BpTCP19 targets BpWRKY53 to negatively regulate jasmonic acid- and dark-induced leaf senescence in Betula platyphylla.

TCP (TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1) is a plant-specific transcription factor that has garnered significant attention due to its wide-ranging involvement in the regulation of plant growth or developmental processes. However, the molecular mechanisms through which TCP genes orchestrate leaf senescence have not been extensively elucidated. BpTCP19, a member of the PCF subfamily in Betula platyphylla, and has high homology to AtTCP19. BpTCP19 displayed pronounced downregulation in response to methyl jasmonate (MeJA) and dark treatment. Overexpressing BpTCP19 in Betula platyphylla led to a delay in leaf senescence, resulting in prolonged leaf greenness under both MeJA and dark conditions. Transcriptome analysis revealed that overexpression of BpTCP19 induced alterations in the expression levels of genes linked to cell proliferation, hormone signaling transduction, and leaf senescence, including the early responsive factor BpWRKY53. Furthermore, through Yeast one-hybrid assays and GUS analysis, BpTCP19 was shown to bind to the promoter region of BpWRKY53, suppressing its expression and thereby retarding leaf senescence. This study elucidates the physiological and molecular functions of BpTCP19 as a central transcriptional regulatory module in leaf senescence and provides a potential target gene for delaying leaf senescence by mitigating sensitivity to external aging signals such as Jasmonic acid (JA) and darkness.

Notch4 regulatory T cells and SARS-CoV-2 viremia shape COVID19 survival outcome.

BACKGROUND: Immune dysregulation and SARS-CoV-2 plasma viremia have been implicated in fatal COVID-19 disease. However, how these two factors interact to shape disease outcomes is unclear. METHODS: We carried out viral and immunological phenotyping on a prospective cohort of 280 patients with COVID-19 presenting to acute care hospitals in Boston, Massachusetts and Genoa, Italy between June 1, 2020 and February 8, 2022. Disease severity, mortality, plasma viremia, and immune dysregulation were assessed. A mouse model of lethal H1N1 influenza infection was used to analyze the therapeutic potential of Notch4 and pyroptosis inhibition in disease outcome. RESULTS: Stratifying patients based on %Notch4+ Treg cells and/or the presence of plasma viremia identified four subgroups with different clinical trajectories and immune phenotypes. Patients with both high %Notch4+ Treg cells and viremia suffered the most disease severity and 90-day mortality compared to the other groups even after adjusting for baseline comorbidities. Increased Notch4 and plasma viremia impacted different arms of the immune response in SARS-CoV-2 infection. Increased Notch4 was associated with decreased Treg cell amphiregulin expression and suppressive function whereas plasma viremia was associated with increased monocyte cell pyroptosis. Combinatorial therapies using Notch4 blockade and pyroptosis inhibition induced stepwise protection against mortality in a mouse model of lethal H1N1 influenza infection. CONCLUSIONS: The clinical trajectory and survival outcome in hospitalized patients with COVID-19 is predicated on two cardinal factors in disease pathogenesis: viremia and Notch4+ Treg cells. Intervention strategies aimed at resetting the immune dysregulation in COVID-19 by antagonizing Notch4 and pyroptosis may be effective in severe cases of viral lung infection.

Review of Janus Kinase Inhibitors as Therapies for Noninfectious Uveitis.

Uveitis remains one of the leading causes of blindness worldwide, with different etiologies requiring separate approaches to treatment. For over a decade, oral, topical, and local injection of corticosteroids as well as systemic conventional disease-modifying antirheumatic drugs (DMARDs) have remained the most effective treatment for noninfectious uveitis (NIU). Systemic administration of antitumor necrosis factor-α and other biological DMARDs have been used for treating cases that responded inadequately to conventional treatments. Unfortunately, some refractory patients still suffer from frequent attacks despite the combination of multiple treatments. Recently, there has been promising evidence for Janus kinase (JAK) inhibitors as the next-generation therapy for NIU. The JAK/signal transducers and activators of the transcription (STAT) signaling pathway mediate the downstream events involved in immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis by binding various ligands, such as cytokines, growth hormones, and growth factors. The mutation or loss of JAK/STAT components is implicated in autoimmune diseases, thus inhibition of such pathways has been an important area of research in therapeutic development.1 In this review, we provide a comprehensive overview of the efficacy and safety of JAK inhibitors for the management of NIU, with evidence from current trials and case reports.

Rodent model of metabolic dysfunction-associated fatty liver disease: a systematic review.

Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.

Fluxional Behavior and Stability of the Cu2B8- Cluster: A Copper Borozene with a Freely Rotating Cu2 Dimer.

We demonstrate that Cu2B8- exhibits distinct fluxional behavior, akin to that of a functional stirrer, with the Cu2 dimer freely rotating on the B8 molecular wheel. This behavior is confirmed by Born-Oppenheimer molecular dynamics simulations. The initiation of this dynamic motion is facilitated by an ultrasoft vibrational mode (less than 10 cm-1), resulting in a negligible rotational barrier of 0.03 kcal/mol, as calculated at the single-point CCSD(T) level. The high stability of Cu2B8- arises from the strong interlayer electrostatic interaction between Cu2 and B8, due to charge transfer from Cu2 to B8, along with additional covalent interactions from the delocalized π electrons of the B8 wheel to the Cu2 dimer. Notably, the Cu2 dimer in Cu2B8- features a two-center one-electron Cu-Cu single bond, while the B82- moiety displays double aromaticity, characterized by the presence of six delocalized π electrons and six delocalized σ electrons.

Structural and excitonic properties of the polycrystalline FAPbI3thin films, and their photovoltaic responses.

Faormamadinium based perovskites have been proposed to replace the methylammonium lead tri-iodide (MAPbI3) perovskite as the light absorbing layer of photovoltaic cells owing to their photo-active and chemically stable properties. However, the crystal phase transition from the photo-activeα-FAPbI3to the non-perovksiteδ-FAPbI3still occurs in un-doped FAPbI3films owing to the existence of crack defects, which degrads the photovoltaic responses. To investigate the crack ratio (CR)-dependent structure and excitonic characteristics of the polycrystalline FAPbI3thin films deposited on the carboxylic acid functionalized ITO/glass substrates, various spectra and images were measured and analyzed, which can be utilized to make sense of the different devices responses of the resultant perovskite based photovoltaic cells. Our experimental results show that the there is a trade-off between the formations of surface defects and trapped iodide-mediated defects, thereby resulting in an optimal crack density or CR of the un-dopedα-FAPbI3active layer in the range from 4.86% to 9.27%. The decrease in the CR (tensile stress) results in the compressive lattice and thereby trapping the iodides near the PbI6octahedra in the bottom region of the FAPbI3perovskite films. When the CR of the FAPbI3film is 8.47%, the open-circuit voltage (short-circuit current density) of the resultant photovoltaic cells significantly increased from 0.773 V (16.62 mA cm-2) to 0.945 V (18.20 mA cm-2) after 3 d. Our findings help understanding the photovoltaic responses of the FAPbI3perovskite based photovoltaic cells on the different days.

Healthcare failure mode and effect analysis combined service blueprint - Mitigating mass casualty triage in emergency units: A qualitative study.

INTRODUCTION: The 24-hour operation of medical emergency units involves crucial first-hand information and medical treatments, which could involve potential complications and disputes if not handled with the utmost professionalism. Effective logistical support and timely activation are crucial in mass casualty triage to prevent systematic treatment issues and chaos. OBJECTIVE: This study explores the integration of Healthcare Failure Mode and Effect Analysis (HFMEA) with a service blueprint to mitigate medical risks and enhance mass casualty triage efficiency in emergency units. METHOD: An expert team analyzed emergency unit standard operating procedure cases using a service blueprint to visually represent mass casualty triage scenarios. The HFMEA identified potential hazards and failure risks in healthcare service delivery during mass casualty triage. RESULTS: Fifteen high-risk hazard indexes exceeding the standard score of eight were identified among three main processes and thirty-one potential failure reasons. The initial operational time for mass casualty triage was approximately 104 min, significantly reduced to 34 min after process revision (p = 0.043, <0.05). CONCLUSIONS: This study demonstrates effective time management in mass casualty triage, potentially saving up to an hour. Improved operational efficiency allows for focused resuscitation efforts, alleviating concerns about timely patient flow initiation.

Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.

Copper-catalyzed tandem cyclization reaction of ethynylbenzoxazinones and thiols: facile construction of 2-thiomethylene indoles.

The first successful copper-catalyzed decarboxylative cyclization reaction of ethynylbenzoxazinones and thiols has been developed. A rarely studied α-addition process to a copper-allenylidene intermediate promoted this reaction. Using this protocol, a range of 2-thiomethylene indole compounds have been obtained. This methodology offers significant advantages including mild reaction conditions, cheap catalysts, good yields and broad substrate compatibility.

Evaluating TRAIL and IP-10 alterations in vaccinated pregnant women after COVID-19 diagnosis and their correlation with neutralizing antibodies.

Background: This study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers. Methods: We studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns' blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors. Results: Our study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level. Conclusions: Our study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.