Overcoming the coupled climate and biodiversity crises and their societal impacts.

Earth's biodiversity and human societies face pollution, overconsumption of natural resources, urbanization, demographic shifts, social and economic inequalities, and habitat loss, many of which are exacerbated by climate change. Here, we review links among climate, biodiversity, and society and develop a roadmap toward sustainability. These include limiting warming to 1.5°C and effectively conserving and restoring functional ecosystems on 30 to 50% of land, freshwater, and ocean "scapes." We envision a mosaic of interconnected protected and shared spaces, including intensively used spaces, to strengthen self-sustaining biodiversity, the capacity of people and nature to adapt to and mitigate climate change, and nature's contributions to people. Fostering interlinked human, ecosystem, and planetary health for a livable future urgently requires bold implementation of transformative policy interventions through interconnected institutions, governance, and social systems from local to global levels.

Unconventional supercurrent phase in Ising superconductor Josephson junction with atomically thin magnetic insulator.

In two-dimensional (2D) NbSe2 crystal, which lacks inversion symmetry, strong spin-orbit coupling aligns the spins of Cooper pairs to the orbital valleys, forming Ising Cooper pairs (ICPs). The unusual spin texture of ICPs can be further modulated by introducing magnetic exchange. Here, we report unconventional supercurrent phase in van der Waals heterostructure Josephson junctions (JJs) that couples NbSe2 ICPs across an atomically thin magnetic insulator (MI) Cr2Ge2Te6. By constructing a superconducting quantum interference device (SQUID), we measure the phase of the transferred Cooper pairs in the MI JJ. We demonstrate a doubly degenerate nontrivial JJ phase (ϕ), formed by momentum-conserving tunneling of ICPs across magnetic domains in the barrier. The doubly degenerate ground states in MI JJs provide a two-level quantum system that can be utilized as a new dissipationless component for superconducting quantum devices. Our work boosts the study of various superconducting states with spin-orbit coupling, opening up an avenue to designing new superconducting phase-controlled quantum electronic devices.

Association of Periodontitis with Oral Cancer: A Case-Control Study.

The association between oral squamous cell carcinoma (OSCC) and periodontitis in large hospital cases with cohort controls has yet to be evaluated. The aim of this study was to investigate the association of periodontitis with OSCC across tumor location and tumor-node-metastasis (TNM) stage among Koreans ( N = 424). OSCC cases ( n = 146) were recruited from Seoul National University Dental Hospital and matched by age, sex, and smoking to controls ( n = 278) from the Yangpyeong health and periodontal cohort in Korea. OSCC was diagnosed through biopsy and radiographs, including computed tomography and magnetic resonance imaging. Tumor location and TNM stage were classified after the surgery. Periodontitis was defined by alveolar bone loss with panoramic radiographs following the guidelines of the Fifth European Workshop in Periodontology. Alcohol intake, education, physical activity, obesity by body mass index, hypertension by blood pressure, diabetes by plasma glucose, and hypercholesterolemia by plasma cholesterol were considered as confounders. Information about age, sex, smoking, alcohol intake, education, and physical activity was obtained through interview; body mass index and blood pressure, through physical examination; and preoperative glucose and cholesterol, through laboratory tests. Bivariate analysis was applied with Fisher's exact chi-square test. Multivariable conditional logistic regression models were applied to evaluate the adjusted association of periodontitis with OSCC after controlling for confounders. Subgroup analyses were explored by OSCC and periodontitis. Participants with periodontitis were 3.7 times more likely to have OSCC (adjusted odds ratio [aOR] = 3.66, 95% CI = 1.46 to 9.23) than participants without periodontitis. The differences in periodontitis were not statistically significant across TNM stages of OSCC ( P > 0.05) and its location ( P > 0.05). The link was highlighted among males (aOR = 6.55), elders aged >60 y (aOR = 4.98), and those with more tooth loss (aOR = 9.99). Our data showed that periodontitis was independently associated with OSCC. Thus, the risk of OSCC could be modulated by reducing periodontitis.

Identification of aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) as novel renal damage biomarkers following exposure to mercury.

The kidney is one of the main targets for toxicity induced by xenobiotics. Sensitive detection of early impairment is critical to assess chemical-associated renal toxicity. The aim of this study was to identify potential nephrotoxic biomarkers in rat kidney tissues after exposure to mercury (Hg), a representative nephrotoxicant, and to evaluate these new biomarkers employing in vivo and in vitro systems. Mercuric chloride was administered orally to Sprague-Dawley rats for 2 weeks. Proteomic analysis revealed that aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) were significantly elevated in kidney after Hg exposure. While the levels of conventional nephrotoxic clinical markers including blood urea nitrogen and serum creatinine were not elevated, the mRNA and protein levels of AKR7A1 and GSTP1 were increased upon Hg exposure in a dose-dependent manner. The increases in AKR7A1 and GSTP1 were also observed in rat kidneys after an extended exposure for 6 weeks to low-dose Hg. In in vitro rat kidney proximal tubular cells, changes in AKR7A1 and GSTP1 levels correlated well with the extent of cytotoxicity induced by Hg, cadmium, or cisplatin. AKR7A1 and GSTP1 were identified as new candidates for Hg-induced nephrotoxicity, suggesting that these biomarkers have potential for evaluating or predicting nephrotoxicity.

Foxp3 is a key downstream regulator of p53-mediated cellular senescence.

The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.

Direct penetration of spin-triplet superconductivity into a ferromagnet in Au/SrRuO3/Sr2RuO4 junctions.

Efforts have been ongoing to establish superconducting spintronics utilizing ferromagnet/superconductor heterostructures. Previously reported devices are based on spin-singlet superconductors (SSCs), where the spin degree of freedom is lost. Spin-polarized supercurrent induction in ferromagnetic metals (FMs) is achieved even with SSCs, but only with the aid of interfacial complex magnetic structures, which severely affect information imprinted to the electron spin. Use of spin-triplet superconductors (TSCs) with spin-polarizable Cooper pairs potentially overcomes this difficulty and further leads to novel functionalities. Here, we report spin-triplet superconductivity induction into a FM SrRuO3 from a leading TSC candidate Sr2RuO4, by fabricating microscopic devices using an epitaxial SrRuO3/Sr2RuO4 hybrid. The differential conductance, exhibiting Andreev-reflection features with multiple energy scales up to around half tesla, indicates the penetration of superconductivity over a considerable distance of 15 nm across the SrRuO3 layer without help of interfacial complex magnetism. This demonstrates potential utility of FM/TSC devices for superspintronics.

CT findings of post-polypectomy coagulation syndrome and colonic perforation in patients who underwent colonoscopic polypectomy.

AIM: To investigate the clinical characteristics and computed tomography (CT) findings of post-polypectomy coagulation syndrome (PPCS) and colonic perforation in patients who have undergone colonoscopic polypectomy. MATERIALS AND METHODS: Through a hospital database search, 5542 adult patients (age >40 years) who had undergone colonoscopic polypectomy from January 2011 to November 2014 were identified. After identification of patients with PPCS and colonic perforation, two abdominal radiologists reviewed the CT images of the patients in consensus. RESULTS: Eight patients (0.14%) with PPCS and six patients (0.11%) with perforation were identified. Five patients were excluded for absence of CT examination, leaving four patients with PPCS and five patients with perforation included in the study. Three of the patients with perforation eventually underwent surgery, while all the patients with PPCS completely recovered with conservative management. On CT images, the involved colonic wall was longer and thicker in the PPCS group than in the perforation group. All four patients with PPCS showed a mural defect filled with fluid and stratified enhancement with surrounding infiltration. Two patients, who did not undergo surgery for perforation, did not show surrounding infiltration and fluid collection. CONCLUSION: On CT images, PPCS shows severe mural thickening with a stratified enhancement pattern, a mural defect filled with fluid and surrounding infiltration in addition to absence of extraluminal air. In patients with perforation, absence of CT findings suggestive of surrounding inflammation or peritonitis would help in choosing non-surgical management.

Rapid enlargement of endometrial stromal sarcoma after uterine fibroid embolization for presumed adenomyosis: a case report and literature review.

Uterine sarcomas have rarely been diagnosed after uterine artery embolization. It remains unclear whether the diagnostic work-up is required prior to such embolization to prevent a missed diagnosis of sarcomas and a delay in providing definitive treatment. Because of the rarity and heterogeneity of endometrial stromal neoplasms, little is known about their epidemiology, pathogenesis, and molecular pathology. The authors report a case of low-grade endometrial stromal sarcoma (ESS) diagnosed after uterine fibroid embolization. Although they performed laparoscopic biopsy of the rapidly growing uterine mass, they could not detect the ESS. Although rare, ESS should be considered in the differential diagnosis of uterine fibroid enlargement. It is essential to assess the risk of malignancy by taking into account the patient's clinical symptoms, results of the physical exam, and imaging findings prior to uterine artery embolization. Pathologic diagnosis should include an adequate biopsy sample and the use of molecular genetic testing.

Suppression of creep-regime dynamics in epitaxial ferroelectric BiFeO3 films.

Switching dynamics of ferroelectric materials are governed by the response of domain walls to applied electric field. In epitaxial ferroelectric films, thermally-activated 'creep' motion plays a significant role in domain wall dynamics, and accordingly, detailed understanding of the system's switching properties requires that this creep motion be taken into account. Despite this importance, few studies have investigated creep motion in ferroelectric films under ac-driven force. Here, we explore ac hysteretic dynamics in epitaxial BiFeO3 thin films, through ferroelectric hysteresis measurements, and stroboscopic piezoresponse force microscopy. We reveal that identically-fabricated BiFeO3 films on SrRuO3 or La0.67Sr0.33MnO3 bottom electrodes exhibit markedly different switching behaviour, with BiFeO3/SrRuO3 presenting essentially creep-free dynamics. This unprecedented result arises from the distinctive spatial inhomogeneities of the internal fields, these being influenced by the bottom electrode's surface morphology. Our findings further highlight the importance of controlling interface and defect characteristics, to engineer ferroelectric devices with optimised performance.

Involvement of G-quadruplex structures in regulation of human RET gene expression by small molecules in human medullary thyroid carcinoma TT cells.

The RET (rearranged during transfection) proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signaling molecules. The activating germline point mutations in the RET, which are known to induce oncogenic activation of RET tyrosine kinase, are associated with the development of medullary thyroid carcinoma (MTC) and pathogenesis of multiple endocrine neoplasia type 2 (MEN2). The polypurine/polypyrimidine tract in the proximal promoter region of the human RET gene (-51 to -33 relative to transcription start site) is essential for basal transcriptional activity of this gene. This tract consists of a guanine-rich sequence containing five runs of at least three contiguous guanines separated by one or more bases, conforming to a general motif capable of forming an intramolecular G-quadruplex. Here, we show that specific G-quadruplex structures formed in the RET promoter region act to repress the transcription of this gene, and transcription of this gene can be controlled by ligand-mediated G-quadruplex stabilization. In this study, NSC194598, a derivative of indeno[1,2,3-de]quinazoline, was found to be a novel G-quadruplex interactive agent that interfered with transcriptional activation of mutated RET gene in human medullary thyroid carcinoma TT cells. This compound significantly reduced endogenous RET protein levels and increased apoptosis in these cells. Our results provide further support for the idea that G-quadruplex structures may have a critical role in transcriptional regulation of the RET gene in vivo, providing insight into a novel strategy for transcriptional repression of this gene by small molecules.

Prediction of subclinical atherosclerosis by serum osteoprotegerin in premenopausal women with systemic lupus erythematous: correlation of osteoprotegerin with monocyte chemotactic protein-1.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased risk for cardiovascular disease. Previous studies disclosed the association of serum osteoprotegerin (OPG) with the presence of symptomatic atherosclerosis in the general population and several disease conditions. We thus investigated the association between serum OPG levels and subclinical atherosclerosis in premenopausal SLE patients. METHODS: Serum OPG levels and carotid artery intima-media thickness (IMT) were measured in 181 premenopausal SLE patients and age-matched 85 control subjects. Traditional cardiovascular risk factors and SLE-related factors were analyzed. RESULTS: Patients with SLE had significantly increased serum OPG levels (1086 versus 517 pg/ml, p < 0.001) and carotid IMT (0.63 versus 0.45 mm, p < 0.001) compared with control subjects. Carotid IMT significantly increased across the quartiles of OPG. Logistic regression analysis revealed that compared to the lowest OPG quartile, the odds ratio (OR, 95% confidence interval) for increased carotid IMT in quartile 2, 3, and 4 was 1.126 (1.013-1.801), 1.562 (1.268-2.799), and 4.460 (1.126-7.128), respectively, after multiple adjustments (p for trend across quartiles < 0.001). These associations remained significant after further adjustment for inflammatory parameters. Interestingly, serum monocyte chemotactic protein-1 (MCP-1) levels were positively correlated with serum OPG levels (γ = 0.332, p < 0.001). Parallel analysis showed that serum MCP-1 was also an independent predictor of carotid IMT incrassation, but this association was lost when serum OPG was included in the model. CONCLUSION: Serum OPG levels were increased and correlated with serum MCP-1 levels in premenopausal SLE patients. Increased serum OPG was independently associated with subclinical atherosclerosis in these patients.

Oral immunization of fish against iridovirus infection using recombinant antigen produced from rice callus.

Fish iridoviruses cause systemic diseases with high morbidity and mortality in various species of wild and farm-raised fish, resulting in severe economic losses, and no large-scale protective vaccine program or therapy is currently available. In this study, we expressed a recombinant major capsid protein (rMCP) of rock bream iridovirus in transgenic rice callus. The rMCP in lyophilized rice callus powder was added to feed to induce intestinal mucosal immunity for protection against and/or to reduce the severity of the iridovirus infection. We found that fish (Rock bream) immunized orally with rMCP underwent successful induction of antibodies (P<0.05) and were protected (P<0.001) against viral challenge. These results suggest that oral administration of rMCP as an antigen is a useful method to implement a vaccine program against iridovirus and other marine viral diseases.

Effects of various plasticizers and nanoclays on the mechanical properties of red algae film.

UNLABELLED: To manufacture red algae (RA) film, we used various plasticizers such as glycerol, sorbitol, sucrose, fructose, and polypropylene glycol (PPG), and then determined the mechanical properties of the RA films. The tensile strength (TS), elongation at break (E), and water vapor permeability (WVP) of the films containing various plasticizers ranged between 0.43 to 9.10 MPa, 10.93% to 47.17%, and 1.28 to 1.42 ng m/m2sPa, respectively. RA films containing fructose as a plasticizer had the best mechanical properties of all the films evaluated. Incorporation of nanoclay (Cloisite Na+ and 30B) improved the mechanical properties of the films. RA film with 3% Cloisite Na+ had a TS of 10.89, while RA film with 30B had a TS of 10.85 MPa; these films also had better E and WVP values than the other RA films evaluated. These results suggest that RA/nanoclay composite films are suitable for use as food packaging materials. PRACTICAL APPLICATION: Edible RE/nanoclay composite films prepared in the present investigation can be applied in food packaging.

Mid-life and late-life vascular risk factors and dementia in Korean men and women.

Dementia is one of the most important neurological disorders in the elderly population. The significance of vascular risk factors for dementia remains controversial. This study aimed to determine the effects of vascular risk factors, such as blood pressure, diabetes and smoking in the mid-life or the late-life on dementia risk. The data in this prospective cohort study came from 3252 dementia events occurring over 14 years among 848,505 Koreans aged 40-95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation during 1992-1995. Data on clinical dementia during the period 1993-2006 were examined in relation to vascular risk factors. The age adjusted incidence per 100,000 was 31.9 for men and 45.0 for women, respectively. In multivariate Cox proportional hazard models, diabetes increased the risk of either dementia in Alzheimer's disease or vascular dementia in men and women, controlling for age, hypertension, total cholesterol, alcohol drinking, and smoking. Hypertension also increased vascular dementia in both men [Hazard ratio (HR)=2.6, 95% confidence interval (CI)=1.7-3.8] and women (HR=2.3, 95%CI=1.6-3.3). The association of hypertension or diabetes on risk of vascular dementia, however, among the group aged older than 65 was attenuated but remained as significant in men. There was no interaction between hypertension and diabetes on the risk of dementia. This study demonstrates that diabetes and hypertension increased the risk of vascular dementia. Treatment for these risk factors may reduce the risk of vascular dementia.

Quality of life and psychological adaptation of Korean adolescents with vitiligo.

AIM: The aim of the study was to evaluate the impact of vitiligo on the quality of life and psychological adaptation in a Korean adolescent population. METHODS: Fifty-seven adolescents aged 12 to 18 years with vitiligo were evaluated using self-report scales, namely the Skindex-29, Piers-Harris self-concept, Center for Epidemiologic Studies Depression Scale (CES-D), and Revised Children's Manifest Anxiety Scale (RCMAS). RESULTS: Mean Skindex-29 subscales were as follow; 21.8 (global), 16.3 (symptom), 18.6 (function) and 29.5 (emotion). Several clinical variables, such as duration of vitiligo, facial involvement, history of previous treatment, and patient-assessed severity, affected the Skindex-29 subscales in various ways. However, differences in Skindex-29 scores according to the type of vitiligo, extent of involvement, and family history were not observed. The Piers-Harris self-concept scores showed a negative correlation with Skindex-29 scores, while other psychological measures (CES-D and RCMAS) were positively correlated. CONCLUSION: The quality of life of adolescents with vitiligo is closely related to the patients' apprehensions about their disease, psychosocial adjustment, and psychiatric morbidity, rather than the clinical severity of the condition itself. Clinicians should recognize and deal with psychological adaptation along with medical intervention when treating adolescent patients with vitiligo.

Comprehensive clinical follow-up of late effects in childhood cancer survivors shows the need for early and well-timed intervention.

BACKGROUND: Due to recent advances in treatment, nearly 80% of childhood cancer patients become long-term survivors. Studies on the late effects of survivors are under way worldwide. However, data on Asian survivors remain limited. METHODS: Data on 241 survivors at the Long-term Follow-up Clinic in Severance Hospital, South Korea, were collected and late effects were confirmed by oncologists. RESULTS: The median follow-up from diagnosis was 7.8 years. Late effects were identified in 59.8% of survivors and 23.2% had two or more late effects. Grade 3 or higher late effects were present in 10.8%. The most common late effects involved endocrine system (29.0%). Late effects were present in 95.7% of brain tumor survivors and 36.0% of Wilms' tumor survivors. Chemotherapy, hematopoietic stem-cell transplantation and radiotherapy were significant factors associated with the number and severity of late effects (P < 0.05). Brain tumor survivors had more severe late effects (P < 0.001), whereas Wilms' tumor survivors had fewer and milder late effects (P < 0.05). CONCLUSION: The observation that over 50% of cancer survivors suffered from late effects during the short follow-up period and that a high frequency of endocrine late effects was present indicates the need for early and well-timed intervention of the survivors.

Circulating osteoprotegerin levels are elevated and correlated with antiphospholipid antibodies in patients with systemic lupus erythematosus.

Patients with antiphospholipid syndrome (APS) have an increased risk for the development of thrombotic complications. Recent studies indicate that osteoprotegerin (OPG) acts as an important molecule in the development of vascular diseases. The aim of the present study was to examine the association between serum OPG levels and APS manifestations in patients with SLE. Seventy-nine patients with SLE and ninety-two healthy controls, matched for age and sex, were included in this study. Serum levels of OPG, monocyte chemoattractant protein(MCP)-1 and soluble E-selectin were determined by ELISA. At the time of serum sampling, various clinical and laboratory parameters were assessed. We found that serum levels of OPG were significantly higher in patients with SLE than in healthy controls (1236 +/- 82 vs 967 +/- 37 pg/mL, P = 0.003). Particularly, serum OPG levels were significantly higher in SLE patients with APS than those without (1615 +/- 191 vs 1171 +/- 91 pg/mL, P = 0.006). Serum OPG levels correlated with titres of IgG anti-cardiolipin antibody (P = 0.026) and anti-beta(2)-glycoprotein I antibody (P < 0.001). Moreover, serum OPG also correlated with serum levels of sE-selectin (P = 0.002), which is an endothelial cell activation marker, and MCP-1 (P = 0.003), a well known chemokine implicated in thrombogenesis. Collectively, serum OPG levels were increased in SLE patients with APS and correlated with titres of antiphospholipid antibodies, suggesting that OPG might be linked to the development of APS.

Fabrication of transparent capacitive structure by self-assembled thin films.

An approach to fabricating transparent electronic devices by using nanomaterial and nanofabrication is presented in this paper. A see-through capacitor is constructed from self-assembled silica nanoparticle layers that are stacked on the transparent substrate. The electrodes are made of indium tin oxide. Unlike the traditional processes used to fabricate such devices, the self-assembly approach enables one to synthesize the thin film layers at lower temperature and cost, and with a broader availability of nanomaterials. The vertical dimension of the self-assembled thin films can be precisely controlled, as well as the molecular order in the thin film layers. The shape of the capacitor is generated by planar micropatterning. The monitoring by quartz crystal demonstrates the steady growth of the silica nanoparticle multilayer. In addition, because the material synthesis and the device fabrication steps are separate, the fabrication is not affected by the harsh conditions required for the material synthesis. As a result, a clear pattern is allowed over a large area on the substrate. The prepared capacitive structure has an optical transparency higher than 92% over the visible spectrum. The capacitive impedance is measured at different frequencies and fit the theoretical results. As one of the fundamental components, this type of capacitive structure can serve in the transparent circuits, interactive media and sensors, as well as being applicable to other transparent devices.