Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence

<p>Abstract</p> <p>Background</p> <p>Cide family proteins including Cidea, Cideb and Cidec/Fsp27, contain an N-terminal CIDE-N domain that shares sequence similarity to the N-terminal CAD domain (NCD) of DNA fragmentation factors Dffa/Dff45/ICAD and Dffb/Dff40/CAD, and a unique C-terminal CIDE-C domain. We have previously shown that Cide proteins are newly emerged regulators closely associated with the development of metabolic diseases such as obesity, diabetes and liver steatosis. They modulate many metabolic processes such as lipolysis, thermogenesis and TAG storage in brown adipose tissue (BAT) and white adipose tissue (WAT), as well as fatty acid oxidation and lipogenesis in the liver.</p> <p>Results</p> <p>To understand the evolutionary process of Cide proteins and provide insight into the role of Cide proteins as potential metabolic regulators in various species, we searched various databases and performed comparative genomic analysis to study the sequence conservation, genomic structure, and phylogenetic tree of the CIDE-N and CIDE-C domains of Cide proteins. As a result, we identified signature sequences for the N-terminal region of Dffa, Dffb and Cide proteins and CIDE-C domain of Cide proteins, and observed that sequences homologous to CIDE-N domain displays a wide phylogenetic distribution in species ranging from lower organisms such as hydra (<it>Hydra vulgaris</it>) and sea anemone (<it>Nematostella vectensis</it>) to mammals, whereas the CIDE-C domain exists only in vertebrates. Further analysis of their genomic structures showed that although evolution of the ancestral CIDE-N domain had undergone different intron insertions to various positions in the domain among invertebrates, the genomic structure of <it>Cide </it>family in vertebrates is stable with conserved intron phase.</p> <p>Conclusion</p> <p>Based on our analysis, we speculate that in early vertebrates CIDE-N domain was evolved from the duplication of NCD of Dffa. The CIDE-N domain somehow acquired the CIDE-C domain that was formed around the same time, subsequently generating the Cide protein. Subsequent duplication and evolution have led to the formation of different Cide family proteins that play unique roles in the control of metabolic pathways in different tissues.</p

Of Natural Killer cells and Hepatitis C Virus

Natural Killer (NK) cells are important effector cells in Hepatitis C Virus (HCV) infection, a virus that chronically infects around 2.5% of the world population and is a major cause of liver disease and hepatocellular carcinoma. The exact mechanisms, however, through which NK cells are activated in response to HCV remain elusive. Using the well-established HCV replicon cell-culture model we show that after co- culture of HCV replicon-carrying hepatocytes with peripheral blood mononuclear cells (PBMCs), NK cells increase expression of the high-affinity IL-2 receptor chain CD25, proliferate rapidly and produce IFN-gamma. Activation of NK cells was dependent on IL-2, most likely produced by T cells and on cell-cell contact mediated signals from monocytes. Monocytes from replicon-carrying co-cultures showed increased expression of OX40L, a member of the tumor necrosis factor family and concurrently its receptor OX40 was increased on NK cells. Blocking of OX40L in those co-cultures, as well as depletion of CD14+ monocytes abrogated the virus-induced activation and effector functions of NK cells. Together, our data reveals a novel mechanism of monocyte mediated NK cell activation against virus-infected cells involving the OX40/OX40L axis with potential relevance for therapeutic intervention by e.g. agonistic antibodies against OX40, which are already tested in cancer therapy

Holistic Strategies Lead to Enhanced Efficiency and Stability of Hybrid Chemical Vapor Deposition Based Perovskite Solar Cells and Modules

Hybrid chemical vapor deposition (HCVD) is a promising method for the up-scalable fabrication of perovskite solar cells/modules (PSCs/PSMs). However, the efficiency of the HCVD-based perovskite solar cells still lags behind the solution-processed PSCs/PSMs. In this work, the oxygen loss of the electron transport layer of SnO2 in the HCVD process and its negative impact on solar cell device performance are revealed. As the counter-measure, potassium sulfamate (H2KNO3S) is introduced as the passivation layer to both mitigate the oxygen loss issue of SnO2 and passivate the uncoordinated Pb2+ in the perovskite film. In parallel, N-methylpyrrolidone (NMP) is used as the solvent to dissolve PbI2 by forming the intermediate phase of PbI2•NMP, which can greatly lower the energy barrier for perovskite nucleation in the HCVD process. The perovskite seed is employed to further modulate the kinetics of perovskite crystal growth and improve the grain size. The resultant solar cells yield a champion power conversion efficiency (PCE) of 21.98% (0.09 cm2) with a stable output performance of 21.15%, and the PCEs of the mini-modules are 16.16% (22.4 cm2, stable output performance of 14.72%) and 12.12% (91.8 cm2). Furthermore, the unencapsulated small area device shows an outstanding operational stability with a T80 lifetime exceeding 4000 h.journal articl

Constructing Heterostructure through Bidentate Coordination toward Operationally Stable Inverted Perovskite Solar Cells

It has been reported that one of the influencing factors leading to stability issues in iodine-containing perovskite solar cells is the iodine loss from the perovskite layer. Herein, bidentate coordination is used with undercoordinated I− of the perovskite surface to construct the stable perovskite-based heterostructure. This strong halogen bonding effectively inhibits interfacial migration of I− into functional layers such as C60 and Ag. Moreover, passivation of the undercoordinated I− suppresses the release of I2 and further delays the formation of voids at the perovskite surface. The resulting inverted perovskite solar cell exhibits a power conversion efficiency of 22.59% and the unencapsulated device maintains 96.15% of its initial value after continuous operation for 500 h under illumination.journal articl

Graphene‐Like Conjugated Molecule as Hole‐Selective Contact for Operationally Stable Inverted Perovskite Solar Cells and Modules

Further enhancing the operational lifetime of inverted-structure perovskite solar cells (PSCs) is crucial for their commercialization, and the design of hole-selective contacts at the illumination side plays a key role in operational stability. In this work, the self-anchoring benzo[rst]pentaphene (SA-BPP) is developed as a new type of hole-selective contact toward long-term operationally stable inverted PSCs. The SA-BPP molecule with a graphene-like conjugated structure shows a higher photostability and mobility than that of the frequently-used triphenylamine and carbazole-based hole-selective molecules. Besides, the anchoring groups of SA-BPP promote the formation of a large-scale uniform hole contact on ITO substrate and efficiently passivate the perovskite absorbers. Benefiting from these merits, the champion efficiencies of 22.03% for the small-sized cells and 17.08% for 5 × 5 cm2 solar modules on an aperture area of 22.4 cm2 are achieved based on this SA-BPP contact. Also, the SA-BPP-based device exhibits promising operational stability, with an efficiency retention of 87.4% after 2000 h continuous operation at the maximum power point under simulated 1-sun illumination, which indicates an estimated T80 lifetime of 3175 h. This novel design concept of hole-selective contacts provides a promising strategy for further improving the PSC stability.journal articl

Elimination of light-induced degradation at the nickel oxide-perovskite heterojunction by aprotic sulfonium layers towards long-term operationally stable inverted perovskite solar cells

Nickel oxide (NiOx) is a promising hole-selective contact to produce efficient inverted p-i-n structured perovskite solar cells (PSCs) due to its high carrier mobility and high transparency. However, the light-induced degradation of the NiOx–perovskite heterojunction is the main factor limiting its long-term operational lifetime. In this study, we used the time-resolved mass spectrometry technique to clarify the degradation mechanism of the NiOx-formamidinium–methylammonium iodide perovskite (a common composition for high-performance PSCs) heterojunction under operational conditions, and observed that (1) oxidation of iodide and generation of free protons under 1-sun illumination, (2) formation of volatile hydrogen cyanide, methyliodide, and ammonia at elevated temperatures, and (3) a condensation reaction between the organic components under a high vapor pressure. To eliminate these multi-step photochemical reactions, we constructed an aprotic trimethylsulfonium bromide (TMSBr) buffer layer at the NiOx/perovskite interface, which enables excellent photo-thermal stability, a matched lattice parameter with the perovskite crystal, and robust trap-passivation ability. Inverted PSCs stabilized with the TMSBr buffer layer reached the maximum efficiency of 22.1% and retained 82.8% of the initial value after continuous operation for 2000 hours under AM1.5G light illumination, which translates into a T80 lifetime of 2310 hours that is among the highest operational lifetimes for NiOx-based PSCs

Preliminary Efficacy of a Cognitive Behavioral Therapy–Based Smartphone App for Smoking Cessation in China: Randomized Controlled Pilot Trial

BackgroundThe overall prevalence of cigarette smokers in China is very high, and China’s total cigarette consumption makes up more than 40% of the world’s consumption. In view of the lack of smoking cessation services and social support in China and the effectiveness of mobile phone apps for quitting smoking in other countries, we carried out a smartphone app–based smoking cessation trial in China. ObjectiveThis study aimed to evaluate the efficacy of a cognitive behavioral therapy (CBT)–based smoking cessation smartphone app among smokers seeking treatment in China. MethodsWe conducted a randomized controlled, web-based pilot clinical trial in China between February 23 and June 27, 2021. Eligible participants were randomly assigned to the smoking cessation app intervention group or the control group in a ratio of 1:1. The intervention group received the CBT smoking cessation intervention using a smartphone app, and the control group received a “thank you” message. The intervention was 4 weeks long, and the patients were followed up for 4 weeks. The primary outcome was self-reported continuous smoking abstinence at week 4 after the quit date. The secondary outcomes included self-reported 7-day point prevalence of smoking abstinence; reduction of the number of cigarettes smoked per day at weeks 1, 2, 3, and 4; and program acceptability. ResultsA total of 973 people were recruited to quit smoking, of whom 262 completed basic information, 56 were excluded, and 206 were randomized and included in the final analysis. There were 189 (91.7%) men and 17 (8.3%) women, with an average age of 34.46 (SD 7.53) years and an average daily smoking rate of 15.93 (SD 7.10) cigarettes/day. We found 30 (29.7%) of the 101 participants in the intervention group and 7 (6.7%) of the 105 participants in the control group reported continuous smoking cessation after the quit date at week 4 (odds ratio 5.92, 95% CI 3.78-9.26; P<.001). The 7-day point prevalence abstinence rate of the intervention group varied from 42.6% (43/101) to 46.5% (47/101) after 1, 2, 3, and 4 weeks, while the control group varied from 18.1% (19/105) to 26.7% (28/105). Compared to the control group, continued smokers consumed 1.5-3.0 fewer cigarettes per day in the intervention group. The overall program got positive user feedback with a high satisfaction rate (66/87, 76%) and an average Mobile Application Rating Scale user version score of 3.46. ConclusionsOur pilot study provided preliminary evidence that the CBT-based smoking cessation smartphone app led to improved smoking quit rates versus control in Chinese smokers. The study demonstrated the CBT-based smartphone app may be an effective and feasible digital treatment model to help smokers quit, which may improve smoking cessation service quality and accessibility in China. Trial RegistrationClinicalTrials.gov NCT04421170; https://clinicaltrials.gov/study/NCT04421170 International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2020-04198

Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence-5

Algorithm. The CIDE-N domain is indicated by a dark line on top of the alignment. The alignment of the most conserved region of 37 amino acids encompassing the EDGT signature motif is framed with a red rectangle. The signatures of Cide and Dff family proteins are framed with a green rectangle. The exon boundaries are marked by black vertical lines. (B) Sequence alignment of the CIDE-C domains of Cide family proteins found in human and mouse using MAFFT algorithm. The CIDE-C domain is indicated by a dark line on top of the alignment. The alignment of most conserved 35 amino acids is framed with a red rectangle. The exon boundaries are marked by black vertical lines.<p><b>Copyright information:</b></p><p>Taken from "Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence"</p><p>http://www.biomedcentral.com/1471-2148/8/159</p><p>BMC Evolutionary Biology 2008;8():159-159.</p><p>Published online 23 May 2008</p><p>PMCID:PMC2426694.</p><p></p

Rapid and effective treatment of chronic osteomyelitis by conductive network-like MoS2/CNTs through multiple reflection and scattering enhanced synergistic therapy

Staphylococcus aureus (S. aureus)-infected chronic osteomyelitis (COM) is one of the most devastating infectious diseases with a high recurrence rate, often leading to amputation and even death. It is incurable by all the current strategies involving the clinical use of radical debridement and systemic intravenous antibiotics. Here, we reported on a microwave (MW)-assisted therapy for COM by constructing a heterojunction formed by flake nanoflower-shaped molybdenum disulfide (MoS2) and tubular carbon nanotubes (CNTs). This composite could achieve a combination of MW thermal therapy (MTT) and MW dynamic therapy (MDT) to accurately and rapidly treat COM with deep tissue infection. In vitro and in vivo experiments showed that MoS2/CNTs were effective in non-invasively treating S. aureus-induced COM due to the heat and reactive oxygen species (ROS) produced under MW irradiation. The mechanism of heat and ROS generation was explained by MW network vector analysis, density of states (DOS), oxygen adsorption energy, differential charge and finite element (FEM) under MW irradiation. Since the Fermi layer was mainly contributed by the Mo-4d and C–2P orbitals, MoS2/CNTs could store a large amount of charge and easily release more electrons. In addition, charge accumulation and dissipation motion were strong on the surface of and inside MoS2/CNTs because of electromagnetic hot spots, resulting in the spilling out of a great deal of high-energy electrons. Due to the low oxygen adsorption energy of MoS2/CNTs-O2, these high-energy electrons combined further with the adsorbed oxygen to produce ROS