Structural basis for the conformational protection of nitrogenase from O.

The low reduction potentials required for the reduction of dinitrogen (N) render metal-based nitrogen-fixation catalysts vulnerable to irreversible damage by dioxygen (O). Such O sensitivity represents a major conundrum for the enzyme nitrogenase, as a large fraction of nitrogen-fixing organisms are either obligate aerobes or closely associated with O-respiring organisms to support the high energy demand of catalytic N reduction. To counter O damage to nitrogenase, diazotrophs use O scavengers, exploit compartmentalization or maintain high respiration rates to minimize intracellular O concentrations.

Studies on Shielding and Activation Levels in a Concrete-Iron-Concrete Sandwich Structure Wall in the CMUH Proton Therapy Facility.

The shielding performance and activation susceptibility of a sandwich wall in the proton therapy facility of China Medical University Hospital were investigated in an integrated manner using FLUKA Monte Carlo simulations. The 2-m-thick partition wall between two adjoining treatment rooms had a three-layered structure, which comprised a 0.2-m-thick iron layer sandwiched between two layers of 0.

Oncogenic RARγ isoforms promote head and neck cancer proliferation through vinexin-β-mediated cell cycle acceleration and autocrine activation of EGFR signal.

Results of retinoid-based therapies in head and neck cancer (HNC) are generally disappointing, indicating a lack of understanding of retinoic acid signaling. The role of retinoic acid receptor gamma (RARγ) and its isoforms in HNC is yet to be established. In this study, we found that RARγ1, 2, 4 are the predominant RARγ isoforms expressed in various types of human cancers, including HNC.

Online Child Sexual Exploitation and the Role of Computer-Mediated Communication: A Scoping Review.

The online landscape has shifted since the rise of smartphones and social media in the 2010s and altered the way children use technologies. Along with a reliance on computer-mediated communication (CMC) is the concern of online child sexual exploitation (OCSE). This scoping review provided an updated examination of the prevalence, risk factors, outcomes, and disclosures of OCSE since 2010.

Syngeneic mesenchymal stem cells loaded with telomerase-dependent oncolytic adenoviruses enhance anti-metastatic efficacy.

Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites.

Panoply of P: An Array of Rhenium-Phosphorus Complexes Generated from a Transition Metal Anion.

We expand upon the synthetic utility of anionic rhenium complex Na[(BDI)ReCp] (, BDI = -bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate) to generate several rhenium-phosphorus complexes. Complex reacts in a metathetical manner with chlorophosphines PhPCl, NHP-Cl, and OHP-Cl to generate XL-type phosphido complexes , , and , respectively (NHP-Cl = 2-chloro-1,3-dimethyl-1,3,2-diazaphospholidine; OHP-Cl = 2-chloro-1,3,2-dioxaphospholane). Crystallographic and computational investigations of phosphido triad , , and reveal that increasing the electronegativity of the phosphorus substituent (C < < O) results in a shortening and strengthening of the rhenium-phosphorus bond.

Neoantigen-augmented iPSC cancer vaccine combined with radiotherapy promotes antitumor immunity in poorly immunogenic cancers.

Although irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy.

Colorectal cancer-specific IFNβ delivery overcomes dysfunctional dsRNA-mediated type I interferon signaling to increase the abscopal effect of radiotherapy.

Background: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC.

Early Growth Response Protein 1 Exacerbates Murine Inflammatory Bowel Disease by Transcriptional Activation of Matrix Metalloproteinase 12.

Inflammatory bowel disease (IBD) is an inflammatory condition affecting the colon and small intestine, with Crohn's disease and ulcerative colitis being the major types. Individuals with long-term IBD are at an increased risk of developing colorectal cancer. Early growth response protein 1 (Egr1) is a nuclear protein that functions as a transcriptional regulator.

The Role of Wait Time During the Questioning of Children: A Systematic Review.

The benefits of wait time in classroom discourses have been well documented in the field of education since the 1970s. While current forensic interview guidelines recognize the importance of pauses, whether there is sufficient empirical evidence to inform wait time guidelines in the legal context remains unanswered. This systematic review aimed to synthesize and provide a holistic update on the available research on the role of wait time when questioning children and recommended future direction to develop wait time guidelines specific to child forensic interviews.

Control of cell proliferation by memories of mitosis.

Mitotic duration is tightly constrained, and extended mitosis is characteristic of problematic cells prone to chromosome missegregation and genomic instability. We show here that mitotic extension leads to the formation of p53-binding protein 1 (53BP1)-ubiquitin-specific protease 28 (USP28)-p53 protein complexes that are transmitted to, and stably retained by, daughter cells. Complexes assembled through a Polo-like kinase 1-dependent mechanism during extended mitosis and elicited a p53 response in G that prevented the proliferation of the progeny of cells that experienced an approximately threefold extended mitosis or successive less extended mitoses.

Redox Processes Involving Oxygen: The Surprising Influence of Redox-Inactive Lewis Acids.

Metalloenzymes with heteromultimetallic active sites perform chemical reactions that control several biogeochemical cycles. Transformations catalyzed by such enzymes include dioxygen generation and reduction, dinitrogen reduction, and carbon dioxide reduction-instrumental transformations for progress in the context of artificial photosynthesis and sustainable fertilizer production. While the roles of the respective metals are of interest in all these enzymatic transformations, they share a common factor in the transfer of one or multiple redox equivalents.

Dual Inhibition of B7-H3 and EGFR Overcomes Acquired Chemoresistance in Colon Adenocarcinoma.

Despite advances in therapeutic strategies for colorectal cancer (CRC), CRC has a high disease incidence with significant morbidity and mortality worldwide. Notably, immunotherapy has shown limited efficacy in treating metastatic CRC, underscoring the need for alternative immunotherapeutic targets for the management of metastatic colorectal cancer (mCRC). In the present study, we evaluated the levels of the immune checkpoint proteins PD-L1, PD-L2 and B7-H3 in a large cohort retrospective study.

Prothymosin α accelerates dengue virus-induced thrombocytopenia.

Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants.

Oct4 and Hypoxia Dual-Regulated Oncolytic Adenovirus Armed with shRNA-Targeting Dendritic Cell Immunoreceptor Exerts Potent Antitumor Activity against Bladder Cancer.

Immunotherapy has emerged as a promising modality for cancer treatment. Dendritic cell immunoreceptor (DCIR), a C-type lectin receptor, is expressed mainly by dendritic cells (DCs) and mediates inhibitory intracellular signaling. Inhibition of DCIR activation may enhance antitumor activity.

Shielding analysis of the proton therapy facility at China Medical University Hospital: comparison of a simplified approach with Monte Carlo simulations.

This study comprehensively compared two approaches for analyzing the shielding design of the proton therapy facility at China Medical University Hospital. The first approach essentially involved two approximate models: one for estimating the transmitted radiation through thick shields, and one for estimating radiation streaming at locations near a maze entrance. The second approach relied on Monte Carlo simulations for predicting the radiation field in a complex environment.

Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

Background: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD).

Molnupiravir, a ribonucleoside antiviral prodrug against SARS-CoV-2, alters the voltage-gated sodium current and causes adverse events.

Molnupiravir (MOL) is a ribonucleoside prodrug for oral treatment of COVID-19. Common adverse effects of MOL are headache, diarrhea, and nausea, which may be associated with altered sodium channel function. Here, we investigated the effect of MOL on voltage-gated Na current (I) in pituitary GH cells.

Amelioration of Murine Colitis by Attenuated Encoding Interleukin-19.

The imbalance of mucosal immunity in the lower gastrointestinal tract can lead to chronic inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis. IBD is a chronic inflammatory disorder that causes small and/or large intestines ulceration. According to previous studies, recombinant interleukin (IL)-10 protein and genetically modified bacteria secreting IL-10 ameliorate dextran sulfate sodium (DSS)-induced colitis in mice.

Coordination Number in High-Spin-Low-Spin Equilibrium in Cluster Models of the S State of the Oxygen Evolving Complex.

The S state of the Oxygen Evolving Complex (OEC) of Photosystem II (PSII) shows high-spin (HS) and low-spin (LS) EPR signals attributed to distinct structures based on computation. Five-coordinate Mn centers are proposed in these species but are absent in available spectroscopic model complexes. Herein, we report the synthesis, crystal structure, electrochemistry, SQUID magnetometry, and EPR spectroscopy of a MnMnO cuboidal complex featuring five-coordinate Mn.

Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a β-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis.

Oral DNA vaccine adjuvanted with cyclic peptide nanotubes induced a virus-specific antibody response in ducklings against goose parvovirus.

Background: Cyclic peptide nanotubes (cPNTs) formed from the spontaneous beta-sheet stacking of peptide rings may serve as a safe and effective oral delivery vehicle/adjuvant for DNA vaccines.

Aim: In this study, we sought to determine if a DNA vaccine expressing the VP2 protein of goose parvovirus, adjuvanted with cPNTs, may elicit virus-specific antibody response through oral vaccination.

Material And Methods: Forty 20-day-old Muscovy ducks were randomly assigned to two groups of 20 ducks each and vaccinated.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD.