Methods Rabbit AF cells at second passage were treated with saline solution and various concentrations of LAs. Apoptosis of AF cells were examined by cell counting kit-8 (CCK-8), Annexin V assays, Hoechst 33342 staining, and Caspase-3, -9 activity assays. The expression of apoptosis-related markers was detected by real-time PCR (RT-PCR) and Western Blot. The JC-1 staining was used to evaluate the change of mitochondrial membrane potential (MMP). Moreover, the levels of reactive oxygen species (ROS) were determined with fluorescent probe DCFH-DA. Results The results of flow cytometry indicated that LAs could induce apoptosis of rabbit AF cells in a dose-dependent manner. Apoptosis was confirmed by cell morphology, condensed nuclei and activation of Caspase-3 and -9. In addition, the molecular data showed that LAs could significantly up-regulate the expression of Bax, accompanied by a significant down-regulation of Bcl-2 expression. Furthermore, we also observed that LAs resulted in alteration of MMP and accumulation of intracellular ROS in AF cells. Blockade of ROS production by N-acetyl- l -cysteine (NAC) inhibited LAs-induced apoptosis. Conclusions These findings suggest that LAs in clinically relevant concentrations could induce apoptosis of rabbit AF cells in vitro , and the mitochondrial pathway was, at least in part, involved in the LAs-mediated apoptosis. Further investigations focusing on the potential cytotoxicity of LAs on IVD cells are needed.
Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% ...of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.
We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.
Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.
HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
High resolution angle-resolved photoemission spectroscopy data along the (0,0)-(pi,pi) nodal direction with significantly improved statistics reveal fine structure in the electron self-energy of the ...underdoped (La2-xSrx)CuO4 samples in the normal state. Fine structure at energies of (40-46) meV and (58-63) meV, and possible fine structure at energies of (23-29) meV and (75-85) meV, have been identified. These observations indicate that, in (La2-xSrx)CuO4, more than one bosonic modes are involved in the coupling with electrons.
Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been ...elucidated. Here we perform single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers. Secretome gene analysis revealed a highly connected network of intrahepatic signaling and disruption of vascular signaling in NASH. We uncovered the emergence of NASH-associated macrophages (NAMs), which are marked by high expression of triggering receptors expressed on myeloid cells 2 (Trem2), as a feature of mouse and human NASH that is linked to disease severity and highly responsive to pharmacological and dietary interventions. Finally, hepatic stellate cells (HSCs) serve as a hub of intrahepatic signaling via HSC-derived stellakines and their responsiveness to vasoactive hormones. These results provide unprecedented insights into the landscape of intercellular crosstalk and reprogramming of liver cells in health and disease.
Display omitted
•Heterogeneity and plasticity of non-parenchymal cells in healthy and NASH liver•Landscape of intrahepatic ligand-receptor signaling at single-cell resolution•Emergence of Trem2+ NASH-associated macrophages (NAMs) in mouse and human NASH•Stellakine secretion and contractile response to vasoactive hormones by HSCs
This work illustrates the heterogeneity of liver non-parenchymal cells (NPCs) and their reprogramming during NASH pathogenesis. Using single-cell RNA-sequencing analysis, the authors mapped the landscape of the intrahepatic ligand-receptor signaling network and revealed two fundamental aspects of HSC biology: stellakine secretion and contractile response to vasoactive hormones. Hepatic vascular dysfunction and emergence of Trem2+ NASH-associated macrophages (NAMs) are two conserved features of mouse and human NASH.
The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies ...targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.
•We prepared MoSe2 hollow microspheres by template-free hydrothermal process.•The MoSe2 hollow microspheres consist of nanosheets with diameters of ~1.5 μm.•The MoSe2 electrode achieves excellent Na+ ...storage performance as an anode for NIBs.
Molybdenum selenide has attracted considerable attention for sodium-ion batteries (SIBs) due to its excellent reactivity and large capacity compared to other transition metal dichalcogenides (TMDs). Herein, a facile template-free hydrothermal process is conducted to synthesize hierarchical MoSe2 hollow microspheres with the diameters of ~1.5 μm. The as-prepared MoSe2 hollow microspheres consist of cross-linked nanosheets. As an anode of SIBs, the hierarchical MoSe2 hollow microspheres exhibit a high initial discharge capacity of 710.2 mAh g−1. When the current density is as high as 1000 mA g−1, the specific capacity can still maintain at 290 mAh g−1. The excellent cycling performance and rate capability are due to the hollow microspherical architecture, which shortens the diffusion length of Na+, promotes the penetration of electrolyte into active materials and accommodates the volume stress. It is a successful case to obtain hollow architectures to shed some lights on the high-performance SIBs.
The mechanism that causes high-temperature superconductivity in copper oxide materials (cuprates) is still unknown, more than 15 years after it was discovered. As the charge carriers (electrons or ...holes) are introduced into the parent antiferromagnetic insulator, a process called doping, the material evolves from an insulator to a superconductor, and eventually to a normal metal. This marked change of physical properties with doping indicates that doping dependence (non-universality) might be a general feature of these materials, but we find that, on the contrary, the low-energy Fermi velocity of electrons is in fact universal, even among different superconductor families.
The mechanism of the charge density wave transition in quasi one-dimensional blue bronzes is still debated. Here, the authors report evidence of a Luttinger liquid in the normal state of blue bronzes ...and Holstein polarons below the transition temperature, revealing the important role of electron-phonon coupling in the transition.
PDF
