Pseudorabies virus VHS protein abrogates interferon responses by blocking NF-κB and IRF3 nuclear translocation.

Herpesviruses antagonize host antiviral responses through a myriad of molecular strategies culminating in the death of the host cells. Pseudorabies virus (PRV) is a significant veterinary pathogen in pigs, causing neurological sequalae that ultimately lead to the animal's demise. PRV is known to trigger apoptotic cell death during the late stages of infection. The virion host shutdown protein (VHS) encoded by UL41 plays a crucial role in the PRV infection process. In this study, we demonstrate that UL41 inhibits PRV-induced activation of inflammatory cytokine and negatively regulates the cGAS-STING-mediated antiviral activity by targeting IRF3, thereby inhibiting the translocation and phosphorylation of IRF3. Notably, mutating the conserved amino acid sites (E192, D194, and D195) in the RNase domain of UL41 or knocking down UL41 inhibits the immune evasion of PRV, suggesting that UL41 may play a crucial role in PRV's evasion of the host immune response during infection. These results enhance our understanding of how PRV structural proteins assist the virus in evading the host immune response.

Mammalian orthoreovirus capsid protein σ3 antagonizes RLR-mediated antiviral responses by degrading MAVS.

Mammalian orthoreovirus (MRV) outer capsid protein σ3 is a multifunctional protein containing a double-stranded RNA-binding domain, which facilitates viral entry and assembly. We reasoned that σ3 has an innate immune evasion function. Here, we show that σ3 protein localizes in the mitochondria and interacts with mitochondrial antiviral signaling protein (MAVS) to activate the intrinsic mitochondria-mediated apoptotic pathway. Consequently, σ3 protein promotes the degradation of MAVS through the intrinsic caspase-9/caspase-3 apoptotic pathway. Moreover, σ3 protein can also inhibit the expression of the components of the RNA-sensing retinoic acid-inducible gene (RIG)-like receptor (RLR) signaling pathway to block antiviral type I interferon responses. Mechanistically, σ3 inhibits RIG-I and melanoma differentiation-associated gene 5 expression is independent of its inhibitory effect on MAVS. Overall, we demonstrate that the MRV σ3 protein plays a vital role in negatively regulating the RLR signaling pathway to inhibit antiviral responses. This enables MRV to evade host defenses to facilitate its own replication providing a target for the development of effective antiviral drugs against MRV. IMPORTANCE: Mammalian orthoreovirus (MRV) is an important zoonotic pathogen, but the regulatory role of its viral proteins in retinoic acid-inducible gene-like receptor (RLR)-mediated antiviral responses is still poorly understood. Herein, we show that MRV σ3 protein co-localizes with mitochondrial antiviral signaling protein (MAVS) in the mitochondria and promotes the mitochondria-mediated intrinsic apoptotic pathway to cleave and consequently degrade MAVS. Furthermore, tryptophan at position 133 of σ3 protein plays a key role in the degradation of MAVS. Importantly, we show that MRV outer capsid protein σ3 is a key factor in antagonizing RLR-mediated antiviral responses, providing evidence to better unravel the infection and transmission mechanisms of MRV.

Pseudorabies virus UL38 attenuates the cGAS-STING signaling pathway by recruiting Tollip to promote STING for autophagy degradation.

Natural immunity is the first defense line of the host immune system, which plays a significant role in combating foreign pathogenic microorganisms. The IFN-ß (interferon-beta) signaling pathway, being a typical example of innate immunity, plays a vital function. This study aimed to elucidate the function of pseudorabies virus (PRV) UL38 protein (unique long region 38) in suppressing the activation of the IFN-ß signaling pathway. The findings from our study indicate that the PRV UL38 protein effectively hampers the activation of IFN-ß by poly (dA: dT) (poly(deoxyadenylic-deoxythymidylic)) and 2'3'-cGAMP (2'-3'-cyclic GMP-AMP). Furthermore, UL38 exhibits spatial co-localization with STING (stimulator of interferon genes) and effectively hinders STING dimerization. Subsequently, STING was downgraded to suppress the production of IFN-ß and ISGs (interferon stimulated genes). Immunoprecipitation analysis revealed that the interaction between UL38 and STING, which subsequently initiated the degradation of STING via selective autophagy mediated by TOLLIP (toll interacting protein). To summarize, this research elucidates the function of UL38 in counteracting the cGAS (cGAMP synthase)-STING-induced IFN-ß pathway. The PRV UL38 protein may attenuate the activation of IFN-ß as a means of regulating the virus's persistence in the host.

Wide Temperature Electrolytes for Lithium Batteries: Solvation Chemistry and Interfacial Reactions.

Improving the wide-temperature operation of rechargeable batteries is crucial for boosting the adoption of electric vehicles and further advancing their application scope in harsh environments like deep ocean and space probes. Herein, recent advances in electrolyte solvation chemistry are critically summarized, aiming to address the long-standing challenge of notable energy diminution at sub-zero temperatures and rapid capacity degradation at elevated temperatures (>45°C). This review provides an in-depth analysis of the fundamental mechanisms governing the Li-ion transport process, illustrating how these insights have been effectively harnessed to synergize with high-capacity, high-rate electrodes. Another critical part highlights the interplay between solvation chemistry and interfacial reactions, as well as the stability of the resultant interphases, particularly in batteries employing ultrahigh-nickel layered oxides as cathodes and high-capacity Li/Si materials as anodes. The detailed examination reveals how these factors are pivotal in mitigating the rapid capacity fade, thereby ensuring a long cycle life, superior rate capability, and consistent high-/low-temperature performance. In the latter part, a comprehensive summary of in situ/operational analysis is presented. This holistic approach, encompassing innovative electrolyte design, interphase regulation, and advanced characterization, offers a comprehensive roadmap for advancing battery technology in extreme environmental conditions.

A G-quadruplex/thioflavin T-based label-free biosensor to detect ClO- in stress-induced hypertension.

Hypochlorous acid (HClO), as an essential reactive oxygen species (ROS) in biological systems, plays a pivotal role in processes of physiology and pathology. Abnormal fluctuations in HClO concentration can lead to various diseases, such as inflammation, cardiovascular diseases, and neurodegeneration. Therefore, developing an approach to rapidly and sensitively quantify ClO- content is vital to biomedicine development and bioassays. Herein, we fabricated a novel "turn-on" label-free fluorescence DNA probe to specifically detect hypochlorite ion (ClO-) based on G-quadruplex formation. To this end, we designed a G-rich signal DNA sequence (S-DNA) and a block DNA sequence (B-DNA), followed by the introduction of ClO--responsive phosphorothioate (PS) into B-DNA. In the absence of ClO-, B-DNA hybridized with S-DNA, preventing G-quadruplex formation from S-DNA; this resulted in the relatively low fluorescence intensity of ThT. Once ClO- was added, the hydrolysis between PS and ClO- split the B-DNA into two fragments, resulting in B-DNA breaking away from S-DNA, allowing G-quadruplex formation from S-DNA and increasing the fluorescence intensity of ThT. Using this method, we can detect ClO- without the interference of additional reactive oxygen species. The detection limit of ClO- was as low as 10 nM. Furthermore, this method facilitates the detection of ClO- within the tissues of rats with stress-induced hypertension.

Mammalian reovirus µ1 protein attenuates RIG-I and MDA5-mediated signaling transduction by blocking IRF3 phosphorylation and nuclear translocation.

Mammalian reovirus (MRV) is a non-enveloped, gene segmented double-stranded RNA (dsRNA) virus. It is an important zoonotic pathogen that infects many mammals and vertebrates that act as natural hosts and causes respiratory and digestive tract diseases. Studies have reported that RIG-I and MDA5 in the innate immune cytoplasmic RNA-sensing RIG-like receptor (RLR) signaling pathway can recognize dsRNA from MRV and promote antiviral type I interferon (IFN) responses. However, the mechanism by which many MRV-encoded proteins evade the host innate immune response remains unclear. Here, we show that exogenous µ1 protein promoted the proliferation of MRV in vitro, while knockdown of MRV µ1 protein expression by shRNA could impair MRV proliferation. Specifically, µ1 protein inhibited MRV or poly(I:C)-induced IFN-ß expression, and attenuated RIG-I/MDA5-mediated signaling axis transduction during MRV infection. Importantly, we found that µ1 protein significantly decreased IFN-ß mRNA expression induced by MDA5, RIG-I, MAVS, TBK1, IRF3(5D), and degraded the protein expression of exogenous MDA5, RIG-I, MAVS, TBK1 and IRF3 via the proteasomal and lysosomal pathways. Additionally, we show that µ1 protein can physically interact with MDA5, RIG-I, MAVS, TBK1, and IRF3 and attenuate the RIG-I/MDA5-mediated signaling cascades by blocking the phosphorylation and nuclear translocation of IRF3. In conclusion, our findings reveal that MRV outer capsid protein µ1 is a key factor in antagonizing RLRs signaling cascades and provide new strategies for effective prevention and treatment of MRV infection.

Effects of the turbocharged Miller cycle strategy on the performance improvement and emission characteristics of diesel engines.

The turbocharged Miller cycle strategy is studied to improve the power density of diesel engines and reduce emissions. A thermodynamic model and a 1D simulation model of turbocharged diesel engine are established. Results show that the introduction of the Miller cycle reduces the thermal efficiency under naturally aspirated conditions because of the low effective compression ratio, whereas it increases the thermal efficiency under a turbocharged condition owing to the energy recovered by the turbocharger. Under restricted combustion pressure and fixed intake mass, the thermal efficiency first increases and then decreases with increasing Miller cycle ratio, and the peaks occur at approximately 30%-50%. The gain of isochoric combustion ratio overlaps the loss of effective compression ratio due to the Miller cycle on the lower side, whereas it reverses on the higher side. With maximum and equal intake mass, the maximum power initially increases and subsequently decreases with increasing Miller cycle ratio, reaching a peak at 40%. Under a fixed isochoric combustion ratio, the thermal efficiency first increases and then decreases with increasing intake mass, and the optimum intake mass corresponding to the highest thermal efficiency decreases with increasing Miller cycle ratio. The lower the restricted combustion pressure is, the higher the gain in power and thermal efficiency by the Miller cycle strategy. Based on the calculation of the 1D model validated using a practical engine, the power can be increased from 41.6 kW/L to 100 kW/L while the brake thermal efficiency can be increased from 34.98% into 38.55% by increasing the Miller cycle ratio from 19% to 30% and the combustion pressure from 17.7 MPa to 35 MPa. With the application of the supercharged Miller cycle, when the Miller cycle ratio is 30% and the power intensity is increased from 60 kW/L to 100 kW/L, NOx decreases by 32.4%, CO decreases by 28%, showing a tendency to decrease and then stabilize, and HC increases by 5.3%. When the power is 80 kW/L and the Miller cycle ratio is increased from 10% to 30%, NOx decreases by 8.6%, CO decreases by 2%, and HC increases by 0.04%.

Histone H1.2 Inhibited EMCV Replication through Enhancing MDA5-Mediated IFN-ß Signaling Pathway.

Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-ß and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation-inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.

Prognostic and immune infiltration features of disulfidptosis-related subtypes in breast cancer.

Breast cancer (BC) is a prominent cause of cancer incidence and mortality around the world. Disulfidptosis, a type of cell death, can induce tumor cell death. The purpose of this study was to analyze the potential impact of disulfidptosis-related genes (DRGs) on the prognosis and immune infiltration features of BC. Based on DRGs, we conducted an unsupervised clustering analysis on gene expression data of BC in TCGA-BRCA dataset and identified two BC subtypes, cluster1 and cluster2, with cluster1 showing a higher likelihood of favorable survival. Through immune analysis, we found that cluster1 had lower proportions of infiltration in immune-related cells, including aDCs, DCs, NK_cells, Th2_cells, and Treg. Based on the immunophenoscore (IPS) results, we inferred that cluster1 might benefit more from immune checkpoint inhibitors targeting CTLA-4 and PD1. Targeted small molecule prediction results showed that patients with cluster2 BC might respond better to antagonistic small molecule compounds, including clofazimine, lenalidomide, and epigallocatechin. Differentially expressed genes between the two subtypes were found to be enriched in signaling pathways related to steroid hormone biosynthesis, ovarian steroidogenesis, and neutrophil extracellular trap formation, according to enrichment analyses. In conclusion, this study identified BC subtypes based on DRGs so as to help predict patient prognosis and provide valuable tools for guiding clinical management and precise treatment of BC patients.

Targeting POLRMT by a first-in-class inhibitor IMT1 inhibits osteosarcoma cell growth in vitro and in vivo.

Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1's effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.

Prognostic value of oxygen inhalation therapy for simple nocturnal hypoxemia in COPD: a meta-analysis.

Objective: The effect of oxygen therapy on the prognosis of chronic obstructive pulmonary disease (COPD) with nocturnal hypoxemia (NOD) has been controversial. Therefore, this study systematically evaluated the relevant literature and included it into randomized controlled studies for meta-analysis to evaluate the efficacy and prognosis. Methods: We searched PubMed, EMBASE, web of science, Cochrane, China HowNet and Wanfang database for the literature on the prognosis of COPD patients with simple NOD from the establishment of the database to 30 June 2022. The outcome indicators were death and aggravation of the disease. The efficacy evaluation measures were pulmonary function and arterial blood gas results. The publication bias and heterogeneity of the included studies were evaluated. Results: A total of 621 patients from 5 studies were included in this meta-analysis, and there was no publication bias in the included studies. The total mortality of long-term oxygen therapy (LTOT) in COPD patients with simple NOD in oxygen therapy group (RR = 1.04; 95% CI: 0.81-1.33, p = 0.77), mortality (RR = 0.87; 95% CI: 0.58-1.31, p = 0.50), risk of progression to LTOT events (RR = 1.07; 95% CI: 0.76-1.51, p = 0.71). PaO2 in patients with COPD and simple NOD in oxygen therapy group was higher than that in non-oxygen therapy group (mean difference (MD) = 13.47; 95% CI: 3.49-23.46, p = 0.008), the decrease of PaCO2 level was not statistically significant (MD = -10.05; 95% CI: -26.36-6.27, p = 0.23). Conclusion: Oxygen therapy can improve the prognosis of blood oxygen partial pressure in COPD patients with simple NOD, but oxygen therapy has no significant effect on the survival rate, controlling the progression of the disease to LTOT and reducing the partial pressure of carbon dioxide.

Vinylene-Linked Emissive Covalent Organic Frameworks for White-Light-Emitting Diodes.

Covalent organic frameworks (COFs) have gained considerable attention due to their highly conjugated π-skeletons, rendering them promising candidates for the design of light-emitting materials. In this study, we present two vinylene-linked COFs, namely, VL-COF-1 and VL-COF-2, which were synthesized through the Knoevenagel condensation of 2,4,6-trimethyl-1,3,5-triazine with terephthalaldehyde or 4,4'-biphenyldicarboxaldehyde. Both VL-COF-1 and VL-COF-2 exhibited excellent chemical and thermal stability. The presence of vinylene linkages between the constituent building blocks in these COFs resulted in broad excitation and emission properties. Remarkably, the designed VL-COFs demonstrated bright emission, fast fluorescence decay, and high stability, making them highly attractive for optoelectronic applications. To assess the potential of these VL-COFs in practical devices, we fabricated white-light-emitting diodes (WLEDs) coated with VL-COF-1 and VL-COF-2. Notably, the WLEDs coated with VL-COF-1 achieved high-quality white light emission, closely approximating standard white light. The promising performance of VL-COF-coated WLEDs suggests the feasibility of utilizing COF materials for stable and efficient lighting applications.

Design of flavonol-loaded cationic gold nanoparticles with enhanced antioxidant and antibacterial activities and their interaction with proteins.

In this work, four structurally similar flavonols (galangin, kaempferol, quercetin and myricetin) were coated on the surface of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide (MUTAB)­gold nanoparticles (AuNPs) by two-step phase transfer and self-assembly, and the cationic MUTAB- AuNPs coated with flavonols (flavonol-MUTAB-AuNPs) were designed. Free radical scavenging and antibacterial experiments show that flavonol-MUTAB-AuNPs greatly improve the scavenging effect on DPPH, hydroxyl and superoxide anion radicals, and significantly enhance the inhibition effect on Staphylococcus aureus and Escherichia coli compared with flavonols and AuNPs. Then γ-globulin, fibrinogen, trypsin and pepsin were selected as representative proteins and their interaction with flavonol-MUTAB-AuNPs were investigated by various spectroscopic techniques. The fluorescence quenching mechanism of these four proteins by flavonol-MUTAB-AuNPs is static quenching. The binding constants Ka between them are in the range of 103 to 106. The interaction between them is endothermic, entropy-driven spontaneous process, and the main non-covalent force is the hydrophobic interaction. The effect of flavonol-MUTAB-AuNPs on the structure of the four proteins were investigated using UV-vis absorption spectra, synchronous fluorescence spectra and circular dichroism spectra. These results offer important insights into the essence of the interaction between flavonol-MUTAB-AuNPs and γ-globulin/fibrinogen/trypsin/pepsin. They will contribute to the development of safe and effective flavonol-MUTAB-AuNPs in biomedical fields.

Experimental studies on the particulate matter emission characteristics of a lateral swirl combustion system for direct injection diesel engines.

To analyze the particulate emission characteristics of a lateral swirl combustion system (LSCS), experimental research on a single-cylinder diesel engine was done and compared against the Turbocharger-Charge Air Cooling-Diesel Particle Filter Series combustion system (TCDCS) at different conditions. Compared to the TCDCS, the LSCS presents better combustion performance and lower total particle emission characteristics: As for the LSCS, the vast majority of the particle number size distributions shifted downward, indicating a decrease in the particle number concentration. The total particle number and mass concentrations of the LSCS decreased by 8.7-62.4% and 15.2-55.6% at various loads. The number concentration of particles smaller than approximately 8 nm increased for the LSCS, which can be attributed to the higher temperature and more thorough fuel/air mixture, facilitating the oxidation of large particles into small particles. Combined with the simulation, the LSCS perfectly exerts the wall-flow-guided effect, remarkably improving the fuel/air mixing quality and reducing the local over-concentration regions, which can inhibit the formation of particles. Hence, the LSCS effectively reduces the particle number and mass concentrations, exhibiting excellent particulate emission characteristics.

Mitigating Ion Migration with an Ultrathin Self-Assembled Ionic Insulating Layer Affords Efficient and Stable Wide-Bandgap Inverted Perovskite Solar Cells.

Wide-bandgap perovskite solar cells (PSCs) are attracting increasing attention because they play an irreplaceable role in tandem solar cells. Nevertheless, wide-bandgap PSCs suffer large open-circuit voltage (VOC ) loss and instability due to photoinduced halide segregation, significantly limiting their application. Herein, a bile salt (sodium glycochenodeoxycholate, GCDC, a natural product), is used to construct an ultrathin self-assembled ionic insulating layer firmly coating the perovskite film, which suppresses halide phase separation, reduces VOC loss, and improves device stability. As a result, 1.68 eV wide-bandgap devices with an inverted structure deliver a VOC of 1.20 V with an efficiency of 20.38%. The unencapsulated GCDC-treated devices are considerably more stable than the control devices, retaining 92% of their initial efficiency after 1392 h storage under ambient conditions and retaining 93% after heating at 65 °C for 1128 h in an N2 atmosphere. This strategy of mitigating ion migration via anchoring a nonconductive layer provides a simple approach to achieving efficient and stable wide-bandgap PSCs.

IFITM2 Presents Antiviral Response through Enhancing Type I IFN Signaling Pathway.

Interferon (IFN) helps cells fight viral infections by further inducing the expression of many downstream IFN-stimulated genes (ISGs). Human interferon-inducible transmembrane proteins (IFITM) are one of these ISGs. The antiviral function of human IFITM1, IFITM2, and IFITM3 are well known. In this study, we report that IFITM can significantly inhibit EMCV infectivity in HEK293 cells. Overexpression of IFITM proteins could promote IFN-ß production. Meanwhile, IFITMs facilitated type I IFN signaling pathway adaptor MDA5 expression. We detected the binding of IFITM2 to MDA5 in a co-immunoprecipitation assay. It was also found that the ability of IFITM2 to activate IFN-ß was significantly inhibited after interfering with MDA5 expression, suggesting that MDA5 may play an important role in the activation of the IFN-ß signaling pathway by IFITM2. Moreover, the N-terminal domain plays an active role in the antiviral activity and the activation of IFN-ß by IFITM2. These findings suggest that IFITM2 plays a vital role in antiviral signaling transduction. In addition, a positive feed-forward loop between IFITM2 and type I IFN establishes a key role for IFITM2 in enforcing innate immune responses.

Induced regulatory T cells modified by knocking down T-bet in combination with ectopic expression of inhibitory cytokines effectively protect graft-versus-host disease.

Induced regulatory T (iTreg) cells play a vital role in immune tolerance and in controlling chronic inflammation. Generated in the periphery, iTreg cells are suitable for responding to alloantigens and preventing transplant rejection. Nevertheless, their clinical application has been impeded by the plasticity and instability attributed to the loss of forkhead box protein 3 expression, raising concerns that iTreg may be converted to effector T cells and even exert a pathogenic effect. Herein, second-generation short hairpin RNAs loaded with 3 pairs of small interfering RNAs were utilized to target the T-box transcription factor TBX21. In addition, 2 immunosuppressive cytokines, namely, transforming growth factor beta and interleukin 10, were constitutively expressed. This novel engineering strategy allowed the generation of stably induced regulatory T (SI Treg) cells, which maintained the expression of forkhead box protein 3 even in an unfavorable environment and exerted potent immunosuppressive functions in vitro. Furthermore, SI Treg cells demonstrated an effector transcriptional profile. Finally, SI Treg cells showed a significant protective effect against graft-versus-host disease-related deaths in a xenotransplantation model. Collectively, these results signify that SI Treg cells hold great promise for future clinical application and offer a rational therapeutic approach for transplant rejection.

A bioinspired polydopamine-FeS nanocomposite with high antimicrobial efficiency via NIR-mediated Fenton reaction.

Ferrous and sulfur ions are essential elements for the human body, which play an active role in maintaining the body's normal physiology. Meanwhile, mussel-inspired polydopamine (PDA) possesses good hydrophilicity and biocompatibility. In the present work, ferrous sulfide embedded into polydopamine nanoparticles (PDA@FeS NPs) was designed and synthesized via a simple predoping polymerization-coprecipitation strategy and the intelligent PDA matrix successfully prevented the oxidation and agglomeration of FeS nanoparticles. Importantly, there was an obvious synergistic enhancement of the photothermal effect between polydopamine and ferrous sulfide. The PDA@FeS NPs exhibited excellent photothermal antibacterial effects against both E. coli and S. aureus. The near-infrared (NIR) light-mediated release of ferrous ions could reach about 26.5% under weakly acidic conditions, further triggering the Fenton reaction to produce toxic hydroxyl radicals (·OH) in the presence of hydrogen peroxide. The antibacterial mechanism could be attributed to cell membrane damage and cellular content leakage with the synergistic effect of PTT and CDT. This study highlighted the germicidal efficacy of PDA@FeS NPs and provided a new strategy for designing and developing next-generation antibacterial platforms.

Comparative study on the interaction between transferrin and flavonols: Experimental and computational modeling approaches.

Transferrin is the indispensable component in the body fluids and has been explored as a potential drug carrier for target drugs to cancer cells. Flavonols are widely distributed in plants and shown a wide range of biological activities. In the present study, the interaction between flavonols (including galangin, kaempferol, quercetin, and myricetin) and transferrin under physiological conditions was investigated by using experimental as well as computational approaches. Fluorescence data reveal that the fluorescence quenching mechanism of transferrin by flavonols is static quenching. Transferrin has moderate affinity with flavonols, and the binding constants (Ka) are 103-104 L/mol. In addition, there are two different binding sites for the interaction between kaempferol and transferrin. Thermodynamic parameter analysis shows that the interaction of flavonols and transferrin is synergistically driven by enthalpy and entropy. Hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that flavonols decrease the hydrophobicity of the microenvironment around tryptophan (Trp) and have no effect on the microenvironment around tyrosine (Tyr). UV-vis and CD spectra show that the interaction between transferrin and flavonols leads to the loosening and unfolding of transferrin backbone. The increase of ß-sheet is accompanied by the decrease of α-helix and ß-turn. The specific binding sites of flavonols to transferrin are confirmed by molecular docking. Molecular dynamic simulation suggests that the transferrin-flavonols docked complex is stable throughout the simulation trajectory.

Relationships of leisure activities with physical and cognitive functions among Chinese older adults: A prospective community-based cohort study.

OBJECTIVES: Based on a prospective design, this study aimed to investigate the relationships of leisure activities with physical and cognitive functions among Chinese older adults. METHODS: The respondents aged 65 years or more were selected from the 2014-2018 of the Chinese Longitudinal Healthy Longevity Survey. Physical function measurement indicators were reflected by activities of daily living (ADL), instrumental activities of daily living (IADL), and physical performance (PP), while cognitive function was assessed by Mini-Mental State Examination. Fine-Gray competing risk regression models were used to analyze the data. RESULTS: Using the figures for 2014 as a baseline for the study, we included 6047, 6216, 5951, and 5916 respondents in the ADL, IADL, PP, and cognitive function analyses, respectively. The prospective results showed that keeping domestic animals or pets was related to a lower risk of ADL disability of respondents after adjustment (SHR: 0.619, 95% CI: 0.486, 0.788). Similarly, taking part in social activities (SHR: 0.781, 95%CI: 0.658, 0.929) and reading books or newspapers (SHR: 0.793, 95% CI: 0.656, 0.958) were associated with a lower risk of IADL disability. Playing cards or mahjong was correlated with a lower risk of cognitive impairment (SHR: 0.669, 95% CI: 0.507, 0.882), while keeping domestic animals or pets was related to a higher risk of cognitive impairment (SHR: 1.279, 95% CI: 1.047, 1.562). CONCLUSION: Participation in leisure activities moderately may decrease the risk of a decline in physical and cognitive functions among Chinese older adults.