The CRL3KCTD10 ubiquitin ligase-USP18 axis coordinately regulates cystine uptake and ferroptosis by modulating SLC7A11.

SLC7A11 is a cystine transporter and ferroptosis inhibitor. How the stability of SLC7A11 is coordinately regulated in response to environmental cystine by which E3 ligase and deubiquitylase (DUB) remains elusive. Here, we report that neddylation inhibitor MLN4924 increases cystine uptake by causing SLC7A11 accumulation, via inactivating Cullin-RING ligase-3 (CRL-3). We identified KCTD10 as the substrate-recognizing subunit of CRL-3 for SLC7A11 ubiquitylation, and USP18 as SLC7A11 deubiquitylase. Upon cystine deprivation, the protein levels of KCTD10 or USP18 are decreased or increased, respectively, contributing to SLC7A11 accumulation. By destabilizing or stabilizing SLC7A11, KCTD10, or USP18 inversely regulates the cystine uptake and ferroptosis. Biologically, MLN4924 combination with SLC7A11 inhibitor Imidazole Ketone Erastin (IKE) enhanced suppression of tumor growth. In human breast tumor tissues, SLC7A11 levels were negatively or positively correlated with KCTD10 or USP18, respectively. Collectively, our study defines how SLC7A11 and ferroptosis is coordinately regulated by the CRL3KCTD10/E3-USP18/DUB axis, and provides a sound rationale of drug combination to enhance anticancer efficacy.

Novel compound heterozygous variants in FANCI cause premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established. Here, we screened the FANCI gene, which encodes a key component for FA pathway activation, in our whole-exome sequencing database of 1030 patients with idiopathic POI, and identified two pairs of novel compound heterozygous variants, c.[97C > T];[1865C > T] and c.[158-2A > G];[c.959A > G], in two POI patients, respectively. The missense variants did not alter FANCI protein expression and nuclear localization, apart from the variant c.158-2A > G causing abnormal splicing and leading to a truncated mutant p.(S54Pfs*5). Furthermore, the four variants all diminished FANCD2 ubiquitination levels and increased DNA damage under replication stress, suggesting that the FANCI variants impaired FA pathway activation and replication stress response. This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function.

Prolonged Early Exposure to a High-Fat Diet Augments the Adverse Effects on Neurobehavior and Hippocampal Neuroplasticity: Involvement of Microglial Insulin Signaling.

High-fat diet (HFD) consumption may contribute to the high prevalence of cognitive-emotional issues in modern society. Mice fed a HFD for a prolonged period develop more severe neurobehavioral disturbances when first exposed to a HFD in the juvenile period than in adulthood, suggesting an initial age-related difference in the detrimental effects of long-term HFD feeding. However, the mechanism underlying this difference remains unclear. Here, male C57BL/6J mice initially aged 4 (IA4W) or 8 (IA8W) weeks were fed a control diet (CD) or HFD for 6 months and then subjected to metabolic, neurobehavioral, and histomorphological examinations. Although the detrimental effects of long-term HFD feeding on metabolism and neurobehavior were observed in mice of both ages, IA4W-HFD mice showed significant cognitive inflexibility accompanied by significantly greater levels of anxiety-like behavior than age-matched controls. Hippocampal neuroplasticity and microglial phenotype were altered by HFD feeding, whereas significant morphological alterations were more frequently observed in IA4W-HFD mice than in IA8W-HFD mice. Additionally, significantly increased hippocampal microglial engulfment of postsynaptic proteins and elevated phospho-insulin-receptor levels were observed in IA4W-HFD, but not in IA8W-HFD, mice. These findings suggest that aberrant microglia-related histomorphological changes in the hippocampus underlie the exacerbated detrimental neurobehavioral effects of prolonged early HFD exposure and indicate that enhanced insulin signaling might drive microglial dysfunction after prolonged early HFD exposure.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Assembly patterns and key taxa of bacterial communities in the rhizosphere soil of moso bamboo (Phyllostachys pubescens) under different Cd and Pb pollution.

Moso bamboo is excellent candidate for cadmium (Cd)/lead (Pb) phytoremediation, while rhizosphere microbiome has significant impact on phytoremediation efficiency of host plant. However, little is known about the rhizosphere bacterial communities of moso bamboo in Cd/Pb contaminated soils. Therefore, this study investigated the assembly patterns and key taxa of rhizosphere bacterial communities of moso bamboo in Cd/Pb polluted and unpolluted soils, by field sampling, chemical analysis, and 16S rRNA gene sequencing. The results indicated α-diversity between Cd/Pb polluted and unpolluted soils showed a similar pattern (p > 0.05), while ß-diversity was significantly different (p < 0.05). The relative abundance analysis indicated α-proteobacteria (37%) and actinobacteria (31%) were dominant in Cd/Pb polluted soils, while γ-proteobacteria (40%) and α-proteobacteria (22%) were dominant in unpolluted soils. Co-occurrence network analysis indicated microbial networks were less complex and more negative in polluted soils than in unpolluted soils. Mantel analysis indicated soil available phosphorus, organic matter, and available Pb were the most important environmental factors affecting microbial community structure. Correlation analysis showed 11 bacterial genera were significantly positively related to Cd/Pb. Overall, this study identified the bacterial community composition of bamboo rhizosphere in responding to Cd/Pb contamination and provides a theoretical basis for microbe-assistant phytoremediation in the future.

To date, little is known about the bacterial communities in the rhizosphere of moso bamboo under Cd and Pb multiple stresses. This study investigated the assembly patterns and key taxa of rhizospheric bacterial communities of moso bamboo in Cd/Pb polluted and unpolluted soils. It was found that the bacterial community structure in bamboo rhizosphere is easily influenced by soil chemical environment, such as fertilities and heavy metals. The key bacterial taxa identified here could be target microbe in future microbe-assistant phytoremediation.

(D-Ala2)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-α and RANKL Expression and Directly Impeding Osteoclast Formation.

Glucose-insulinotropic polypeptide (GIP) is an incretin hormone that induces insulin secretion and decreases blood glucose levels. In addition, it has been reported to suppress osteoclast formation. Native GIP is rapidly degraded by dipeptidyl peptidase-4 (DPP-4). (D-Ala2)GIP is a newly developed GIP analog that demonstrates enhanced resistance to DPP-4. This study aimed to evaluate the influence of (D-Ala2)GIP on osteoclast formation and bone resorption during lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. In vivo, mice received supracalvarial injections of LPS with or without (D-Ala2)GIP for 5 days. Osteoclast formation and bone resorption were evaluated, and TNF-α and RANKL expression were measured. In vitro, the influence of (D-Ala2)GIP on RANKL- and TNF-α-induced osteoclastogenesis, LPS-triggered TNF-α expression in macrophages, and RANKL expression in osteoblasts were examined. Compared to the LPS-only group, calvariae co-administered LPS and (D-Ala2)GIP led to less osteoclast formation, lower bone resorption, and decreased TNF-α and RANKL expression. (D-Ala2)GIP inhibited osteoclastogenesis induced by RANKL and TNF-α and downregulated TNF-α expression in macrophages and RANKL expression in osteoblasts in vitro. Furthermore, (D-Ala2)GIP suppressed the MAPK signaling pathway. The results suggest that (D-Ala2)GIP dampened LPS-triggered osteoclast formation and bone resorption in vivo by reducing TNF-α and RANKL expression and directly inhibiting osteoclastogenesis.

Integrated Uniformly Microporous C4 N/Multi-Walled Carbon Nanotubes Composite Toward Ultra-Stable and Ultralow-Temperature Proton Batteries.

Benefiting from the proton's small size and ultrahigh mobility in water, aqueous proton batteries are regarded as an attractive candidate for high-power and ultralow-temperature energy storage devices. Herein, a new-type C4 N polymer with uniform micropores and a large specific surface area is prepared by sulfuric acid-catalyzed ketone amine condensation reaction and employed as the electrode of proton batteries. Multi-walled carbon nanotubes (MWCNT) are introduced to induce the in situ growth of C4 N, and reaped significantly enhanced porosity and conductivity, and thus better both room- and low-temperature performance. When coupled with MnO2 @Carbon fiber (MnO2 @CF) cathode, MnO2 @CF//C4 N-50% MWCNT full battery shows unprecedented cycle stability with a capacity retention of 98% after 11 000 cycles at 10 A g-1 and even 100% after 70 000 cycles at 20 A g-1 . Additionally, a novel anti-freezing electrolyte (5 m H2 SO4  + 0.5 m MnSO4 ) is developed and showed a high ionic conductivity of 123.2 mS cm-1 at -70 °C. The resultant MnO2 @CF//C4 N-50% MWCNT battery delivers a specific capacity of 110.5 mAh g-1 even at -70 °C at 1 A g-1 , the highest in all reported proton batteries under the same conditions. This work is expected to offer a package solution for constructing high-performance ultralow-temperature aqueous proton batteries.

Enhanced generation of oxysulfur radicals by the BiOBr/Montmorillonite activated sulfite system: Performance and mechanism.

The easily synthesized, cost-effective, and stable photocatalysts for sulfite activation are always required for the enhancement of organic contaminants degradation. Herein, the facile coprecipitation synthesis of Bismuth oxybromide (BiOBr)/Montmorillonite (MMT) was reported, which could activate sulfite (SO32-/HSO3-) under sunlight and accelerate the catalytic performance more effectively than pristine BiOBr. After adding sulfite to the photocatalysis system, the photodegradation efficiency of atrazine (ATZ) achieved 73.7% ± 1.5% after 5 min and 94.4% ± 1.6% after 30 min of sunlight irradiation with BiOBr/MMT. The BiOBr/MMT-sulfite system also presented remarkable photocatalytic performance to eliminate various contaminants, including ciprofloxacin, sulfadiazine, tetracycline, and carbamazepine. The various features of the photocatalyst materials were studied, including their surface morphology, structure, optical properties, and composition. The results illustrated that by adding MMT, the bandgap of the pristine BiOBr was reduced and the surface area was increased, which led to an increased ability to adsorb materials. Results of various influence factors showed this enhanced system had satisfactory and stable removal performance of ATZ in the pH range of 3.0-6.5, but HPO42- had a strong negative effect on the system performance. Oxysulfur radicals (SO5·- and SO4·-), h+, and 1O2 were discovered as the prevailing active species in the BiOBr/MMT-sulfite system. The proposed degradation mechanism of this photocatalyst-enhanced system revealed that sulfite adsorption on the surface of the photocatalyst played a vital role during the initial phase, and the degradation pathway of ATZ was discussed. This study provides a new synthesis strategy of a photocatalyst for sulfite activation and expands the potential uses of Bi-based photocatalysts in degrading difficult-to-remove organic pollutants.

High-Fat Diet Consumption Induces Neurobehavioral Abnormalities and Neuronal Morphological Alterations Accompanied by Excessive Microglial Activation in the Medial Prefrontal Cortex in Adolescent Mice.

The association between a high-fat diet (HFD) consumption and emotional/cognitive disorders is widely documented. One distinctive feature of the prefrontal cortex (PFC), a kernel emotion- and cognition-related brain region, is its protracted adolescent maturation, which makes it highly vulnerable to the detrimental effects of environmental factors during adolescence. Disruption of the PFC structure and function is linked to emotional/cognitive disorders, especially those that emerge in late adolescence. A HFD consumption is common among adolescents, yet its potential effects on PFC-related neurobehavior in late adolescence and any related underlying mechanisms are yet to be established. In the present study, adolescent (postnatal days 28-56) male C57BL/6J mice were fed a control diet (CD) or a HFD and underwent behavioral tests in addition to Golgi staining and immunofluorescence targeting of the medial PFC (mPFC). The HFD-fed adolescent mice exhibited anxiety- and depression-like behavior and abnormal mPFC pyramidal neuronal morphology accompanied by alterations in microglial morphology indicative of a heightened state of activation and increased microglial PSD95+ inclusions signifying excessive phagocytosis of the synaptic material in the mPFC. These findings offer novel insights into the neurobehavioral effects due to adolescent HFD consumption and suggest a contributing role in microglial dysfunction and prefrontal neuroplasticity deficits for HFD-associated mood disorders in adolescents.

Generating Bone Marrow Chimeric Mouse Using GPR120 Deficient Mouse for the Study of DHA Inhibitory Effect on Osteoclast Formation and Bone Resorption.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that exerts physiological effects via G protein-coupled receptor 120 (GPR120). In our previous studies, we figured out the inhibitory effects of DHA on TNF-α (Tumor necrosis factor-α)-induced osteoclastogenesis via GPR120 in vivo. Moreover, DHA directly suppressed RANKL expression in osteoblasts via GPR120 in vitro. In this study, we generated bone marrow chimeric mice using GPR120 deficient mice (GPR120-KO) to study the inhibitory effects of DHA on bone resorption and osteoclast formation. Bone marrow cells of wild-type (WT) or GPR120-KO mice were transplanted into irradiated recipient mice, which were WT or GPR120 deficient mice. The resulting chimeric mice contained stromal cells from the recipient and bone marrow cells, including osteoclast precursors, from the donor. These chimeric mice were used to perform a series of histological and microfocus computed tomography (micro-CT) analyses after TNF-α injection for induction of osteoclast formation with or without DHA. Osteoclast number and bone resorption were found to be significantly increased in chimeric mice, which did not express GPR120 in stromal cells, compared to chimeric mice, which expressed GPR120 in stromal cells. DHA was also found to suppress specific signaling pathways. We summarized that DHA suppressed TNF-α-induced stromal-dependent osteoclast formation and bone resorption via GPR120.

Reorganization of Hydrogen Bonding in Biobased Polyamide 5,13 under the Thermo-Mechanical Field: Hierarchical Microstructure Evolution and Achieving Excellent Mechanical Performance.

The hierarchical microstructure evolution of an emerging biobased odd-odd polyamide 5,13 (PA5,13) films under the thermo-mechanical field, stepping from hydrogen bond (H-bond) arrangement to the crystalline morphology, has been investigated systematically. It is found that the reorganization of H-bonds under the thermo-mechanical field plays a crucial role in the crystallization of PA5,13. Especially, it is revealed that the crystallization process under the thermo-mechanical field develops along the chain axis direction, while lamellar fragmentation occurs perpendicular to the chain axis. Consequently, a stable and well-organized H-bond arrangement and lengthened lamellae with significant orientation have been constructed. Laudably, an impressive tensile strength of about 500 MPa and modulus of about 4.7 GPa are thus achieved. The present study could provide important guidance for the industrial-scale manufacture of high-performance biobased odd-odd PAs with long polymethylene segment in the dicarboxylic unit combined with a large difference between the polymethylene segments in the dicarboxylic and diamine units.

Computational Simulation of HIV Protease Inhibitors to the Main Protease (Mpro) of SARS-CoV-2: Implications for COVID-19 Drugs Design.

SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro. However, the mechanism of action has still not been studied very clearly. In this work, the interaction mechanism of four HIV protease inhibitors Darunavir (DRV), Lopinavir (LPV), Nelfinavir (NFV), and Ritonavire (RTV) targeting SARS-CoV-2 Mpro was explored by applying docking, molecular dynamics (MD) simulations, and MM-GBSA methods using the broad-spectrum antiviral drug Ribavirin (RBV) as the negative and nonspecific control. Our results revealed that LPV, RTV, and NFV have higher binding affinities with Mpro, and they all interact with catalytic residues His41 and the other two key amino acids Met49 and Met165. Pharmacophore model analysis further revealed that the aromatic ring, hydrogen bond donor, and hydrophobic group are the essential infrastructure of Mpro inhibitors. Overall, this study applied computational simulation methods to study the interaction mechanism of HIV-1 protease inhibitors with SARS-CoV-2 Mpro, and the findings provide useful insights for the development of novel anti-SARS-CoV-2 agents for the treatment of COVID-19.

Molecular Docking and Molecular Dynamics (MD) Simulation of Human Anti-Complement Factor H (CFH) Antibody Ab42 and CFH Polypeptide.

An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.

A review and new perspective on oral bacteriophages: manifestations in the ecology of oral diseases.

Objective: To explore the manifestations of bacteriophages in different oral disease ecologies, including periodontal diseases, dental caries, endodontic infections, and oral cancer, as well as to propel phage therapy for safer and more effective clinical application in the field of dentistry. Methods: In this literature review, we outlined interactions between bacteriophages, bacteria and even oral cells in the oral ecosystem, especially in disease states. We also analyzed the current status and future prospects of phage therapy in the perspective of different oral diseases. Results: Various oral bacteriophages targeting at periodontal pathogens as Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola and Aggregatibacter actinomycetemcomitans, cariogenic pathogen Streptococcus mutans, endodontic pathogen Enterococcus faecalis were predicted or isolated, providing promising options for phage therapy. In the realm of oral cancer, aside from displaying tumor antigens or participating in tumor-targeted therapies, phage-like particle vaccines demonstrated the potential to prevent oral infections caused by human papillomaviruses (HPVs) associated with head-and-neck cancers. Conclusion: Due to their intricate interactions with bacteria and oral cells, bacteriophages are closely linked to the progression and regression of diverse oral diseases. And there is an urgent need for research to explore additional possibilities of bacteriophages in the management of oral diseases.

Protective effect of carbon dots as antioxidants on intestinal inflammation by regulating oxidative stress and gut microbiota in nematodes and mouse models.

Inflammatory bowel disease (IBD) is a recurrent chronic colitis disease with increasing incidence and prevalence year by year. The single efficacy and significant side effects of traditional IBD treatment drugs have promoted the flourishing development of new drugs. Inspired by many health benefits of carbon dots (CDs) based nanomedicine in biomedical applications, a metal-free carbon dots (CP-CDs) was synthesized from citric acid and polyethylene polyamine to treat colitis. Oxidative stress tests at the cellular and nematode levels demonstrated CP-CDs have good antioxidant effects, while the toxicity of CP-CDs to cells and nematodes is low. CP-CDs were further applied to dextran sodium sulfate (DSS)-induced colitis in mice models, and it was found that CP-CDs can reduce the disease activity index (DAI) score of colon tissue and restore the intestinal barrier. Further, the anti-colitis mechanisms of CP-CDs were explored, one of which is to regulate intestinal oxidative stress in inflammatory mice, further reducing the expression of inflammatory cytokines, and thus alleviating colitis. Notably, 16S rRNA sequence analysis showed that the abundance of beneficial bacteria (Ligilactobacillus and Enterorhabdus) in the intestinal tract increased, while that of harmful bacteria (unclassified_Clostridia_UCG_014) decreased after CP-CDs treatment, indicating that CP-CDs rebalancing the gut microbiota destroyed by DSS is another important mechanism. In short, these non-toxic carbon dots not only have the potential for multi-factor combined relief of colitis but also offer an alternative therapy medicine for patients suffering from IBD.

How urban heat island magnifies hot day exposure: Global unevenness derived from differences in built landscape.

Urban heat-islands reportedly expose densely populated areas to higher temperatures. However, the magnitude of the impact of extra hot-day exposure (EHDE) and its association with the effects of urbanization on a global scale remain unclear. As local climate zones (LCZs) refine the impact of differences in urban built-type on heat-island effects, this study aimed to quantify the global EHDE caused by the urban heat-island effect based on LCZs and explored the joint impacts of low gross-domestic product and an increasing vulnerable-age population on EHDE. The results showed that EHDE accounted for 48.01 % of overall hot-day exposure. Additionally, despite a significant geographic differentiation among LCZ types with the highest EHDE intensity, they are almost typically building-intensive LCZs. Furthermore, our study revealed regional differences in the structure of the EHDE share in LCZs, which support the adoption of targeted EHDE mitigation strategies.

Understanding the role of transition metal single-atom electronic structure in oxysulfur radical-mediated oxidative degradation.

The ubiquity of refractory organic matter in aquatic environments necessitates innovative removal strategies. Sulfate radical-based advanced oxidation has emerged as an attractive solution, offering high selectivity, enduring efficacy, and anti-interference ability. Among many technologies, sulfite activation, leveraging its cost-effectiveness and lower toxicity compared to conventional persulfates, stands out. Yet, the activation process often relies on transition metals, suffering from low atom utilization. Here we introduce a series of single-atom catalysts (SACs) employing transition metals on g-C3N4 substrates, effectively activating sulfite for acetaminophen degradation. We highlight the superior performance of Fe/CN, which demonstrates a degradation rate constant significantly surpassing those of Ni/CN and Cu/CN. Our investigation into the electronic and spin polarization characteristics of these catalysts reveals their critical role in catalytic efficiency, with oxysulfur radical-mediated reactions predominating. Notably, under visible light, the catalytic activity is enhanced, attributed to an increased generation of oxysulfur radicals and a strengthened electron donation-back donation dynamic. The proximity of Fe/CN's d-band center to the Fermi level, alongside its high spin polarization, is shown to improve sulfite adsorption and reduce the HOMO-LUMO gap, thereby accelerating photo-assisted sulfite activation. This work advances the understanding of SACs in environmental applications and lays the groundwork for future water treatment technologies.

Effect of age on orthodontic tooth movement in mice.

Background/purpose: The number of middle-aged and elderly orthodontic patients is increasing due to changes in age composition. It is important to investigate the detailed mechanisms of bone remodeling in orthodontic tooth movement (OTM) in the elderly. However, there are few reports on the mechanism of tooth movement in the elderly. The purpose of the present study was to analyze OTM and osteoclastogenesis in aged mice and to elucidate the mechanism. Materials and methods: It has been reported that tumor necrosis factor (TNF)-α plays an important role in osteoclast formation and OTM. First, 8-week-old and 78-week-old male C57BL/6J mice were subcutaneously injected with TNF-α into the calvaiae, and micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and real-time PCR were performed to evaluate osteoclast formation and bone resorption. Furthermore, osteoclastogenesis by TNF-α and receptor activator of nuclear factor-kappa B ligand (RANKL) using bone marrow cells was evaluated in vitro. Finally, a nickel-titanium closed-coil spring was attached, mesial movement of the maxillary left first molar was performed, and tooth movement distance and osteoclast formation were evaluated. Results: Compared to 8-week-old mice, 78-week-old mice had decreased TNF-α-induced bone resorption, osteoclastogenesis, and TRAP and cathepsin K expression in the calvariae. In vitro osteoclast formation also decreased in 78-week-old mice. Furthermore, tooth movement distance and osteoclastogenesis were reduced. Conclusion: OTM decreased in aged mice, which was shown to be caused by a decrease in osteoclastogenesis. Therefore, it was suggested that it is necessary to keep in mind that tooth movement may be suppressed when treating elderly patients.

Shared insights for heat health risk adaptation in metropolitan areas of developing countries.

Global warming has led to a surge in heat health risks (HHRs), the impacts of which are particularly pronounced in metropolitan areas of developing countries. In the current study, six metropolitan areas - Beijing, China; Cairo, Egypt; Jakarta, Indonesia; Mumbai, India; Rio de Janeiro, Brazil; and Tehran, Iran - were selected as the study area to further differentiate the built-up landscapes by utilizing the concept of local climate zones. Moreover, we assessed the similarities and differences in HHR associated with the landscape. Results revealed a 30.67% higher HHR in compact built-up landscapes than in the open built-up type. Urban green spaces played an effective but differentiated role in mitigating HHR. That is, low vegetation in urbanized areas and trees in suburban areas significantly mitigated HHR. Collectively, our findings emphasize the role of effective planning and management in addressing HHR and provide empirical support for implementing HHR mitigation and adaptation strategies.

Prevalence, clinical characteristics, and long-term outcomes of new diabetes diagnosis in elderly patients undergoing percutaneous coronary intervention.

Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24-2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29-3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09-2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94-2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population.