Plasma Induced Atomic-Scale Soldering Enhanced Efficiency and Stability of Electrocatalysts for Ampere-Level Current Density Water Splitting.

Industrial water electrolysis typically operates at high current densities, the efficiency and stability of catalysts are greatly influenced by mass transport processes and adhesion with substrates. The core scientific issues revolve around reducing transport overpotential losses and enhancing catalyst-substrate binding to ensure long-term performance. Herein, vertical Ni-Co-P is synthesized and employed plasma treatment for dual modification of its surface and interface with the substrate. The (N)Ni-Co-P/Ni3N cathode exhibits an ultra-low overpotential of 421 mV at 4000 mA cm-2, and the non-noble metal system only requires a voltage of 1.85 V to reach 1000 mA cm-2. When integrated into an anion exchange membrane (AEM) electrolyzer, it can operate stably for >300 h at 500 mA cm-2. Under natural light, the solar-driven AEM electrolyzer operates at a current density up to 1585 mA cm-2 with a solar-to-hydrogen efficiency (SHT) of 9.08%. Density functional theory (DFT) calculations reveal that plasma modification leads to an "atomic-scale soldering" effect, where the Ni3N strong coupling with the Co increases free charge density, simultaneously enhancing stability and conductivity. This research offers a promising avenue for optimizing ampere-level current density water splitting, paving the way for efficient and sustainable industrial hydrogen production.

Duck circovirus regulates the expression of duck CLDN2 protein by activating the MAPK-ERK pathway to affect its adhesion and infection.

Duck circovirus (DuCV) is widely recognized as a prominent virus in China's duck farming industry, known for its ability to cause persistent infections and significant immunosuppression, which can lead to an increased susceptibility to secondary infections, posing a significant threat to the duck industry. Moreover, clinical evidence also indicates the potential vertical transmission of the virus through duck embryos to subsequent generations of ducklings. However, the limited availability of suitable cell lines for in vitro cultivation of DuCV has hindered further investigation into the molecular mechanisms underlying its infection and pathogenicity. In this study, we observed that oral DuCV infection in female breeding ducks can lead to oviduct, ovarian, and follicular infections. Subsequently, the infection can be transmitted to the fertilized eggs, resulting in the emergence of virus-carrying ducklings upon hatching. In contrast, the reproductive organs of male breeding ducks were unaffected by the virus, thus confirming that vertical transmission of DuCV primarily occurs through infection in female breeding ducks. By analyzing transcriptome sequencing data from the oviduct, we focused on claudin-2, a gene encoding the tight junction protein CLDN2 located on the cell membrane, which showed significantly increased expression in DuCV-infected oviducts of female breeding ducks. Notably, CLDN2 was confirmed to interact with the unique structural protein of DuCV, namely capsid protein (Cap), through a series of experimental approaches including co-immunoprecipitation (co-IP), GST pull-down, immunofluorescence, and adhesion-blocking assays. Furthermore, we demonstrated that the Cap protein binds to the extracellular loop structural domains EL1 and EL2 of CLDN2. Subsequently, by constructing a series of truncated bodies of the CLDN2 promoter region, we identified the transcription factor SP5 for CLDN2. Moreover, we found that DuCV infection triggers the activation of the MAPK-ERK signaling pathway in DEF cells and ducks, leading to an upregulation of SP5 and CLDN2 expression. This process ultimately leads to the transportation of mature CLDN2 to the cell surface, thereby facilitating increased virus adherence to the target organs. In conclusion, we discovered that DuCV utilizes host CLDN2 proteins to enhance adhesion and infection in oviducts and other target organs. Furthermore, we elucidated the signaling pathways involved in the interaction between DuCV Cap proteins and CLDN2, which provides valuable insights into the molecular mechanism underlying DuCV's infection and vertical transmission. IMPORTANCE: Although duck circovirus (DuCV) poses a widespread infection and a serious hazard to the duck industry, the molecular mechanisms underlying DuCV infection and transmission remain elusive. We initially demonstrated vertical transmission of DuCV through female breeding ducks by simulating natural infection. Furthermore, a differentially expressed membrane protein CLDN2 was identified on the DuCV-infected oviduct of female ducks, and its extracellular loop structural domains EL1 and EL2 were identified as the interaction sites of DuCV Cap proteins. Moreover, the binding of DuCV Cap to CLDN2 triggered the intracellular MAPK-ERK pathway and activated the downstream transcription factor SP5. Importantly, we demonstrated that intracellular Cap also interacts with SP5, leading to upregulation of CLDN2 transcription and facilitating enhanced adherence of DuCV to target tissue, thereby promoting viral infection and transmission. Our study sheds light on the molecular mechanisms underlying vertical transmission of DuCV, highlighting CLDN2 as a promising target for drug development against DuCV infection.

Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.

Introduction: Ionizing radiation has been widely used in industry, medicine, military and agriculture. Radiation-induced skin injury is a significant concern in the context of radiotherapy and accidental exposure to radiation. The molecular changes at the single-cell level and intercellular communications during radiation-induced skin injury are not well understood. Methods: This study aims to illustrate this information in a murine model and human skin samples from a radiation accident using single-cell RNA sequencing (scRNA-Seq). We further characterize the functional significance of key molecule, which may provide a potential therapeutic target. ScRNA-Seq was performed on skin samples from a nuclear accident patient and rats exposed to ionizing radiation. Bioinformatic tools were used to analyze the cellular heterogeneity and preferential mRNAs. Comparative analysis was performed to identify dysregulated pathways, regulators, and ligand-receptor interactions in fibroblasts. The function of key molecule was validated in skin cells and in three mouse models of radiation-induced skin injury. Results: 11 clusters in human skin and 13 clusters of cells in rat skin were depicted respectively. Exposure to ionizing radiation caused changes in the cellular population (upregulation of fibroblasts and endothelial cells, downregulation of keratinocytes). Fibroblasts and keratinocytes possessed the most interaction pairs with other cell lineages. Among the five DEGs common to human and rat skins, Nur77 was highly expressed in fibroblasts, which mediated radiosensitivity by cell apoptosis and modulated crosstalk between macrophages, keratinocytes and endothelial cells in radiation-induced skin injury. In animal models, Nur77 knock-out mice (Nur77 -/-) showed more severe injury after radiation exposure than wild-type counterparts in three models of radiation-induced skin injury with complex mechanisms. Conclusion: The study reveals a single-cell transcriptional framework during radiation-induced skin injury, which provides a useful resource to uncover key events in its progression. Nur77 is a novel target in radiation-induced skin injury, which provides a potential therapeutic strategy against this disease.

Stratified analysis of the association between anti-obesity medications and digestive adverse events: a real-world study based on the FDA adverse event reporting system database.

BACKGROUND: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs. METHODS: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis. RESULTS: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42-3.6). Orlistat (ROR = 3.30, 95% CI: 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45-10.88) with phentermine-topiramate still needs further clarification. CONCLUSIONS: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.

Analysis of canopy interception characteristics and influencing factors in typical artificial forest in the Loess Plateau semi-arid region.

Interception loss (IL) is an important process in the hydrological cycle within semi-arid forest ecosystems, directly affecting the amount of effective rainfall. However, the factors influencing IL during individual rainfall events remain to be quantified. This study collected rainfall, vegetation, and interception data during the 2022 and 2023 growing seasons in a typical black locust forest within the Zhifanggou watershed. It employed the Random Forest Regression (RFR) and back-propagation neural network (BPNN) methods to quantitatively evaluate the contribution rates of various factors to the IL and interception loss percentage (ILP). The IL among the 48 effective rainfall events was 172.05 mm, accounting for 19.54% of the rainfall amount. IL and ILP increased as the distance from the trunk decreased. During all rainfall events, both IL and ILP were significantly negatively correlated with the leaf area index (LAI) and canopy cover (CC); IL is significantly positively correlated with total rainfall (TR) and rainfall intensity (RI), while ILP is significantly negatively correlated with TR, RI, and rainfall duration (RD). The BPNN and RFR results indicated that rainfall, canopy, and tree characteristics contributed 43.06%, 44.79%, and 12.15% to IL, respectively, and 57.27%, 34.09%, and 8.63% to ILP, respectively. TR, CC, and LAI represented the primary influencing factors. Rainfall and canopy characteristics were the main factors affecting IL (ILP). As rainfall event magnitude increases, canopy contributions to IL and ILP decrease. In semi-arid areas, managing forest canopies to control IL helps address water imbalances in ecosystems.

The value of the systemic immune-inflammation index in assessing disease severity in autoimmune encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE. METHODS: Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity. RESULTS: This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis. CONCLUSIONS: Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course.

In situ self-assembly of pulp microfibers and nanofibers into a transparent, high-performance and degradable film.

Despite the significant properties of fossil plastics, the current unsustainable methods employed in production, usage and disposal present a grave threat to both energy and environment. The development of degradable biomass materials as substitutes for fossil plastics can effectively address the energy-environment paradox at the source. Here, we prepared novel micro-nano multiscale composite films through assembling and crosslinking nanocellulose with coniferous wood pulp microfibers. The composite film combines the advantages of microfibers and nanocellulose, achieving a maximum transmittance of 91 %, foldability, excellent mechanical properties (tensile strength: 51.3 MPa, elongation at break: 4 %, young's modulus: 3.4 GPa), high thermal stability and complete degradation within 40 days. The composite film exhibits mechanochemical self-healing and retains properties even after fracture. Such exceptional performance fully meets the requirements for substituting petroleum plastics. By incorporating CaAlSiN3:Eu2+ into the composite film, it enables dual emission of red and blue light, thereby being able to promote plant growth and presenting potential as a novel sustainable alternative for agricultural films. By assembling microfiber and nanocellulose, such novel strategy is presented for the fabrication of high-quality biomass materials, thereby offering a promising avenue towards environment-friendly resource-sustainable new materials.

Building running-friendly cities: effects of streetscapes on running using 9.73 million fitness tracker data in Shanghai, China.

The association between built environment and physical activity has been recognized. However, how and to what extent microscale streetscapes are related to running activity remains underexplored, partly due to the lack of running data in large urban areas. Moreover, few studies have examined the interactive effects of macroscale built environment and microscale streetscapes. This study examines the main and interactive effects of the two-level environments on running intensity, using 9.73 million fitness tracker data from Keep in Shanghai, China. Results of spatial error model showed that: 1) the explanatory power of microscale streetscapes was higher than that of macroscale built environment with R2 of 0.245 and 0.240, respectively, which is different from the prior finding that R2 is greater for macroscale built environment than for microscale streetscape; 2) sky and green view indexes were positively associated with running intensity, whereas visual crowdedness had a negative effect; 3) there were negative interactions of land use Herfindahl-Hirschman index with sky and green view indexes, while a positive interaction was observed for visual crowdedness. To conclude, greener, more open and less visually crowded streetscapes, can promote running behavior and enhance the benefits of land use mix as well. The findings highlight the importance of streetscapes in promoting running behavior, instead of a supplement to macroscale built environment.

Introduction of polymeric ionic liquids containing quaternary ammonium groups to construct high-temperature proton exchange membranes with high proton conductivity and stability.

A series of membrane materials suitable for high-temperature proton exchange membranes (HT-PEM) were successfully prepared by introducing polymeric ionic liquids (PILs) containing quaternary ammonium groups into ether-bonded polybenzimidazole (OPBI). The structure of the cross-linked membrane has a strong interaction with phosphoric acid (PA), which enhances proton transport and PA retention. To ensure better overall performance of the cross-linked membrane, the optimal PIL content is 30 wt% (OPBI-PIL-30 %). The PA uptake of OPBI-PIL-30 % membrane was 323.24 %, and the proton conductivity at 180 â„ƒ was 113.94 mS cm-1, which was much higher than that of OPBI membrane. It is noteworthy that the PA retention of OPBI-PIL-30 % membrane could reach 71.38 % after 240 h of testing under the harsh environment of 80 â„ƒ/40 % RH. The membrane showed better acid retention capacity of 86.89 % at 160 â„ƒ under anhydrous environment. The OPBI-PIL-20 % membrane achieved the maximum power density of 436.19 mW cm-2, attributed to its favorable mechanical characteristics and proton conductivity. By these excellent properties, it is shown that OPBI-PIL-X membranes containing quaternary ammonium groups have the potential to be applied in high temperature proton exchange membrane fuel cells (HT-PEMFCs).

The photosynthetic performance and photoprotective role of carotenoids response to light stress in intertidal red algae Neoporphyra haitanensis.

Neoporphyra haitanensis, a red alga harvested for food, thrives in the intertidal zone amid dynamic and harsh environments. High irradiance represents a major stressor in this habitat, posing a threat to the alga's photosynthetic apparatus. Interestingly, N. haitanensis has adapted to excessive light despite the absence of a crucial xanthophyll cycle-dependent photoprotection pathway. Thus, it is valuable to investigate the mechanisms by which N. haitanensis copes with excessive light and to understand the photoprotective roles of carotenoids. Under high light intensities and prolonged irradiation time, N. haitanensis displayed reduction in photosynthetic efficiency and phycobiliproteins levels, as well as different responses in carotenoids. The decreased carotene contents suggested their involvement in the synthesis of xanthophylls, as evidenced by the up-regulation of lycopene-ß-cyclase (lcyb) and zeaxanthin epoxidase (zep) genes. Downstream xanthophylls such as lutein, zeaxanthin, and antheraxanthin increased proportionally to light stress, potentially participating in scavenging reactive oxygen species (ROS). When accompanied by the enhanced activity of ascorbate peroxidase (APX), these factors resulted in a reduction in ROS production. The responses of intermediates α-cryptoxanthin and ß-cryptoxanthin were felt somewhere between carotenes and zeaxanthin/lutein. Furthermore, these changes were ameliorated when the organism was placed in darkness. In summary, down-regulation of the organism's photosynthetic capacity, coupled with heightened xanthophylls and APX activity, activates photoinhibition quenching (qI) and antioxidant activity, helping N. haitanensis to protect the organism from the damaging effects of excessive light exposure. These findings provide insights into how red algae adapt to intertidal lifestyles.

Thermally Stable and Transparent Polyimide Derived from Side-Group-Regulated Spirobifluorene Unit for Substrate Application.

Advancements in flexible electronic technology, especially the progress in foldable displays and under-display cameras (UDC), have created an urgent demand for high-performance colorless polyimide (CPI). However, current CPIs lack sufficient heat resistance for substrate applications. In this work, four kinds of rigid spirobifluorene diamines are designed, and the corresponding polyimides are prepared by their condensation with 5,5'-(perfluoropropane-2,2-diyl) bis(isobenzofuran-1,3-dione) (6FDA) or 9,9-bis(3,4-dicarboxyphenyl) fluorene dianhydride (BPAF). The rigid and conjugated spirobifluorene units endow the polyimides with higher glass transition temperature (Tg) ranging from 356 to 468 °C. Their optical properties are regulated by small side groups and spirobifluorene structure with a periodically twisted molecular conformation. Consequently, a series of CPIs with an average transmittance ranging from 75% to 88% and a yellowness index (YI) as low as 2.48 are obtained. Among these, 27SPFTFA-BPAF presents excellent comprehensive performance, with a Tg of 422 °C, a 5 wt.% loss temperature (Td5) of 562 °C, a YI of 3.53, and a tensile strength (δmax) of 140 MPa, respectively. The mechanism underlying the structure-property relationship is investigated by experimental comparison and theoretical calculation, and the proposed method provides a pathway for designing highly rigid conjugated CPIs with excellent thermal stability and transparency for photoelectric engineering.

Asymmetric Intramolecular Amination Catalyzed with Cp*Ir-SPDO via Nitrene Transfer for Synthesis of Spiro-Quaternary Indolinone.

An asymmetric intramolecular spiro-amination to high steric hindering α-C-H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H-F bonds between [SbF6]- and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

Perceived built environment as a mediator linking objective built environment and leisure-time physical activity in Chinese cities.

Numerous studies have suggested that the perceived built environment is shaped by the objective built environment and influences human physical activity. However, the empirical examination of this pathway remains scant. Addressing this gap, our study investigates whether the built environment affects leisure-time physical activity through its impact on the perceived built environment, utilizing data collected from 760 residents in Fuzhou, China. Structural Equation Modeling results reveal a modest correlation between objective and perceived built environment elements, with the objective built environment being a stronger predictor of leisure-time physical activity. Notably, perceived recreational facilities significantly mediate the relationship between objective recreational facilities and leisure-time physical activity, accounting for 15% of the variance in physical activity due to objective recreational facilities. This mediation effect is consistent across subpopulations, irrespective of residential self-selection biases. These results highlight the imperative for urban planning and policy to extend beyond mere spatial allocation of amenities to enhancing both the actual and perceived accessibility of these facilities, thus underlining the study's profound implications for public health and urban development strategies.

Can good neighbourhood perception magnify the positive effect of favourable built environment on recreational walking in China?

BACKGROUND: It remains unknown whether good neighbourhood perception can enhance the benefits of favourable built environment to physical activity. Moreover, the moderation pattern is less understood in developing countries. OBJECTIVES: This work aims to examine the moderation effects of perceived neighbourhood safety and aesthetics on the relationship between built environment and time for recreational walking. METHODS: We performed the examination using a sample of 760 residents in Fuzhou City, China. The Negative Binomial Regression Model was developed to examine the moderation roles of neighbourhood safety and aesthetics on the impact of built environment, adjusting for the effects of location, socioeconomic, personal preferences and social environment factors. Moreover, two sensitivity analyses were performed to test whether the moderators found are robust to the control of residential self-selection, and differential measures of conceptually-comparable aspects of built environment. RESULTS: We found stronger associations of time for recreational walking with road density and proportion of parks and squares POIs for residents with high perception of neighbourhood safety, compared to those with low perception of neighbourhood safety. There was a greater effect of the proportion of parks and squares POIs, when perceived aesthetics was high than when perceived aesthetics was low. The findings of neighbourhood safety and aesthetics as moderator, were robust in the two sensitivity analyses. No significant moderation effect was found for land use diversity. CONCLUSIONS: High perceived neighbourhood safety can magnify the positive effects of road connectivity and accessibility to parks and squares. Neighbourhood aesthetics positively moderates the association of time for recreational walking with accessibility to parks and squares. The findings emphasize the need to consider safety- and aesthetics-specific differences in estimates of built environment effects. Improvements in neighbourhood safety and aesthetics are key to effective interventions in built environment to better promote physical activity.

Moderation Effects of Streetscape Perceptions on the Associations Between Accessibility, Land Use Mix, and Bike-Sharing Use: Cross-Sectional Study.

Background: Cycling is known to be beneficial for human health. Studies have suggested significant associations of physical activity with macroscale built environments and streetscapes. However, whether good streetscapes can amplify the benefits of a favorable built environment on physical activity remains unknown. Objective: This study examines whether streetscape perceptions can modify the associations between accessibility, land use mix, and bike-sharing use. Methods: This cross-sectional study used data from 18,019,266 bike-sharing orders during weekends in Shanghai, China. A 500 × 500 m grid was selected as the analysis unit to allocate data. Bike-sharing use was defined as the number of bike-sharing origins. Street view images and a human-machine adversarial scoring framework were combined to evaluate lively, safety, and wealthy perceptions. Negative binomial regression was developed to examine the independent effects of the three perceptual factors in both the univariate model and fully adjusted model, controlling for population density, average building height, distance to nearest transit, number of bus stations, number of points of interest, distance to the nearest park, and distance to the central business district. The moderation effect was then investigated through the interaction term between streetscape perception and accessibility and land use mix, based on the fully adjusted model. We also tested whether the findings of streetscape moderation effects are robust when examinations are performed at different geographic scales, using a small-sample statistics approach and different operationalizations of land use mix and accessibility. Results: High levels of lively, safety, and wealthy perceptions were correlated with more bike-sharing activities. There were negative effects for the interactions between the land use Herfindahl-Hirschman index with the lively perception (ß=-0.63; P=.01) and safety perception (ß=-0.52; P=.001). The interaction between the lively perception and road intersection density was positively associated with the number of bike-sharing uses (ß=0.43; P=.08). Among these, the lively perception showed the greatest independent effect (ß=1.29; P<.001), followed by the safety perception (ß=1.22; P=.001) and wealthy perception (ß=0.72; P=.001). The findings were robust in the three sensitivity analyses. Conclusions: A safer and livelier streetscape can enhance the benefits of land use mix in promoting bike-sharing use, with a safer streetscape also intensifying the effect of accessibility. Interventions focused on streetscape perceptions can encourage cycling behavior and enhance the benefits of accessibility and land use mix. This study also contributes to the literature on potential moderators of built environment healthy behavior associations from the perspective of microscale environmental perceptions.

Chaperone- and PTM-mediated activation of IRF1 tames radiation-induced cell death and the inflammatory response.

The key role of structural cells in immune modulation has been revealed with the advent of single-cell multiomics, but the underlying mechanism remains poorly understood. Here, we revealed that the transcriptional activation of interferon regulatory factor 1 (IRF1) in response to ionizing radiation, cytotoxic chemicals and SARS-CoV-2 viral infection determines the fate of structural cells and regulates communication between structural and immune cells. Radiation-induced leakage of mtDNA initiates the nuclear translocation of IRF1, enabling it to regulate the transcription of inflammation- and cell death-related genes. Novel posttranslational modification (PTM) sites in the nuclear localization sequence (NLS) of IRF1 were identified. Functional analysis revealed that mutation of the acetylation site and the phosphorylation sites in the NLS blocked the transcriptional activation of IRF1 and reduced cell death in response to ionizing radiation. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1, which restrains radiation-induced and STING/p300-mediated PTMs of IRF1, was revealed. In addition, genetic deletion or pharmacological inhibition of IRF1 tempered radiation-induced inflammatory cell death, and radiation mitigators also suppressed SARS-CoV-2 NSP-10-mediated activation of IRF1. Thus, we revealed a novel cytoplasm-oriented mechanism of IRF1 activation in structural cells that promotes inflammation and highlighted the potential effectiveness of IRF1 inhibitors against immune disorders.

Central Metal-Triggered Structural Transformation of a 2D Layered MOF: Mechanistic Studies and Applications.

The structural transformation of metal-organic frameworks (MOFs) has attracted increasing interests, which has not only produced various new structures but also served as a fantastic platform for MOF-based kinetic analysis. Multiple reaction conditions have been documented to cause structural transformation; nevertheless, central metal-induced topological alteration of MOFs is rare. Herein, we reported a structural transformation of a 2D layered Cd-MOF driven by Cd(II) ions. After being submerged in the aqueous solution of cadmium nitrate, the twofold interpenetrated 2D network of [Cd(hsb-2)(bdc)·5H2O]n [HSB-W10; bdc: 1,4-benzenedicarboxylate; hsb-2:1,2-bis(4'-pyridylmethylamino)-ethane] was converted into a novel noninterpenetrated 2D network [Cd1.5(hsb-2)(bdc)1.5(H2O)2·H2O]n (HSB-W16). This partial dissolution-recrystallization process was investigated by integrating controlled experiments, 1H NMR spectra, and photographic tracking analysis. Furthermore, a novel strategy combining in situ multicomponent dye encapsulation and central metal-triggered structural transformation was developed for the fabrication of MOF materials with white-light emission. By adopting this strategy, different dye guest molecules were concurrently introduced into the HSB-W16 host matrix, leading to a range of white-light-emitting MOF composites. This work will enable detailed studies of solid-state transformations and demonstrate a promising application prospect for structural transformation.

Regioselective Electrooxidative [3+2] Annulation between Indole and Aniline Derivatives to Construct Functionalized Indolo[2,3-b]indoles.

A protocol for the electrooxidative [3+2] annulation to generate indolo[2,3-b]indoles in an undivided cell is reported. It exhibits good yields with excellent regioselectivities and tolerates various functional groups without external chemical oxidants. Cyclic voltammetry and density functional theory calculations indicate that the [3+2] annulation is initiated by the simultaneous anodic oxidation of indole and aniline derivatives, and the step to determine the rate relies on the combination of radical cations.

A tumor-targeting two-photon fluorescent probe with a far-red to NIR emission for imaging basal hypochlorite in cancer cells and tumor.

Cancer cells have a high abundance of hypochlorite compared to normal cells, which can be used as the biomarker for imaging cancer cells and tumor. Developing the tumor-targeting fluorescent probe suitable for imaging hypochlorite in vivo is urgently demanded. In this article, based on xanthene dye with a two-photon excited far-red to NIR emission, a tumor-targeting two-photon fluorescent probe (Biotin-HClO) for imaging basal hypochlorite in cancer cells and tumor was developed. For ClO-, Biotin-HClO (20.0 µM) has a linear response range from 15.0 × 10-8 to 1.1 × 10-5 M with a high selectivity and a high sensitivity, a good detection limit of 50 nM and a 550-fold fluorescence enhancement with high signal-to-noise ratio (20 mM PBS buffer solution with 50 % DMF; pH = 7.4; λex = 605 nm; λem = 635 nm). Morover, Biotin-HClO exhibited excellent performance in monitoring exogenous and endogenous ClO- in cells, and has an outstanding tumor-targeting ability. Subsequently, Biotin-HClO has been applied for imaging ClO- in 4T1 tumor tissue to distinguish from normal tissue. Furthermore, Biotin-HClO was successfully employed for high-contrast imaging 4T1 tumor in mouse based on its tumor-targeting ability. All these results proved that Biotin-HClO is a useful analytical tool to detect ClO- and image tumor in vivo.

UV radiation-induced peptides in frog skin confer protection against cutaneous photodamage through suppressing MAPK signaling.

Overexposure to ultraviolet light (UV) has become a major dermatological problem since the intensity of ultraviolet radiation is increasing. As an adaption to outside environments, amphibians gained an excellent peptide-based defense system in their naked skin from secular evolution. Here, we first determined the adaptation and resistance of the dark-spotted frogs (Pelophylax nigromaculatus) to constant ultraviolet B (UVB) exposure. Subsequently, peptidomics of frog skin identified a series of novel peptides in response to UVB. These UV-induced frog skin peptides (UIFSPs) conferred significant protection against UVB-induced death and senescence in skin cells. Moreover, the protective effects of UIFSPs were boosted by coupling with the transcription trans-activating (TAT) protein transduction domain. In vivo, TAT-conjugated UIFSPs mitigated skin photodamage and accelerated wound healing. Transcriptomic profiling revealed that multiple pathways were modulated by TAT-conjugated UIFSPs, including small GTPase/Ras signaling and MAPK signaling. Importantly, pharmacological activation of MAPK kinases counteracted UIFSP-induced decrease in cell death after UVB exposure. Taken together, our findings provide evidence for the potential preventive and therapeutic significance of UIFSPs in UV-induced skin damage by antagonizing MAPK signaling pathways. In addition, these results suggest a practicable alternative in which potential therapeutic agents can be mined from organisms with a fascinating ability to adapt.