Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165.

BACKGROUND: Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. OBJECTIVES: We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. METHODS: We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. RESULTS: HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. CONCLUSION: These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

Promising Intestinal Microbiota Associated with Clinical Characteristics of COPD Through Integrated Bioinformatics Analysis.

Introduction: Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD. Methods: The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research. Results: No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen. Conclusion: The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.

Impact of Chiral Spinterfaces on Magneto-Photoluminescence Effects for Chiral Lead Halide Perovskites.

Chiral lead halide perovskites (LHPs) have been widely investigated in chiroptical spintronics due to their significant Rashba spin-orbit coupling (SOC) and chiral-induced spin selectivity (CISS). Ferromagnet/LHP spinterface stems from the orbital hybridization at the interface of the ferromagnet and the nonmagnetic semiconductor, where interfacial density of state is spin-dependent. By far, the impact of the ferromagnet/chiral LHP spinterface on magneto-photoluminescence (Magneto-PL) of chiral LHPs remains unknown. In this work, we find that the negative and tunable Magneto-PL effects for the pristine LHP bulk film can be drastically enhanced by incorporating ferromagnetic/chiral LHP interfaces. A large Magneto-PL magnitude can reach approximately -13% for the Ni/(S-MBA)2PbI4 interface at the field strengths of ±900 mT. With the assistance of circularly polarized PL spectra, anisotropic magneto-resistance, and X-ray photoelectron spectroscopy measurements, we demonstrate that the ferromagnet/chiral LHP interfaces are chirality/spin-dependent and possess ferromagnetic property due to distinct magnetic switching behavior and electronic orbit coupling at interfaces, which boost the Rashba splitting and spin mixing. The comprehensive effects of Rashba-induced exciton states and chiral-induced SOC at chiral spinterfaces with CISS are responsible for the enhanced Magneto-PL of Ni/(R/S-MBA)2PbI4. It is postulated that the chiral spinterfaces play a dominant role for achieving large and tunable magneto-optical effect of chiral LHPs. This work paves the way for chiroptical spintronic applications.

Spin-photogalvanic effect in chiral lead halide perovskites.

Low-temperature solution-made chiral lead halide perovskites (LHPs) have spontaneous Bychkov-Rashba spin orbit coupling (SOC) and chiral-induced spin selectivity (CISS) qualities. Their coexistence may give rise to considerable spin and charge conversion capabilities for spin-orbitronic applications. In this study, we demonstrate the spin-photogalvanic effect for (R-MBA)2PbI4 and (S-MBA)2PbI4 polycrystalline film-based lateral devices (100 µm channel length). The light helicity dependence of the short-circuit photocurrent exhibits the circular photogalvanic effect (CPGE) and linear photogalvanic effect (LPGE) with decent two-fold symmetry for a complete cycle in a wide temperature range from 4 K to 300 K. Because of the Rashba SOC and the material helicity, the effect is converse for the two chiral LHPs. In addition, its magnitude and sign can be effectively tuned by constant magnetic fields. The Rashba effect, CISS-generated unbalanced spin transport, and chiral-induced magnetization are mutually responsible for it. Our study evidently proves the future prospect of using chiral LHPs for spin-orbitronics.

The Burden of COPD in China and Its Provinces: Findings From the Global Burden of Disease Study 2019.

In China, chronic obstructive pulmonary disease (COPD) was accounted for a quarter of the global COPD population and has become a large economic burden. However, the comprehensive picture of the COPD burden, which could inform health policy, is not readily available for all of the provinces of China. Here, we aimed to describe the burden of COPD in China, providing an up-to-date and comprehensive analysis at the national and provincial levels, and time trends from 1990 to 2019. Following the methodology framework and general analytical strategies used in the GBD 2019, we analyzed the incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years with life lost (YLLs) attributable to COPD across China and the corresponding time trends from 1990 to 2019, stratified by age and province. In order to quantify the secular trends of the burden of COPD, the estimated annual percentage changes were calculated by the linear regression model of age-standardized rates (ASRs) and calendar years. We also presented the contribution of risk factors to COPD-related mortality and DALYs. The association between COPD burden and socio-demographic index (SDI) were also evaluated. From 1990 to 2019, the incidence and prevalence numbers of COPD increased by 61.2 and 67.8%, respectively, whereas the number of deaths and DALYs owing to COPD decreased. The ASRs of COPD burden, including incidence, prevalence, mortality, DALYs, YLDs, and YLLs continuously decreased from 1990 to 2019. The crude rates of COPD burden dramatically increased with age and reached a peak in the older than 95 years age group. In 2019, the leading risk factor for COPD mortality and DALYs was tobacco use in the whole population, but ambient particulate matter pollution was the most significant risk factor in females. At the provincial level, the ASRs of COPD burden was significantly associated with the SDIs, with the highest ASRs in the western provinces with low SDIs. Collectively, our study indicated that COPD remains an important public health problem in China. Geographically targeted considerations should be developed to enhance COPD health and reduce the COPD burden throughout China and in specific provinces.

An unprecedented spike of the electroluminescence turn-on transience from guest-doped OLEDs with strong electron-donating abilities of host carbazole groups.

An unreported unprecedented spike of ∼µs line-width, followed by an overshoot, was discovered at the rising edge of transient electroluminescence (TEL) from guest-doped organic light-emitting diodes with strong electron-donating abilities from the host carbazole groups. By changing the device structures and TEL measurement parameters, a series of experimental results demonstrate that this TEL spike is not related to exciton interactions such as singlet-triplet and triplet-triplet annihilations but originated from the radiative recombination of pre-stored electrons with injected holes. Surprisingly, these pre-stored guest electrons do not come from the energy-level traps in the host-guest systems; instead, the guest molecules receive the electrons transferred from the host carbazole groups due to their strong electron-donating abilities. Moreover, the observed spikes show rich and extraordinary temperature dependences. Based on the detailed understanding of the spike formation mechanism, we have proposed the requirements for the occurrence of spike and realized the artificial adjustments of the spike intensity. For instance, the instantaneous luminescent intensity of this spike can reach over 80 times the magnitude of the TEL plateau. Accordingly, this work deepens the physical understanding of this novel spike in TEL and paves the way for fabricating an electro-optic sensor to detect instantaneous weak current signals.

Achievement of High-Level Reverse Intersystem Crossing in Rubrene-Doped Organic Light-Emitting Diodes.

Using the fingerprint magneto-electroluminescence trace, we observe a fascinating high-level reverse intersystem crossing (HL-RISC) in rubrene-doped organic light-emitting diodes (OLEDs). This HL-RISC is achieved from high-lying triplet states (T2,rub) transferred from host triplet states by the Dexter energy transfer to the lowest singlet states (S1,rub) in rubrene. Although HL-RISC decreases with bias current, it increases with lowering temperature. This is contrary to the temperature-dependent RISC from conventional thermally activated delayed fluorescence, because HL-RISC is an exothermic process instead. Moreover, owing to the competition of exciton energy transfer with direct charge trap, HL-RISC changes nonmonotonically with the dopant concentration and increases luminous efficiency to a maximum at 10% of rubrene, which is about ten times greater than that from the pure-rubrene device. Additionally, the HL-RISC process is not observed in bare rubrene-doped films because of the absence of T2,rub. Our findings pave the way for designing highly efficient orange fluorescent OLEDs.

Spin-pair state-induced exceptional magnetic field responses from a thermally activated delayed fluorescence-assisted fluorescent material doping system.

The thermally activated delayed fluorescence (TADF) material 2,3,5,6-tetrakis(3,6-diphenylcarbazol-9-yl)-1,4-dicyanobenzene (4CzTPN-Ph) and the conventional fluorescent dopant 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) were used to co-dope the host material 4,4'-bis(carbazol-9-yl)biphenyl (CBP) for the fabrication of TADF-assisted fluorescent organic light-emitting diodes (OLEDs). Some exceptional magnetic field effect (MFE) curves with abundant structures and four tunable components within a low magnetic field range (≤50 mT) were obtained, in sharp contrast to the maximum of two components observed in typical OLEDs. These MFE components were easily tuned by the injection current, dopant concentration, working temperature, and dopant energy gap, leading to a wide variety of MFE curve line shapes. The experimental results are attributed to the spin-pair state inter-conversions occurring in the device, including intersystem crossing (ISC) of CBP polaron pairs, ISC of 4CzTPN-Ph polaron pairs, reverse ISC (RISC) of 4CzTPN-Ph excitons, RISC of DCJTB polaron pairs, DCJTB triplet fusion, and DCJTB triplet-charge annihilation. Moreover, the exciton energy transfer processes among the host material and the guest dopants had a pronounced impact on the formation of these four components. This work gives a deeper understanding of the microscopic mechanisms of TADF-based co-doped systems for the further development of organic magnetic field effects in the extensive field of OLEDs.

Using magneto-electroluminescence as a fingerprint to identify the spin polarization and spin-orbit coupling of magnetic nanoparticle doped polymer light emitting diodes.

The spin polarization and spin-orbit coupling (SOC) in polymer light emitting diodes (PLEDs) with the active layer doped with Fe3O4 nanoparticles (NPs) were identified through magneto-electroluminescence (MEL). By comparing the MEL characteristics such as linewidth and magnitude between PLEDs with and without Fe3O4 dopant, we confirmed the existence of spin polarization, but ruled out the existence of SOC. Although the spin polarization is positive to electroluminescence, the brightness-current characteristics suggested that the current efficiency of the doped PLED does not improve. We attributed it to the current leakage caused by the Fe3O4 NPs in the active layer. This work is beneficial for us to further understand the effect of magnetic nanoparticle doping on the dynamic behavior of excitons and polaron pairs in organic semiconductor devices.

Intersystem Crossing and Triplet Fusion in Singlet-Fission-Dominated Rubrene-Based OLEDs Under High Bias Current.

Singlet fission is usually the only reaction channel for excited states in rubrene-based organic light-emitting diodes (OLEDs) at ambient temperature. Intriguingly, we discover that triplet fusion (TF) and intersystem crossing (ISC) within rubrene-based devices begin at moderate and high current densities (j), respectively. Both processes enhance with decreasing temperature. This behavior is discovered by analyzing the magneto-electroluminescence curves of the devices. The j-dependent magneto-conductance, measured at ambient temperature indicates that spin mixing within polaron pairs that are generated by triplet-charge annihilation (TQA) causes the occurrence of ISC, while the high concentrations of triplets are responsible for generating TF. Additionally, the reduction in exciton formation and the elevated TQA with decreasing temperature may contribute to the enhanced ISC at low temperatures. This work provides considerable insight into the different mechanisms that occur when a high density of excited states exist in rubrene and reasonable reasons for the absence of EL efficiency roll-off in rubrene-based OLEDs.