CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein-protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14-CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Efficient and Bright Organic Radical Light-Emitting Diodes with Low Efficiency Roll-Off.

Organic radicals have been of interest due to their potential to replace nonradical-based organic emitters, especially for deep-red/near-infrared (NIR) electroluminescence (EL), based on the spin-allowed doublet fluorescence. However, the performance of the radical-based EL devices is limited by low carrier mobility which causes a large efficiency roll-off at high current densities. Here, highly efficient and bright doublet EL devices are reported by combining a thermally activated delayed fluorescence (TADF) host that supports both electron and hole transport and a tris(2,4,6-trichlorophenyl)methyl-based radical emitter. Steady-state and transient photophysical studies reveal the optical signatures of doublet luminescence mechanisms arising from both host and guest photoexcitation. The host system presented here allows balanced hole and electron currents, and a high maximum external quantum efficiency (EQE) of 17.4% at 707 nm peak emission with substantially improved efficiency roll-off is reported: over 70% of the maximum EQE (12.2%) is recorded at 10 mA cm-2 , and even at 100 mA cm-2 , nearly 50% of the maximum EQE (8.4%) is maintained. This is an important step in the practical application of organic radicals to NIR light-emitting devices.

Bright and stable perovskite light-emitting diodes in the near-infrared range.

Perovskite light-emitting diodes (LEDs) have attracted broad attention due to their rapidly increasing external quantum efficiencies (EQEs)1-15. However, most high EQEs of perovskite LEDs are reported at low current densities (<1 mA cm-2) and low brightness. Decrease in efficiency and rapid degradation at high brightness inhibit their practical applications. Here, we demonstrate perovskite LEDs with exceptional performance at high brightness, achieved by the introduction of a multifunctional molecule that simultaneously removes non-radiative regions in the perovskite films and suppresses luminescence quenching of perovskites at the interface with charge-transport layers. The resulting LEDs emit near-infrared light at 800 nm, show a peak EQE of 23.8% at 33 mA cm-2 and retain EQEs more than 10% at high current densities of up to 1,000 mA cm-2. In pulsed operation, they retain EQE of 16% at an ultrahigh current density of 4,000 mA cm-2, along with a high radiance of more than 3,200 W s-1 m-2. Notably, an operational half-lifetime of 32 h at an initial radiance of 107 W s-1 m-2 has been achieved, representing the best stability for perovskite LEDs having EQEs exceeding 20% at high brightness levels. The demonstration of efficient and stable perovskite LEDs at high brightness is an important step towards commercialization and opens up new opportunities beyond conventional LED technologies, such as perovskite electrically pumped lasers.

Non-collinear magnetic configuration mediated exchange coupling at the interface of antiferromagnet and rare-earth nanolayers.

Mn[Formula: see text]Ir/CoFe bilayer is a prototypical exchange-coupled antiferromagnet (AF)-ferromagnet (FM) system. Nevertheless, a strong exchange coupling between FM and rare-earth(RE) interfaces of Fe/Dy and Fe/Tb has been established earlier. Strong coupling at the FM-RE interface originates from the number of irreversible spins owing to the imbalance in the non-collinear configuration in RE. However, exchange coupling between AF-RE could not be established due to the minimal number of irreversible spins in AF and RE. A frustrated inter-domain magnetic interaction leads to the coexistence of spin-freezing-like ordering around the temperature range of helical spin modulation at the exchange-coupled interfaces of RE-based specimens. To overcome the lack of coupling between the AF-RE interface, we use a sandwich structure of AF-FM-RE layers (Mn[Formula: see text]Ir/CoFe/Dy) as we demonstrate establishing considerable exchange bias in the system. Changing the bias direction during field cooling introduces possible differences in non-collinear directions (helicities), which affects the number of irreversible spins and consequent exchange coupling differently for opposite directions. The non-collinear structures in RE are topologically stable; thus, their directions of orientation can be regarded as an additional degree of freedom, which can be manipulated in all-spin-based technology.

Efficient vertical charge transport in polycrystalline halide perovskites revealed by four-dimensional tracking of charge carriers.

Fast diffusion of charge carriers is crucial for efficient charge collection in perovskite solar cells. While lateral transient photoluminescence microscopies have been popularly used to characterize charge diffusion in perovskites, there exists a discrepancy between low diffusion coefficients measured and near-unity charge collection efficiencies achieved in practical solar cells. Here, we reveal hidden microscopic dynamics in halide perovskites through four-dimensional (directions x, y and z and time t) tracking of charge carriers by characterizing out-of-plane diffusion of charge carriers. By combining this approach with confocal microscopy, we discover a strong local heterogeneity of vertical charge diffusivities in a three-dimensional perovskite film, arising from the difference between intragrain and intergrain diffusion. We visualize that most charge carriers are efficiently transported through the direct intragrain pathways or via indirect detours through nearby areas with fast diffusion. The observed anisotropy and heterogeneity of charge carrier diffusion in perovskites rationalize their high performance as shown in real devices. Our work also foresees that further control of polycrystal growth will enable solar cells with micrometres-thick perovskites to achieve both long optical path length and efficient charge collection simultaneously.

c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance.

Acute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia characterized by unrestricted megakaryoblast proliferation and poor prognosis. Thrombopoietin receptor c-Mpl is a primary regulator of megakaryopoeisis and a potent mitogenic receptor. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however, the role of c-Mpl in AMKL progression remains largely unexplored. Here, we identified increased expression of a c-Mpl alternative splicing isoform, c-Mpl-del, in AMKL patients. We found that c-Mpl-del expression was associated with enhanced AMKL cell proliferation and chemoresistance, and decreased survival in xenografted mice, while c-Mpl-del knockdown attenuated proliferation and restored apoptosis. Interestingly, we observed that c-Mpl-del exhibits preferential utilization of phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in upregulation of GATA1 and downregulation of DDIT3-related apoptotic responses conducive to AMKL chemoresistance and proliferation. Thus, this study elucidates the critical roles of c-Mpl alternative splicing in AMKL progression and drug resistance, which may have important diagnostic and therapeutic implications for leukemia accelerated by c-Mpl-del overexpression.

Influences of dielectric constant and scan rate on hysteresis effect in perovskite solar cell with simulation and experimental analyses.

In this work, perovskite solar cells (PSCs) with different transport layers were fabricated to understand the hysteresis phenomenon under a series of scan rates. The experimental results show that the hysteresis phenomenon would be affected by the dielectric constant of transport layers and scan rate significantly. To explain this, a modified Poisson and drift-diffusion solver coupled with a fully time-dependent ion migration model is developed to analyze how the ion migration affects the performance and hysteresis of PSCs. The modeling results show that the most crucial factor in the hysteresis behavior is the built-in electric field of the perovskite. The non-linear hysteresis curves are demonstrated under different scan rates, and the mechanism of the hysteresis behavior is explained. Additionally, other factors contributing to the degree of hysteresis are determined to be the degree of degradation in the perovskite material, the quality of the perovskite crystal, and the materials of the transport layer, which corresponds to the total ion density, carrier lifetime of perovskite, and the dielectric constant of the transport layer, respectively. Finally, it was found that the dielectric constant of the transport layer is a key factor affecting hysteresis in perovskite solar cells.

A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.

Real-time observation of nucleation and growth of Au on CdSe quantum dot templates.

Semiconductor quantum dot (QD) arrays can be useful for optical devices such as lasers, solar cells and light-emitting diodes. As the size distribution influences the band-gap, it is worthwhile to investigate QDs prepared using different solvents because each of them could influence the overall morphology differently, depending on the ligand network around individual QDs. Here, we follow the nucleation and growth of gold (Au) on CdSe QD arrays to investigate the influence of surface ligands and thereby realized interparticle distance between QDs on Au growth behaviour. We particularly emphasize on the monolayer stage as the Au decoration on individual QDs is expected at this stage. Therefore, we sputter-deposit Au on each QD array to investigate the morphological evolution in real-time using time-resolved grazing-incidence small-angle X-ray scattering (GISAXS). The growth kinetics - independent of the template - signifies that the observed template-mediated nucleation is limited only to the very first few monolayers. Delicate changes in the Au growth morphology are seen in the immediate steps following the initial replicated decoration of the QD arrays. This is followed by a subsequent clustering and finally a complete Au coverage of the QD arrays.

SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation. METHODS: SARS-CoV-2 spike pseudovirions (SCV-2-S) were generated using the spike-expressing virus packaging system. Western blot, mCherry-GFP-LC3 labeling, immunofluorescence, and RNA-seq were performed to examine the regulatory mechanism of SCV-2-S in autophagic response. The effects of SCV-2-S on apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Western blot, and flow cytometry analysis. Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the mechanism of SCV-2-S in inflammatory responses. RESULTS: Angiotensin-converting enzyme 2 (ACE2)-mediated SCV-2-S infection induced autophagy and apoptosis in human bronchial epithelial and microvascular endothelial cells. Mechanistically, SCV-2-S inhibited the PI3K/AKT/mTOR pathway by upregulating intracellular reactive oxygen species (ROS) levels, thus promoting the autophagic response. Ultimately, SCV-2-S-induced autophagy triggered inflammatory responses and apoptosis in infected cells. These findings not only improve our understanding of the mechanism underlying SARS-CoV-2 infection-induced pathogenic inflammation but also have important implications for developing anti-inflammatory therapies, such as ROS and autophagy inhibitors, for COVID-19 patients.

EGFR-rich extracellular vesicles derived from highly metastatic nasopharyngeal carcinoma cells accelerate tumour metastasis through PI3K/AKT pathway-suppressed ROS.

Nasopharyngeal carcinoma (NPC) is the most common cancer with high metastatic potential that occurs in the epithelial cells of the nasopharynx. Distant metastases are the primary cause for treatment failure and mortality of NPC patients. However, the underlying mechanism responsible for the initiation of tumour cell dissemination and tumour metastasis in NPC is not well understood. Here, we demonstrated that epidermal growth factor receptor (EGFR) was highly expressed in tumour tissues of NPC patients with distant metastases and was associated with a decrease in reactive oxygen species (ROS). We also revealed that extracellular vesicles (EVs) transfer occurred from highly to poorly metastatic NPC cells, mediating cell-cell communication and enhancing the metastatic potential of poorly metastatic NPC cells. Further experiments indicated that EVs derived from highly metastatic NPC cells induced the up-regulation of EGFR and down-regulation of ROS in low metastatic NPC cells. Mechanistically, EGFR-rich EVs-mediated EGFR overexpression down-regulated intracellular ROS levels through the PI3K/AKT pathway, thus promoting the metastatic potential of poorly metastatic NPC cells. Strikingly, treatment with EVs secreted from highly metastatic NPC cells was significantly associated with rapid NPC progression and shorter survival in xenografted mice. These findings not only improve our understanding of EVs-mediated NPC metastatic mechanism but also have important implications for the detection and treatment of NPC patients accompanied by aberrant EGFR-rich EVs transmission.

Iron-Catalyzed Oxidative Coupling of Indoline-2-ones with Aminobenzamides via Dual C-H Functionalization.

We describe an unprecedented dual C-H functionalization of indolin-2-one via an oxidative C(sp3)-H/N-H/X-H (X = N, C, S) cross-coupling protocol, which is catalyzed by a simple iron salt under mild and ligand-free conditions and employs air (molecular oxygen) as the terminal oxidant. This method is readily applicable for the construction of tetrasubstituted carbon centers from methylenes and provides a wide variety of spiro N-heterocyclic oxindoles.

Tomato yellow leaf curl virus intergenic siRNAs target a host long noncoding RNA to modulate disease symptoms.

Tomato yellow leaf curl virus (TYLCV) and its related begomoviruses cause fast-spreading diseases in tomato worldwide. How this virus induces diseases remains largely unclear. Here we report a noncoding RNA-mediated model to elucidate the molecular mechanisms of TYLCV-tomato interaction and disease development. The circular ssDNA genome of TYLCV contains a noncoding intergenic region (IR), which is known to mediate viral DNA replication and transcription in host cells, but has not been reported to contribute directly to viral disease development. We demonstrate that the IR is transcribed in dual orientations during plant infection and confers abnormal phenotypes in tomato independently of protein-coding regions of the viral genome. We show that the IR sequence has a 25-nt segment that is almost perfectly complementary to a long noncoding RNA (lncRNA, designated as SlLNR1) in TYLCV-susceptible tomato cultivars but not in resistant cultivars which contains a 14-nt deletion in the 25-nt region. Consequently, we show that viral small-interfering RNAs (vsRNAs) derived from the 25-nt IR sequence induces silencing of SlLNR1 in susceptible tomato plants but not resistant plants, and this SlLNR1 downregulation is associated with stunted and curled leaf phenotypes reminiscent of TYLCV symptoms. These results suggest that the lncRNA interacts with the IR-derived vsRNAs to control disease development during TYLCV infection. Consistent with its possible function in virus disease development, over-expression of SlLNR1 in tomato reduces the accumulation of TYLCV. Furthermore, gene silencing of the SlLNR1 in the tomato plants induced TYLCV-like leaf phenotypes without viral infection. Our results uncover a previously unknown interaction between vsRNAs and host lncRNA, and provide a plausible model for TYLCV-induced diseases and host antiviral immunity, which would help to develop effective strategies for the control of this important viral pathogen.

Modeling of carrier transport in organic light emitting diode with random dopant effects by two-dimensional simulation.

To model the carrier transport in organic light-emitting diodes (OLEDs) with random dopant effects in the emitting layer, two-dimensional simulation was used. By including the Gaussian shape density of states and field-dependent mobility in the Poisson and drift-diffusion solver, the carrier transport, trapping in the dopant state, and radiative recombination were accurately modeled. To examine the model, the current-voltage characteristics of organic light-emitting devices were compared. The host material in the emitting layer was 2,2-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)biphenyl (BImBP), which was doped with bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) at various concentrations. By including the random doping model, the trend of mobility was altered and the radiative efficiency fitted experimental values well.

Migration of BTEX and Biodegradation in Shallow Underground Water through Fuel Leak Simulation.

To provide more reasonable references for remedying underground water, fuel leak was simulated by establishing an experimental model of a porous-aquifer sand tank with the same size as that of the actual tank and by monitoring the underground water. In the tank, traditional gasoline and ethyl alcohol gasoline were poured. This study was conducted to achieve better understanding of the migration and distribution of benzene, toluene, ethyl benzene, and xylene (BTEX), which are major pollutants in the underground water. Experimental results showed that, compared with conventional gasoline, the content peak of BTEX in the mixture of ethyl alcohol gasoline appeared later; BTEX migrated along the water flow direction horizontally and presented different pollution halos; BTEX also exhibited the highest content level at 45 cm depth; however, its content declined at the 30 and 15 cm depths vertically because of the vertical dispersion effect; the rise of underground water level increased the BTEX content, and the attenuation of BTEX content in underground water was related to the biodegradation in the sand tank, which mainly included biodegradation with oxygen, nitrate, and sulfate.