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o,p '-Dichlorodiphenyltrichloroethane ( o,p '-DDT) is a representative endocrine disruptor, and exposure to o,p '-DDT may produce immune disorders and inflammation, leading to various diseases such as cancer. Chronic airway inflammation is characterized by excessive mucus secretion resulting in chronic obstructive pulmonary disease (COPD). Mucin 5AC  (MUC5AC), one of the mucus genes, plays an important role in mucus secretion and inflammation in the airways. The aim of this study was to examine the effects of o,p '-DDT on the regulation of MUC5AC expression in human lung epithelial A549 cell line. o,p '-DDT increased mRNA levels and the promoter activity of MUC5AC. Transient transfection with mutation promoter constructs of MUC5AC demonstrated that nuclear factor kappa-b (NF-κB) and activator protein 1(AP-1) response elements were essential for the consequences of o,p' -DDT on MUC5AC expression. In addition, o,p '-DDT induced phosphorylation of ERK, JNK, p38, and Akt, which are involved in the regulation of MUC5AC expression. It is noteworthy that inhibitors of NF-κB, AP-1, Akt, and MAPKs blocked enhanced o,p '-DDT-induced MUC5AC mRNA expression. Data indicate that o,p '-DDT increase in NF-κB, and AP-1 transcriptional activation-dependent MUC5AC expression is associated with stimulation of Akt and MAPK signaling pathways in A549 cells.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts., Competing Interests: The authors have declared that no competing interests exist.

G protein-coupled estrogen receptor (GPER) is important for maintaining normal blood vessel function by preventing endothelial cell dysfunction. It has been reported that G-1, an agonist of GPER, increases nitric oxide (NO) production through the phosphorylation of endothelial nitric oxide synthase (eNOS). However, the effect of GPER activation on eNOS expression has not been studied. Our results show that G-1 significantly increased the expression of eNOS and Kruppel-like factor 2 (KLF2) in human endothelial EA.hy926 cells. The individual silences of KLF2 and GPER attenuated G-1-induced eNOS expression. In addition, inhibition of the Gαq and Gβγ suppressed G-1-induced the expression of eNOS and KLF2 in EA.hy926 cells. Interestingly, these effects were similar in HUVECs. Furthermore, we found that GPER-mediated Ca 2+ signaling increased the phosphorylation of CaMKKβ, AMPK, and CaMKIIα in the cells. The phosphorylation of histone deacetylase 5 (HDAC5) by activation of AMPK and CaMKIIα increased the expression of eNOS via transcriptional activity of KLF2. We further demonstrate that GPER activation increased the phosphorylation of Src, EGFR, ERK5, and MEF2C and consequently induced the expression of eNOS and KLF2. Meanwhile, inhibition of ERK5 and HDAC5 suppressed the expression of eNOS and KLF2 induced by G-1 in the cells. These findings suggest that GPER provides a novel mechanism for understanding the regulation of eNOS expression and is an essential therapeutic target in preventing cardiovascular-related endothelial dysfunction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

CD63, a member of the tetraspanin family, is involved in the activation of immune cells, antiviral immunity, and signal transduction. The economically important anemonefishes Amphiprion sp. often face disease outbreaks, and the present study aimed to characterize CD63 in Amphiprion clarkii (denoted AcCD63) to enable better disease management. The in-silico analysis revealed that the AcCD63 transcript is 723 bp long and encodes 240 amino acids. The 26.2 kDa protein has a theoretical isoelectric point of 5.51. Similar to other tetraspanins, AcCD63 consists of four domains: short N-/C-terminal domains and small/large extracellular loops. Pairwise sequence alignment revealed that AcCD63 has the highest identity (100%) and similarity (99.2%) with CD63 from Amphiprion ocellaris. Multiple sequence alignment identified a conserved tetraspanin CCG motif, PXSCC motif, and C-terminal lysosome-targeting GYEVM motif. The quantitative polymerase chain reaction analysis showed that AcCD63 was highly expressed in the spleen and head kidney tissue, with low levels of expression in the liver. Temporal expression patterns of AcCD63 were measured in the head kidney and blood tissue after injection of polyinosinic:polycytidylic acid (poly (I:C)), lipolysacharides (LPS), or Vibrio harveyi (V. harveyi). AcCD63 was upregulated at 12 h post-injection with poly (I:C) or V. harveyi, and at 24 h post-injection with all stimulants in the head kidney. At 24 h post-injection, poly (I:C) and LPS upregulated, whereas V. harveyi downregulated AcCD63 expression in the blood. All viral hemorrhagic septicemia virus transcripts (M, G, N, RdRp, P, and NV) were downregulated in response to AcCD63 overexpression, and removal of viral particles occurred via the involvement of AcCD63. The expression of antiviral genes MX dynamin-like GTPase 1, interferon regulatory factor 3, interferon-stimulated gene 15, interferon-gamma, and viperin in CD63-overexpressing fathead minnow cells was downregulated. Collectively, our findings suggest that AcCD63 is an immunologically important gene involved in the A. clarkii pathogen stress response., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objectives : This study sought to investigate the natural course, the chronicity and recurrence rate, and the risk factors of chronic and recurrent herpes zoster ophthalmicus (HZO). We also evaluated the effects of long-term treatment for HZO. Materials and Methods : Patients diagnosed and treated for HZO were included in the retrospective medical chart review. Multivariable-adjusted logistic and Cox regression models were used to show risk factors for chronic and recurrent HZO along with hazard ratios (HRs) and 95% confidence intervals (CIs). Results : Among a total 130 of HZO patients, 31 patients (23.85%) had chronic disease and 19 patients (14.62%) had recurrent disease. The rate of chronic disease was higher in HZO with conjunctivitis, epithelial keratitis, and stromal keratitis. The recurrence rate increased in patients with chronic HZO (HR: 34.4, 95% CI: 3.6-324.6), epithelial keratitis (HR: 5.5, 95% CI: 1.3-30.0), stromal keratitis (HR: 18.8, 95% CI: 3.0-120.8), and increased intraocular pressure (IOP) (HR: 7.3, 95% CI: 1.6-33.2). Length of systemic antiviral therapy and anti-inflammatory eyedrop treatment were not associated with recurrent HZO ( p = 0.847 and p = 0.660, respectively). The most common ocular manifestation for recurrent HZO was stromal keratitis. Conclusions : This study demonstrated a considerable frequency of chronic and recurrent HZO. Chronic HZO in the form of epithelial or stromal keratitis with increased IOP provoked a significant rise in the risk of recurrence.

Purpose: To evaluate monocular and binocular visual performance and patient-reported outcomes following combined implantation of a diffractive extended depth of focus (EDoF) IOL (Carl Zeiss AT LARA 829MP) and a diffractive trifocal IOL (Carl Zeiss AT LISA tri 839MP)., Methods: This prospective study enrolled consecutive patients undergoing lens phacoemulsification of cataract and combined implantation of an EDoF IOL in the dominant eye and a trifocal IOL in the nondominant eye. Assessment included uncorrected visual acuity at near distances (UNVA), intermediate distances (UIVA), and far distances (UDVA), uncorrected defocus curve, contrast sensitivity (CS), reading speed, and patient satisfaction, evaluated six months after the surgery with the Visual Function Questionnaire (VFQ-25)., Results: A total of 25 patients were enrolled. At six months postoperatively, outcomes of binocular UNVA, UIVA, and UDVA were superior to those of monocular outcomes. The binocular defocus curve showed significantly better results in comparison with the AT LISA tri IOL eyes at defocus levels of -1.0 D and -1.5 D ( P =0.008 and P =0.002, respectively) and compared to the AT LARA IOL eyes at defocus levels of -3.0, -3.5 D, and -4.0 D ( P =0.019, P =0.019, and P =0.035, respectively). All of the patients were spectacle-free at far and intermediate distances, while 4% of patients needed spectacles at the near distance. Reading speed showed a rather high and gentle slope curve between 0.1 logMAR and 0.4 logMAR, and optical phenomena were improved after combined implantation of IOLs except halos. There were no significant differences in CS between the binocular and monocular results of each IOL., Conclusions: The combined implantation of an EDoF IOL and a trifocal IOL seems to be a good option for patients with demands for spectacle independence in their daily life, with minimal photic phenomena., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ji Eun Song et al.)

Purpose: To analyse and compare the propensity to form glistenings in 4 different types of hydrophobic acrylic intraocular lenses (IOLs): Alcon AcrySof ® MA60AC, HOYA iSert® PC-60AD, Bausch&Lomb enVista, and Kowa Avansee™ PU6A., Methods: We used an accelerated laboratory method to create glistenings. IOLs were first immersed in saline at 45 °C for 24 h and then at 37 °C for 2.5 h. Microvacuole (MV) density and size were documented and calculated using an image analysis program., Results: Median density of glistenings [MV/mm 2 ] for Alcon AcrySof ® MA60AC was 623 (range 507-804), for HOYA iSert® PC-60AD 1358 (range 684-2699), for Bausch&Lomb enVista 2 (range 1-2), and for Kowa Avansee™ PU6A 1 (range 1-4). The prevailing MV size was: 0-5 µm for Hoya IOLs, 5-10 µm for Alcon IOLs, 20-50 µm for Bausch&Lomb IOLs, and 5-50 µm for Kowa IOLs., Conclusions: Glistenings could be induced in all studied IOLs using the accelerated laboratory method. The Alcon AcrySof ® MA60AC and HOYA iSert® PC-60AD IOLs showed MV of high density, while the glistenings in the Hoya IOLs were smaller in size compared to the Alcon IOLs. The MV density was minimal in the Bausch&Lomb enVista and Kowa Avansee™ PU6A IOLs. The propensity of the Alcon AcrySof ® MA60AC IOLs to form glistenings in vitro correlated with the findings of clinical results that are already published., (© 2021. The Author(s).)

We investigated longitudinal changes in the spherical equivalent refractive error (SE) in hyperopic children with or without refractive accommodative esotropia (AccET). A total of 456 patients met the inclusion criteria: 190 (41.7%) in the hyperopic control group and 266 (58.3%) in the AccET group. All patients received at least 3 years of follow-up after spectacle prescription. Subgroups were divided according to age when spectacles were prescribed, presence of amblyopia, or initial SE. Longitudinal changes in SE in children with hyperopia showed a gradual decrease, although SE of younger children with AccET increased over the first 4 years and then decreased thereafter. SE in eye with higher SE was tended to decrease significantly in patient with Acc ET than hyperopic control group (group × time p = 0.015). Amblyopic eyes showed a greater decreased in SE compared with non-amblyopic eyes, but it was not statistically significant ( p = 0.07). SE was significantly decreased in children with more hyperopia (≥ 3 D) compared with children with less hyperopia (<3 D) ( p = 0.008). Emmetropization of hyperopia was faster in hyperopic patients without AccET and could be affected by the age of the initial spectacles prescription, initial amount of SE, or presence of amblyopia.

Background: Qualitative visualization of forward light scatter and quantitative straylight measurement of intraocular lenses (IOLs)., Methods: We analyzed two calcified IOL-explants, the Euromaxx ALI313Y (Argonoptics GmbH) and the LS-312 MF30 (Oculentis BV), one IOL with artificially induced glistenings (PC-60AD, Hoya), and one control (CT Asphina 409MP, Carl Zeiss Meditec AG) free of any opacification. Analysis included light microscopy, qualitative light scatter visualization using ray propagation imaging technique, and quantitative straylight measurement using C-Quant (Oculus)., Results: More light scattering effect-visible as increased light intensity outside the IOL's main focus-was evident in all opacified IOLs than the control. The highest straylight levels were observed in the Euromaxx (289.71 deg 2 /sr), which showed extensive granular deposits throughout its optic, followed by the MF30 (78.58 deg 2 /sr), which only showed opacification in its center. The glistenings-IOL demonstrated numerous microvacuoles within the optic and had straylight levels of 22.6 deg 2 /sr, while the control showed the lowest straylight levels (1.7 deg 2 /sr)., Conclusions: Ray propagation imaging technique allowed qualitative assessment of off-axis veils of light that result from increased forward light scattering. Straylight was increased in all opacified lenses compared to the clear control lens. The IOL opacifications are significant sources of glare.

The endangered Black-faced Spoonbill (Platalea minor) strictly breeds in marine environments and is threatened by the rapid loss of coastal wetlands within its breeding range. Adults with chicks are thought to gradually switch feeding sites from freshwater wetlands to coastal mudflats as the chicks' osmoregulatory system develops. We investigated age-dependent shifts in the diet of Black-faced Spoonbill chicks at four breeding colonies with varying freshwater habitat availability by examining stable isotopes (δ13C, δ15N) between the tip (grown at the age of 10 days) and middle (grown at the age of 22 days) portions of their primary feathers. The δ13C value of the middle portions was significantly higher than that of the tips, which suggested that the ratio of marine resources increased with the growth and development of chicks. A Bayesian isotope mixing model revealed that the diet proportion of marine prey in the early-chick rearing season was slightly higher than in the late-chick rearing season at three colonies in inshore areas, although this proportion was approximately 60% even in the early chick-rearing period. In contrast, isotopic values and reconstructed diet composition suggested that chicks in an offshore colony with limited freshwater wetlands relied more heavily on freshwater diets for both chick-rearing periods (>80%). Our results suggest that the shifts in feeding sites seen in previous studies might be related to the age-dependent dietary shift of chicks, highlighting the importance of freshwater wetlands for spoonbills on offshore islands without an inflow of freshwater in nearby intertidal mudflats. These findings emphasize the importance of freshwater prey and wetlands even for the endangered marine-breeding spoonbills, even though the negative impact of salt stress remains inconclusive., Competing Interests: The authors have declared that no competing interests exist.

Samples from 29 adult Gentoo (Pygoscelis papua), Chinstrap (Pygoscelis antarcticus), and Adélie Penguins (Pygoscelis adeliae) at the King Sejong Station on Nar̢ ebski Point, King George Island, Antarctica, were investigated to detect antibodies to avian influenza, Newcastle disease virus, infectious bursal disease virus, infectious bronchitis virus, Mycoplasma, and Salmonella. Antibodies were identified from one Gentoo Penguin and one Chinstrap Penguin against infectious bronchitis virus; from one Gentoo Penguin against Newcastle disease virus; from one Gentoo Penguin against Mycoplasma synoviae; and from two Chinstrap Penguins against Salmonella pullorum. Thirty-three dead penguin chicks were collected from the breeding colony for necropsy, histopathological examination, and polymerase chain reaction. Pulmonary hemorrhage and congestion were the main necropsy findings., (© Wildlife Disease Association 2021.)

Background: The longevity of polydioxanone (PDO)-barbed lifting threads remains controversial., Objectives: The authors sought to assess the longevity extension effect of a crisscross implantation pattern in PDO-barbed thread lifting., Methods: To acquire the desired outcome in PDO-barbed thread lifting, the authors suggested a paradigm shift to incorporate biochemical factors in enforcing the physico-mechanical lift. A nude mouse model was employed to evaluate their theory to compare the conventional fan-shaped protocols in barbed thread lifting with an architectural construction of intersections of fibrous capsule in a crisscross pattern. Three fragments of monofilament PDO-barbed-lifting threads were implanted in the dorsal skin of 12 nude mice. The pattern of implantation was fan-shaped in the control group and crisscross in the experimental group. Tissue specimens containing tangential areas of threads were harvested, fixed, and paraffin-embedded. Samples were horizontally cut and histologically analyzed employing hematoxylin and eosin, Massons' Trichrome, and Sirius red staining. Fibrotic areas and the width of fibrosis from the thread were also analyzed., Results: Fibrous capsulations around the barbed area of the PDO-barbed lifting threads were threefold greater than those around the barb-free areas of the threads. In the crisscross implantation pattern, width and density of the fibrotic areas were fivefold greater than those of the fan-shaped areas. Induction of fibrous capsules around the PDO-barbed thread was markedly condensed in the crisscross areas., Conclusions: This study provides the basis for a more logical implantation pattern in PDO-barbed lifting threads for facial rejuvenation. By generating controlled multiple crisscross patterns, we can create more intense fibrogenesis, reduce tension applied on each barbed thread, and, therefore, extend the longevity of the result., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Due to the limited supply of vessels and nerves, acute or chronic tendon injuries often result in significant and persistent complications, such as pain and sprains, as well as the loss of joint functions. Among these complications, tendon adhesions within the surrounding soft tissue have been shown to significantly impair the range of motion. In this study, to elucidate the effects of a hyaluronic acid (HA) injection at the site of tenorrhaphy on tendon adhesion formation, we used a full transection model of a rat's Achilles tendon to investigate the anti-adhesive function of HA. Our initial findings showed that significantly lower adhesion scores were observed in the HA-treated experimental group than in the normal saline-treated control group, as determined by macroscopic and histological evaluations. Hematoxylin and eosin, as well as picrosirius red staining, showed denser and irregular collagen fibers, with the larger number of infiltrating inflammatory cells in the control group indicating severe adhesion formation. Furthermore, we observed that the expression of tendon adhesion markers in operated tendon tissue, such as collagen type I, transforming growth factor-β1, and plasminogen activator inhibitor-1, was suppressed at both the gene and protein levels following HA treatment. These results suggest that HA injections could reduce tendon adhesion formation by significantly ameliorating inflammatory-associated reactions.

Background: Glistenings describe small, refractile microvacuoles that may arise within the intraocular lens (IOL) material and reduce the patients' quality of vision. Lenses composed of hydrophobic acrylic material are particularly affected by glistening formation. In this study, we compared the tendency of glistening formation in six different types of hydrophobic acrylic intraocular lenses (IOLs)., Methods: We used a well-established accelerated laboratory method to develop glistenings in the following IOLs: Vivinex XY1 (Hoya), AcrySof SN60WF (Alcon), Tecnis ZCB00 (AMO), Avansee PN6A (Kowa), Aktis SP NS-60YG (Nidek), and CT Lucia 601P (Zeiss). IOLs were first immersed in saline at 45 °C for 24 h and then at 37 °C for 2.5 h in a water bath. Microvacuole (MV) density and size (Miyata grading) were documented and calculated using an image analysis program., Results: The mean glistening density [MV/mm 2 ] and mean Miyata grading (in brackets) were: Vivinex: 11.6 ± 5.7 (0), SN60WF: 264.4 ± 110.3 (2.6), Tecnis: 6.0 ± 2.8 (0), Avansee: 2.2 ± 0.7 (0), Aktis: 851.4 ± 59.4 (3+) and CT Lucia: 71.0 ± 71.6 (1)., Conclusions: While all tested IOLs showed glistenings with the accelerated laboratory method, the Aktis and SN60WF showed the highest microvacuole density, followed by the CT Lucia. In comparison, the Vivinex, Tecnis, and Avansee IOLs showed far fewer number of glistenings.

Abstract: Scars are significant complications of wound healing and associated with negative physical, psychological, and cosmetic effects. Scar revision and laser treatment have been used over the past century to improve many different types of scars. Here, we evaluated the effectiveness of early combined carbon dioxide ablative fractional laser (AFL) and pulsed dye laser (PDL) treatment after scar revision. Fourteen patients who underwent scar revision were enrolled. All patients were treated with both a 10,600-nm AFL and a 595-nm PDL commencing 2 weeks after scar revision and continuing at 4-week intervals for a total of 4 treatments. Vancouver Scar Scale scores were evaluated before treatment and 5 months after the final treatment. All Vancouver Scar Scale scores improved significantly except that of scar height. We encountered no adverse complications (wound disruption, or hyper- or hypopigmentation) during follow-up. Early combined carbon dioxide AFL and PDL treatment after scar revision effectively and safely minimized scar formation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Abstract: In unilateral cleft lip and palate patients, the alar base is displaced inferoposterolaterally due to the depression of the pyriform aperture in the cleft side, and the drooping of the nostril rim is provoked by displacement of the alar base. This study was conducted between May 1998 and December 2012. In total, 82 patients with secondary unilateral cleft lip nasal deformities were treated using alar base augmentation. The patients were divided into two groups according to the degree of their preoperative alar base asymmetry. Patients with alar base asymmetry <3 mm were treated with a soft tissue augmentation procedure. Those with alar base asymmetry >3 and <6 mm were treated with a bony augmentation procedure. Soft tissue augmentation was conducted in 42 patients, and bony augmentation was conducted in 40 patients. In the soft tissue augmentation group, the degree of alar base asymmetry was improved from 2.42 ± 0.38 mm preoperatively to 0.45 ± 0.21 mm postoperatively (P  < 0.05). In the bony augmentation group, the degree of alar base asymmetry was improved from 4.33 ± 0.50 mm preoperatively to 0.81 ± 0.20 mm postoperatively (P  < 0.05). In the amount of alar base augmentation, there were statistically significant differences between the soft tissue augmentation group and the bony augmentation group (P  < 0.05). This clinical study shows that secondary cleft lip nasal deformities can be corrected with alar base augmentation using soft tissue and bony augmentation and that these procedures can provide reliable, satisfactory, and safe clinical outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Two genes encoding probable α-L-arabinofuranosidase (E.C. 3.2.1.55) isozymes (ABFs) with 92.3% amino acid sequence identity, ABF51A and ABF51B , were found from chromosomes 3 and 5 of Saccharomycopsis fibuligera KJJ81, an amylolytic yeast isolated from Korean wheat-based nuruk, respectively. Each open reading frame consists of 1,551 nucleotides and encodes a protein of 517 amino acids with the molecular mass of approximately 59 kDa. These isozymes share approximately 49% amino acid sequence identity with eukaryotic ABFs from filamentous fungi. The corresponding genes were cloned, functionally expressed, and purified from Escherichia coli . SfABF51 A and SfABF51 B showed the highest activities on p -nitrophenyl arabinofuranoside at 40~45°C and pH 7.0 in sodium phosphate buffer and at 50°C and pH 6.0 in sodium acetate buffer, respectively. These exo -acting enzymes belonging to the glycoside hydrolase (GH) family 51 could hydrolyze arabinoxylo-oligosaccharides (AXOS) and arabino-oligosaccharides (AOS) to produce only L-arabinose, whereas they could hardly degrade any polymeric substrates including arabinans and arabinoxylans. The detailed product analyses revealed that both SfABF51 isozymes can catalyze the versatile hydrolysis of α-(1,2)-and α-(1,3)-L-arabinofuranosidic linkages of AXOS, and α-(1,2)-, α-(1,3)-, and α-(1,5)-linkages of linear and branched AOS. On the contrary, they have much lower activity against the α-(1,2)-and α-(1,3)-double-substituted substrates than the single-substituted ones. These hydrolases could potentially play important roles in the degradation and utilization of hemicellulosic biomass by S. fibuligera .

Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.

Our recent paper ( https://doi.org/10.1186/s41073-020-00096-x ) reported that 43% of reviewer comment sets (n=1491) shared with authors contained at least one unprofessional comment or an incomplete, inaccurate of unsubstantiated critique (IIUC). Publication of this work sparked an online (i.e., Twitter, Instagram, Facebook, and Reddit) conversation surrounding professionalism in peer review. We collected and analyzed these social media comments as they offered real-time responses to our work and provided insight into the views held by commenters and potential peer-reviewers that would be difficult to quantify using existing empirical tools (96 comments from July 24th to September 3rd, 2020). Overall, 75% of comments were positive, of which 59% were supportive and 16% shared similar personal experiences. However, a subset of negative comments emerged (22% of comments were negative and 6% were an unsubstantiated critique of the methodology), that provided potential insight into the reasons underlying unprofessional comments were made during the peer-review process. These comments were classified into three main themes: (1) forced niceness will adversely impact the peer-review process and allow for publication of poor-quality science (5% of online comments); (2) dismissing comments as not offensive to another person because they were not deemed personally offensive to the reader (6%); and (3) authors brought unprofessional comments upon themselves as they submitted substandard work (5%). Here, we argue against these themes as justifications for directing unprofessional comments towards authors during the peer review process. We argue that it is possible to be both critical and professional, and that no author deserves to be the recipient of demeaning ad hominem attacks regardless of supposed provocation. Suggesting otherwise only serves to propagate a toxic culture within peer review. While we previously postulated that establishing a peer-reviewer code of conduct could help improve the peer-review system, we now posit that priority should be given to repairing the negative cultural zeitgeist that exists in peer-review.

China's coastal wetlands are critically important to shorebirds. Substantial loss of tidal flats, shorebirds' primary foraging grounds, has occurred from land claim and other processes, and is driving population declines in multiple species. Smooth cordgrass Spartina alterniflora was intentionally introduced to the coast of China in 1979 to promote conversion of tidal flats into dry land and has since spread rapidly. The occurrence of S. alterniflora reduces the availability of foraging and roosting habitat for shorebirds, and may be particularly detrimental in places that have experienced other tidal flat loss. However, the extent to which S. alterniflora is encroaching upon important shorebird habitat throughout coastal mainland China, and its intersection with tidal flat loss, has not been quantified. Here, we i) estimate change in the spatial extent of tidal flats between 2000 and 2015 in coastal mainland China where internationally important numbers of shorebirds have been recorded; ii) map the extent of S. alterniflora coverage in 2015 at the same set of sites; and, iii) investigate where these two threats to important shorebird habitat intersect. Our analysis of remote sensing data indicated a 15% net loss in tidal flat area between 2000 and 2015 across all sites, including a net loss in tidal flat area in 39 of 53 individual sites (74%). Spartina alterniflora occurred at 28 of 53 sites (53%) in 2015, of which 22 sites (79%) also had a net loss in tidal flat area between 2000 and 2015. Combined pressures from tidal flat loss and S. alterniflora invasion were most severe in eastern coastal China. Species highly dependent on migrating through this region, which include the Critically Endangered Spoon-billed Sandpiper and Endangered Nordmann's Greenshank and Far Eastern Curlew, may be particularly impacted. Our results underscore the urgent need to arrest tidal flat declines and develop a comprehensive control program for S. alterniflora in coastal areas of mainland China that are important for shorebirds., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The longitudinal relationship between smoking status and risk of developing visual impairment (VI) remains unclear. We examined the relationship of smoking status and urinary cotinine level, an objective measure of smoking, with incidence of VI. This cohort study included 279,069 individuals free of VI who were followed for up to 8.8 years (median 4.8 years). VI was defined as when bilateral visual acuity was worse than 0.5 (cutoffs of 0.3 Logarithm of the Minimum Angle of Resolution). During 1,324,429.8 person-years of follow-up, 7852 participants developed new-onset bilateral VI. Self-reported current smoking status was associated with increased risk of developing VI in both men and women, with a stronger association in women (P for interaction = 0.01). Multivariable adjusted hazard ratios (95% confidence intervals) for incident VI comparing current smokers to never-smokers were 1.14 (1.04-1.25) in men and 1.52 (1.28-1.80) in women. Urinary cotinine levels of ≥ 100 ng/ml were significantly associated with increased risk of incident VI, and these associations remained when introducing changes in urinary cotinine and other confounders during follow-up as time-varying covariates. Cigarette smoking assessed based on self-report and urinary cotinine level was associated with increased incidence of VI. Our findings identify smoking as an independent risk factor for VI.

Osteoporosis is a disease in which bone mineral density decreases due to abnormal activity of osteoclasts, and is commonly found in post-menopausal women who have decreased levels of female hormones. Sphingosylphosphorylcholine (SPC) is an important biological lipid that can be converted to sphingosine-1-phosphate (S1P) by autotaxin. S1P is known to be involved in osteoclast activation by stimulating osteoblasts, but bone regulation by SPC is not well understood. In this study, we found that SPC strongly inhibits RANKL-induced osteoclast differentiation. SPC-induced inhibitory effects on osteoclast differentiation were not affected by several antagonists of S1P receptors or pertussis toxin, suggesting cell surface receptor independency. However, SPC inhibited RANKL-induced calcineurin activation and subsequent NFATc1 activity, leading to decrease of the expression of Trap and Ctsk. Moreover, we found that bone loss in an experimental osteoporosis mouse model was recovered by SPC injection. SPC also blocked ovariectomy-induced body weight increase and Nfatc1 gene expression in mice. We also found that SPC inhibits RANKL-induced osteoclast differentiation in human macrophages. Since currently available treatments for osteoporosis, such as administration of female hormones or hormone receptor modulators, show serious side effects, SPC has potential as a new agent for osteoporosis treatment., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The extended distribution and potential introduction of exotic ticks and associated tick-borne pathogens along the northern and southern routes of migratory birds pose zoonotic tick-borne disease risks to wild and domestic animals and incidentally to humans. A knowledge of bird migratory patterns, species of attached ticks, and associated pathogens during their migrations to and from their feeding and nesting grounds is central to understanding associated tick-borne disease risks. Tick-borne disease surveillance was conducted from 2010 to 2011 and 2016 at Hong-do (do = island), Heuksan-do, and Nan-do, major stopovers for migratory birds in Republic of Korea (ROK), as part of the Migratory Birds Research Center bird-banding program for studying bird migration patterns in the ROK. A total of 877 ticks belonging to three genera and nine species were collected, Ixodes turdus (576, 65.7%), Haemaphysalis flava (134, 15.3%), H. longicornis (91, 10.4%), I. nipponensis (56, 6.4%), H. formosensis (7, 0.8%), H. ornithophila (6, 0.7%), H. phasiana (5, 0.6%), H. concinna (1, 0.1%), and Amblyomma testudinarium (1, 0.1%) were collected from 274 birds belonging to 20 genera and 41 species. A total of 15/380 pools (3.95%) were positive for Borrelia species (14 pools of I. turdus and 1 pool of H. flava ), while only 1/380 pools (0.26%) was positive for Anaplasma phagocytophilum (1 pool of I. nipponensis ). Our findings support the role of migratory birds as possible vectors for the introduction of tick-borne pathogens, which requires continuous monitoring for the potential introduction of ticks and their associated tick-borne pathogens.

Korean red pine needle (RPN) exhibits various biological and pharmacological activities. Among the various compounds of RPN, we isolated dehydroabietic and 4- epi - trans -communic acid. At first, we confirmed that two compounds inhibited angiotensin converting enzyme (ACE) and induced p-Akt in human umbilical vein endothelial cells (HUVEC). RPN extract powder significantly reduced systolic blood pressure in spontaneous hypertensive rats (SHRs) through the reduced expression of ACE and angiotensin type I receptors in the lungs of SHRs. The Lineweaver-Burk plots suggested that the two compounds were noncompetitive inhibitors of ACE. Using docking analysis, we found that two compounds showed the best returned pose at ACE active sites, and formed hydrogen and hydrophobic bonds with ACE residues. These results demonstrate that RPNs may be a source of compounds effective for preventing hypertension and may be useful in the development of antihypertensive drugs.

Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.

Regulatory T cells (Treg) are enriched in the tumor microenvironment (TME) and suppress antitumor immunity; however, the molecular mechanism underlying the accumulation of Tregs in the TME is poorly understood. In various tumor models, tumor-infiltrating Tregs were highly enriched in the TME and had significantly higher expression of immune checkpoint molecules. To characterize tumor-infiltrating Tregs, we performed bulk RNA sequencing (RNA-seq) and found that proliferation-related genes, immune suppression-related genes, and cytokine/chemokine receptor genes were upregulated in tumor-infiltrating Tregs compared with tumor-infiltrating CD4 + Foxp3 - conventional T cells or splenic Tregs from the same tumor-bearing mice. Single-cell RNA-seq and T-cell receptor sequencing also revealed active proliferation of tumor infiltrating Tregs by clonal expansion. One of these genes, ST2, an IL33 receptor, was identified as a potential factor driving Treg accumulation in the TME. Indeed, IL33-directed ST2 signaling induced the preferential proliferation of tumor-infiltrating Tregs and enhanced tumor progression, whereas genetic deletion of ST2 in Tregs limited their TME accumulation and delayed tumor growth. These data demonstrated the IL33/ST2 axis in Tregs as one of the critical pathways for the preferential accumulation of Tregs in the TME and suggests that the IL33/ST2 axis may be a potential therapeutic target for cancer immunotherapy., (©2020 American Association for Cancer Research.)

Several air pollution components such as sulfur dioxide, ozone, nitrogen dioxide, and diesel exhaust particulate matter (DEPM) have been linked to the development of asthma. In this study, we investigated the therapeutic potential of three lactic acid bacteria species, Lactobacillus plantarum GREEN CROSS Wellbeing (GCWB)1001, Pediococcus acidilactici GCWB1085, and Lactobacillus rhamnosus GCWB1156, in preventing DEPM-exacerbated asthma in mice. BALB/c mice were first sensitized with ovalbumin (OVA) and were either challenged with OVA or DEPM (DEPM-exacerbated asthma model) by intranasal instillation. All three strains showed no hemolytic activity, suggesting a good safety profile. Oral administration of lactic acid bacteria reduced OVA + DEPM-induced inflammatory infiltration, goblet cell hyperplasia, airway remodeling, and the levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF). The probiotics also attenuated OVA + DEPM-induced immunoglobulin E (IgE) levels in serum and in BALF, and significantly reduced caspase-3 activity, total collagen level, and matrix metalloproteinase (MMP)-9 activity. In conclusion, lactic acid bacteria such as L. plantarum GCWB1001, P. acidilactici GCWB1085, and L. rhamnosus treatment in mice with asthma showed significant efficacy in preventing lung inflammation exacerbated by DEPM administration.

Background: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine., Objective: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats., Design: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo . We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels., Results: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats., Conclusion: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future., Competing Interests: The authors declare that there no conflicts of interest. This work was supported by the Support Program for Creative Industry Institutes (Commercial Biotechnology Sophistication Platform Construction Program, R0003950) and Agenda program (Grant number 10067225), funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea)., (© 2020 Gyuok Lee et al.)

Marine microplastic pollution poses a threat to aquatic organisms, including bivalves. In this study, we investigated the accumulation of microplastics and their elicited antioxidant stress response in the bay scallop Argopecten irradians. Scallops were exposed to 1 μm diameter micro-polystyrene (MP) beads at 10, 100, and 1000 beads/mL concentrations for a 7 day period. Bead presence in the digestive diverticula and defense responses in the digestive diverticula and hemolymph were measured at 1, 3, 5, and 7 days. The activity and expression of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and H 2 O 2 in the digestive diverticula and/or hemolymph of scallops increased with microplastic concentration and exposure duration. These results suggest that microplastics can accumulate in the digestive diverticula of A. irradians, and that exposure to microplastics induces oxidative stress in bivalves. It is likely that exposure to high concentrations of micro- or nano-sized plastic particles could potentially have adverse effects in bivalves., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Interleukin 33 (IL-33) is an IL-1 family cytokine that plays a central role in immune system by regulating and initiating inflammatory responses. The binding of IL-33 to the suppressor of tumorigenicity 2 (ST2) receptor induces mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways, thereby leading to inflammatory cytokines production in type 2 helper T cells and type 2 innate lymphoid cells. To develop an antibody specific to IL-33 with a defined epitope, we characterized a single-chain antibody variable fragments (scFvs) clone specific to IL-33, C2&#95;2E12, which was selected from a human synthetic library of scFvs using phage display. Affinity ( K d ) of C2&#95;2E12 was determined to be 38 nM using enzyme-linked immunosorbent assay. C2&#95;2E12 did not show cross-reactivity toward other interleukin cytokines, including closely related IL-1 family cytokines and unrelated proteins. Mutational scanning analysis revealed that the epitope of IL-33 consisted of residues 149-158 with key residues being L150 and K151 of IL-33. Structural modeling suggested that L150 and K151 residues are important for the interaction of IL-33 with C2&#95;2E12, implicating that C2&#95;2E12 could block the binding of ST2 to IL-33. Pull-down and in-cell assays supported that C2&#95;2E12 can inhibit the IL-33/ST2 signaling axis. These results suggest that the scFv clone characterized here can function as a neutralizing antibody.

This study investigated the mechanical properties of steel in flanges, with the goal of obtaining high strength and high toughness. Quenching was applied alone or in combination with tempering at one of nine combinations of three temperatures T TEM and durations t TEM . Cooling rates at various flange locations during quenching were first estimated using finite element method simulation, and the three locations were selected for mechanical testing in terms of cooling rate. Microstructures of specimens were observed at each condition. Tensile test and hardness test were performed at room temperature, and a Charpy impact test was performed at -46 °C. All specimens had a multiphase microstructure composed of matrix and secondary phases, which decomposed under the various tempering conditions. Decrease in cooling rate (CR) during quenching caused reduction in hardness and strength but did not affect low-temperature toughness significantly. After tempering, hardness and strength were reduced and low-temperature toughness was increased. Microstructures and mechanical properties under the various tempering conditions and CRs during quenching were discussed. This work was based on the properties directly obtained from flanges under industrial processes and is thus expected to be useful for practical applications.

Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 75 ± 7% (mean ± SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 ± 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups.

Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP) and spike protein receptor binding domain (RBD). The seropositive cutoff value was set using a cohort of 294 anonymous serum specimens collected in 2018. The specificity was assessed using serum specimens collected from organ donors or influenza patients before 2020. Seropositive rate was determined among COVID-19 patients. Time-to-seropositivity and signal-to-cutoff (S/CO) ratio were compared between MBA and EIA. MBA had a specificity of 100% (93/93; 95% confidence interval (CI), 96-100%) for anti-NP IgG, 98.9% (92/93; 95% CI 94.2-100%) for anti-RBD IgG. The MBA seropositive rate for convalescent COVID-19 patients was 89.8% (35/39) for anti-NP IgG and 79.5% (31/39) for anti-RBD IgG. The time-to-seropositivity was shorter with MBA than EIA. MBA could better differentiate between COVID-19 patients and negative controls with higher S/CO ratio for COVID-19 patients, lower S/CO ratio with negative controls and fewer specimens in the equivocal range. MBA is robust, simple and is suitable for clinical microbiology laboratory for the accurate determination of anti-SARS-CoV-2 antibodies for diagnosis, serosurveillance, and vaccine trials.

The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus . However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms.

Background: A cruise ship is a closed-off environment that simulates the basic functioning of a city in terms of living conditions and interpersonal interactions. Thus, the Diamond Princess cruise ship, which was quarantined because of an onboard outbreak of COVID-19 in February, 2020, provides an opportunity to define the shedding pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient antibody responses before and after the onset of symptoms., Methods: We recruited adult (≥18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship docked in Yokohama, Japan in February, 2020. All participants had been found to be negative for SARS-CoV-2 by RT-PCR 4 days before disembarking and were transferred to further quarantine in a public estate in Hong Kong, where they were recruited. Participants were prospectively screened by quantitative RT-PCR (RT-qPCR) of nasopharyngeal and throat swabs, and serum IgG and IgM against internal nucleoprotein and the surface spike receptor-binding protein (RBD) of SARS-CoV-2 at baseline (upon entering quarantine) and on days 4, 8, and 12 of quarantine., Findings: On Feb 22, 2020, 215 adults were recruited, of whom nine (4%; 95% CI 2-8) were positive for SARS-CoV-2 by RT-qPCR or serology and were hospitalised. Of these nine patients, nasopharyngeal swab RT-qPCR was positive in eight patients (89%; 57-99) at baseline. All nine patients were positive for anti-RBD IgG by day 8. Eight (89%; 57-99) were simultaneously positive for nasopharyngeal swab RT-PCR and anti-RBD IgG. One patient who was positive for anti-RBD IgG and had a negative viral load had multifocal peripheral ground-glass changes on high-resolution CT that were typical of COVID-19. Five patients (56%; 27-81) with ground-glass changes on high-resolution CT were found to have higher anti-nucleoprotein-IgG OD values on day 8 and 12 and anti-RBD IgG OD value on day 12 than patients without ground-glass changes. Six (67%; 35-88) patients remained asymptomatic throughout the 14-day quarantine period., Interpretation: Patients with COVID-19 can develop asymptomatic lung infection with viral shedding and those with evidence of pneumonia on imaging tend to have an increased antibody response. Positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients. A combination of RT-PCR and serology should be implemented for case finding and contact tracing to facilitate early diagnosis, prompt isolation, and treatment., Funding: Shaw Foundation Hong Kong; Sanming-Project of Medicine (Shenzhen); High Level-Hospital Program (Guangdong Health Commission)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: Das IVCRC erhält Forschungsgelder von den Firmen Alcon, Oculus und Ophtec. G. Auffarth und R. Khoramnia erhalten Vortragshonorare sowie Reisekostenerstattungen von den Firmen Alcon, Oculus und Ophtec. D. Scharf, T. Yildirim, C. Choi und C. Mayer geben an, dass kein Interessenkonflikt besteht.

Recently, Lactococcus lactis subsp. lactis has been reported to have immunostimulating properties in an immunosuppressed-animal model. However, the immunological activities of Lactococcus lactis and the molecular mechanisms remain unclear. In this report, we evaluated the immunostimulating activity and associated mechanisms of Lactococcus lactis subsp. lactis GCWB1176 (GCWB1176) in macrophages and cyclophosphamide (CTX)-induced immunosuppressed mice. In a series of safety tests, GCWB1176 was found to have a negative response to hemolysis, as well as susceptibility to antibiotics. Administration of GCWB1176 elevated natural killer (NK) cell activities; concanavalin A-induced T cell proliferation; and serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10 and IL-12 in CTX-induced immunosuppressed mice. In RAW264.7 macrophages, treatment with GCWB1176 induced phagocytic activity and increased the production of nitric oxide (NO) and expression of inducible NO synthase. Simultaneously, GCWB1176 increased the production of TNF-α, IFN-γ, IL-1β, IL-10 and IL-12 from mouse splenocytes and RAW264.7 cells. In addition, GCWB1176 significantly increased the transcriptional activities of NF-κB and iNOS. Taken together, GCWB1176 improved immune function through the activation of macrophages and NK cells. These findings suggest that dietary supplementation of GCWB1176 may be used to enhance immunity.

In this study, we explored whether the use of Streptococcus thermophilus LM1012 (TL-LM1012) as a safe probiotic exerts hepatoprotective effects by suppressing oxidative stress and inflammation in vitro and alleviating aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) production in vivo . In a series of safety tests, TL-LM1012 was found to have a negative response to hemolysis and biogenic amines, as well as susceptibility to antibiotics. TL-LM1012 protected cell viability and suppressed cytotoxicity by inhibiting oxidative stress and induced heme oxygenase-1 and superoxide dismutase activity in a dose-dependent manner in diesel exhaust particulate matter (DEPM)-treated HepG2 cells. Moreover, proinflammatory cytokines, including tumor necrosis factor- α , interleukin (IL)-6, and IL-1 β , were suppressed in DEPM-treated splenocytes. In DEPM-treated mice, oral administration of TL-LM1012 regulated AST, ALT, and LDH production in the serum after 14 days of treatment. These findings indicate that TL-LM1012, a safe probiotic, provides a potent preventive or therapeutic effect against liver disease caused by air pollution.

Purpose: To compare the clinical outcomes of mix-and-match implantation of a diffractive extended depth of focus intraocular lens (IOL) (TECNIS Symfony ZXR00; Johnson & Johnson Vision) and a diffractive bifocal IOL (TECNIS ZLB00 +3.25 diopters [D]; Johnson & Johnson Vision) and bilateral implantation of a diffractive trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc)., Methods: This prospective comparative study compares the clinical outcomes of patients with age-related cataract undergoing cataract surgery using the IOLs described. Patients were divided into the mix-and-match group and the trifocal group. Assessment included monocular and binocular uncorrected distance visual acuity (UDVA), intermediate visual acuity (UIVA at 60 cm), and near visual acuity (UNVA at 40 cm), uncorrected defocus curves, contrast sensitivity, and reading speed. Quality of vision was measured with the Visual Function Questionnaire (VFQ-25)., Results: A total of 50 patients (25 in each group) were enrolled. At 6 months postoperatively, outcomes of binocular UDVA, UIVA, and UNVA were similar in both groups. The binocular defocus curve only differed at vergences of -0.50 to -1.00 D (better for the mix-and-match group; P = .032 and .004, respectively) and at -4.00 D (better for the trifocal group; P = .001). Significantly higher reading speeds in the mix-and-match group were measured at 0.7 and 0.5 logMAR (P = .038 and .034, respectively). There were no significant differences between groups for contrast sensitivity and the results of the questionnaire., Conclusions: The mix-and-match implantation seemed to be a good option for patients with high demands for distance and intermediate visual acuity, whereas the trifocal IOL appeared to be more suitable for patients with enhanced near vision demands. [J Refract Surg. 2020;36(8):528-535.]., (Copyright 2020, SLACK Incorporated.)

The world's biomes and their associated ecosystems are artificially fractured by geopolitical boundaries that define countries. Yet 'transboundary' landscapes often overlap with biodiversity hotspots, contain surprisingly important ecosystems, and provide critical habitats for threatened species. Notwithstanding, biodiversity in these landscapes is increasingly imperiled by infrastructure, including walls and fences along borders and cross-border roads that drive landscape fragmentation and the loss of ecological connectivity. Associated problems due to reduced governance (e.g., illegal wildlife trade) also undermine conservation efforts in these important regions. In this review, we distinguish positive and negative effects of transboundary frontiers on biodiversity conservation, discuss lessons from existing frameworks, and identify scenarios that can maximize opportunities for biodiversity conservation in transboundary frontiers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Vertebrate ancient long (VAL)-opsin is a green-sensitive photoreceptor that shows high sequence similarity to vertebrate ancient opsin, which is considered to play a role in sexual maturation via gonadotropin-releasing hormone (GnRH); however, the role of VAL-opsin in vertebrate sexual maturity remains unclear. Therefore, we investigated the possible role of VAL-opsin in reproduction in the goldfish Carassius auratus under a state of GnRH inhibition. Goldfish were injected with recombinant VAL-opsin protein (0.5 μg/g body mass) and/or the GnRH antagonist cetrorelix (0.5 μg/fish), and changes in the mRNA expression levels of genes associated with goldfish reproduction were measured by quantitative polymerase chain reaction, including those involved in the hypothalamus-pituitary-gonad (HPG) axis, VAL-opsin, GnRH, the gonadotropins (GTHs) luteinizing hormone and follicle-stimulating hormone, and estrogen receptor (ER). Moreover, the fish were irradiated with a green light-emitting diode (520 nm) to observe the synergistic effect on the HPG axis with VAL-opsin. Green LED exposure significantly and slightly increased the VAL-opsin and GnRH levels, respectively; however, these effects were blocked in groups injected with cetrorelix at all time points. Cetrorelix significantly decreased the mRNA levels of GTHs and ER, whereas these hormones recovered by co-treatment with VAL-opsin. These results indicate that green LED is an effective light source to promote the expression of sex hormones in fish. Moreover, VAL-opsin not only affects activity of the HPG axis but also appears to act on the pituitary gland directly to stimulate a new sexual maturation pathway that promotes the secretion of GTHs independent of GnRH.

Stress granules are membraneless organelles composed of numerous components including ribonucleoproteins. The stress granules are characterized by a dynamic complex assembly in response to various environmental stressors, which has been implicated in the coordinated regulation of diverse biological pathways, to exert a protective role against stress-induced cell death. Here, we show that stress granule formation is induced by morusin, a novel phytochemical displaying antitumor capacity through barely known mechanisms. Morusin-mediated induction of stress granules requires activation of protein kinase R (PKR) and subsequent eIF2α phosphorylation. Notably, genetic inactivation of stress granule formation mediated by G3BP1 knockout sensitized cancer cells to morusin treatment. This protective function against morusin-mediated cell death can be attributed at least in part to the sequestration of receptors for activated C kinase-1 (RACK1) within the stress granules, which reduces caspase-3 activation. Collectively, our study provides biochemical evidence for the role of stress granules in suppressing the antitumor capacity of morusin, proposing that morusin treatment, together with pharmacological inhibition of stress granules, could be an efficient strategy for targeting cancer.

The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The process of peer-review in academia has attracted criticism surrounding issues of bias, fairness, and professionalism; however, frequency of occurrence of such comments is unknown., Methods: We evaluated 1491 sets of reviewer comments from the fields of "Ecology and Evolution" and "Behavioural Medicine," of which 920 were retrieved from the online review repository Publons and 571 were obtained from six early career investigators. Comment sets were coded for the occurrence of "unprofessional comments" and "incomplete, inaccurate or unsubstantiated critiques" using an a-prior rubric based on our published research. Results are presented as absolute numbers and percentages., Results: Overall, 12% (179) of comment sets included at least one unprofessional comment towards the author or their work, and 41% (611) contained incomplete, inaccurate of unsubstantiated critiques (IIUC)., Conclusions: The large number of unprofessional comments, and IIUCs observed could heighten psychological distress among investigators, particularly those at an early stage in their career. We suggest that development and adherence to a universally agreed upon reviewer code of conduct is necessary to improve the quality and professional experience of peer review., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: A larger optical zone for photorefractive keratectomy may improve optical quality and stability. However, there is need for limiting ablation diameter in that a larger ablation diameter requires greater ablation depth, and minimizing ablation depth may reduce adverse effects on postoperative wound healing, haze and keratoectasia. In this study, we compared the changes in clinical outcomes and the degree of regression between a 6.0 mm optical zone and 6.5 mm optical zone following PRK., Methods: The records of 95 eyes that had undergone PRK with a 6.0 OZ (n = 40) and a 6.5 OZ (n = 55) were retrospectively reviewed. We compared data including the spherical equivalent of manifest refraction (SE of MR), simulated K (Sim K), thinnest corneal thickness, change in thinnest corneal thickness (the initial value divided by corrected diopter [ΔTCT/CD]), Q value, corneal higher order aberrations (HOAs) and spherical aberration (SA) pre-operation, at 3 and 6 months postoperative and at the last follow-up visit (Mean; 20.71 ± 10.52, 17.47 ± 6.57 months in the 6.0 and 6.5 OZ group, respectively)., Results: There were no significant differences in the SE of MR, Sim K and UDVA between the 6.0 OZ group and the 6.5 OZ group over 1 year of follow-up after PRK, and the 6.0 OZ group required less ΔTCT/CD than the 6.5 OZ group. The 6.5 OZ group showed better results in terms of post-operative HOAs of RMS, SA and Q value. When comparing that pattern of change in Sim K, there was no significant difference between the 6.0 OZ group and the 6.5 OZ group., Conclusions: The clinical refractive outcomes and regression after PRK using Mel 90 excimer laser with a 6.0 OZ were comparable to those with a 6.5 OZ.

Background: The role of subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in perpetuating the COVID-19 pandemic is unknown because population seroprevalence data are absent. We aimed to establish the sensitivity and specificity of our enzyme immunoassay and microneutralisation assay, and the seroprevalence of SARS-CoV-2 in Hong Kong before and after the pandemic, as well as in Hong Kong residents evacuated from Hubei province, China., Methods: We did a multicohort study in a hospital and university in Hong Kong. We evaluated the sensitivity of our enzyme immunoassay and microneutralisation assay with RT-PCR data from patients positive for SARS-CoV-2 and the specificity of our enzyme immunoassay and microneutralisation assay with archived serum samples collected before 2019. We compared the seropositivity of the general population of Hong Kong before and after the pandemic had begun, and determined the seropositivity of Hong Kong residents evacuated from Hubei province, China, in March, 2020., Findings: Between Feb 26 and March 18, 2020, we assessed RT-PCR samples from 45 patients who had recovered from COVID-19 to establish the sensitivity of our enzyme immunoassay and microneutralisation assay. To establish the specificity of these assays, we retrieved archived serum. The sensitivity was 91·1% (41 of 45 [95% CI 78·8-97·5]) for the microneutralisation assay, 57·8% (26 of 45 [42·2-72·3]) for anti-nucleoprotein IgG, 66·7% (30 of 45 [51·1-80·0]) for anti-spike protein receptor binding domain (RBD) IgG, and 73·3% (33 of 45 [58·1-85·4]) for enzyme immunoassay (either positive for anti-nucleoprotein or anti-RBD IgG). The specificity was 100% (152 of 152 [95% CI 97·6-100·0]) for both the enzyme immunoassay and microneutralisation assay. Among the Hong Kong general population, 53 (2·7%) of 1938 were enzyme immunoassay positive, but of those who were positive, all 53 were microneutralisation negative, and no significant increase was seen in the seroprevalence between April 12, 2018, and Feb 13, 2020. Among asymptomatic Hubei returnees, 17 (4%) of 452 were seropositive with the enzyme immunoassay or the microneutralisation assay, with 15 (88%) of 17 seropositive with the microneutralisation assay, and two familial clusters were identified., Interpretation: Our serological data suggest that SARS-CoV-2 is a new emerging virus. The seropositivity rate in Hubei returnees indicates that RT-PCR-confirmed patients only represent a small proportion of the total number of cases. The low seroprevalence suggests that most of the Hong Kong and Hubei population remain susceptible to COVID-19. Future waves of the outbreak are inevitable without a vaccine or antiviral prophylaxis. The role of age-related cross reactive non-neutralising antibodies in the pathogenesis of COVID-19 warrants further investigation., Funding: Richard and Carol Yu, May Tam Mak Mei Yin, Shaw Foundation (Hong Kong), Michael Tong, Marina Lee, and the Government Consultancy Service (see acknowledgments for full list)., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

An amendment to this paper has been published and can be accessed via the original article.

Introduction: Lower transcatheter aortic valve replacement (TAVR) pressure gradients have been reported after implantation of self-expanding valves compared with balloon-expandable valves; however, there is a paucity of data on the relationship between invasively measured transvalvular pressure gradients and Doppler-derived measurements., Methods: From September 2013 to September 2018, patients with native aortic valve stenosis who had both intraoperative invasive and postoperative echocardiography transvalvular pressure gradients were included for analysis. We used parametric and nonparametric statistics to compare aortic gradients within and between groups., Results: Of 171 patients, 152 (88.9%) patients had TAVR with a balloon-expandable valve and 19 (11.1%) with a self-expanding valve. Among all patients, the invasive aortic gradient was 7.8 ± 3.2 mmHg and the Doppler-derived aortic gradient was 11.0 ± 4.5 mmHg (p < 0.001). Among those who received a balloon-expandable valve, the invasive aortic gradient was 7.5 ± 3 mmHg and the Doppler aortic gradient was 11.4 ± 4.5 mmHg (p < 0.001). In contrast, among patients who received a self-expanding valve, the invasive aortic gradient was 10.3 ± 3.4 mmHg and the Doppler aortic gradient was 8.5 ± 4.6 mmHg (p = 0.18)., Conclusions: Balloon-expandable valves were associated with lower invasive measurements versus post-TAVR Doppler gradients, while results were inconclusive regarding self-expanding valves.

This study examined the laxative effects of hot-water extracts of Hovenia dulcis Thunb. (HD), Phyllostachys pubescens Mazel (PM), and a 2:8 mixture of both (HP) in two chronic constipation models. For the loperamide-induced constipation model, animals were divided into an untreated group, negative control group (loperamide 4 mg/kg), positive control group (bisacodyl 4 mg/kg) group, and six treatment groups (HP 100 or 400, HD 50 or 100, and PM 100 or 400 mg/kg). For the lowfiber diet-induced constipation model, animals were divided into an untreated group (normal diet), negative control group (low-fiber diet), positive control group (Agio granule, 620 mg/kg), and the same treatment groups. Fecal number, weight, fecal water content, and intestinal transit ratio were higher in the groups treated with HP, HD, and PM than in the groups treated with loperamide or lowfiber diet. Thickness of colon mucosa and muscle layers were increased in the treated groups. Colon tension increased in the HP groups, and [Ca 2+ ]i measurements using fura-2 as an indicator showed that HP inhibits ATP-mediated Ca 2+ influx in IEC-18 cells. These results showed that the HP mixture has laxative activity by increased mucin secretion and inducing contractile activity and relaxation. It may be a useful therapeutic strategy for ameliorating in chronic constipation.

The rapid decline of a few Emberiza bunting species is increasing conservation concerns, especially in Asia. However, temporal changes in communities and populations of buntings, ones of the most common migratory songbirds in Korea, have not been quantitatively assessed. To understand how the status of buntings has changed over the past 100 years, we collated abundance data from museum collections and bird-banding records between 1910 and 2019. We also used presence-absence data for buntings collected by a nationwide census scheme between 1997 to 2012. Our analysis showed that bunting communities reconstructed from museum-specimen and bird-banding data were not significantly different; however, community composition differed over time. The Meadow (E. cioides), Yellow-throated (E. elegans), Black-faced (E. spodocephala), Rustic (E. rustica) and Chestnut Buntings (E. rutila), which are still common or were once common species, significantly affected the temporal changes in bunting community composition. There were no recent changes in the presence of Rustic and Chestnut Buntings since 1997, but they caused medium-term changes in the bunting community composition, suggesting that there was a sharp to moderate decline in their numbers in the past. The probability of the presence of six bunting species decreased annually, with the most prominent decline in two common breeders, the Meadow (-2.99%/year) and Yellow-throated Buntings (-1.82%/year). This finding suggests that breeding buntings in Korea are under high pressure, as are the migratory buntings. Moreover, despite its recent population decline, the Yellow-throated Bunting was still a major contributor to the community, suggesting that bunting diversity has also been deteriorating while bunting populations are shrinking. Long-term monitoring schemes across their distribution ranges, international cooperation for identifying major threats and key areas of conservation, and law enforcement against illegal hunting and habitat loss are strongly required to mitigate the on-going decline of buntings in Korea and Asia., Competing Interests: The authors declare no conflict of interest.