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Fipronil is a broad-spectrum insecticide widely used in agriculture and residential areas; its indiscriminate use leads to environmental pollution and poses health hazards. Early detection of fipronil is critical to prevent the deleterious effects. However, current insecticide analysis methods such as HPLC, LC/MS, and GC/MS are incompetent; they are costly, immobile, time-consuming, laborious, and need skilled technicians. Hence, a sensitive, specific, and cheap biosensor are essential to containing the contamination. Here, we designed two novel biosensors-the first design relied on fluorescent labeling/quenching, while the second sensor focused on label-free detection using Thioflavin T displacement. Altogether, we identified four candidate aptamers, predicted secondary structures, and performed 3D molecular modeling to predict the binding pocket of fipronil in FiPA6B aptamer. Furthermore, the aptameric sensors showed high sensitivity to fipronil of sub-ppb level LOD, attributed to stringent experimental design. The biosensors displayed high specificity against other phenylpyrazole insecticides and demonstrated robust sensitivity for fipronil in real samples like cabbage and cucumber. Notably, to the best of our knowledge, this is the first demonstration of noncanonical G4-quadruplex-like aptamer binding to fipronil, verified using CD spectroscopy. Such aptasensors possess considerable potential for real-time measurements of hazardous insecticides as point-of-care technology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration., Study Design: Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses., Results: Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69)., Conclusion: Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diazinon is a widely used organophosphorus neurotoxic insecticide. It is a common environmental contaminant and a hazardous agri-waste. Its detection is critical to control entry into food systems and protect the environment., Methods: In this study, three single-stranded DNA aptamers specific for diazinon were discovered using the systematic evolution of ligands by the exponential enrichment (SELEX) process. Since aptamer-based sensors are quick and straightforward to analyze, they could potentially replace the time-consuming and labor-intensive traditional methods used for diazinon detection., Results: Here, we show the engineering of novel sensors for diazinon detection with a high affinity (Kd), specificity, and high sensitivity at the ppb level. Moreover, the aptamers were helpful in the simultaneous detection of two other structurally relevant insecticides, fenthion, and fenitrothion. Furthermore, the real vegetable and fruit samples confirmed the specific detection of diazinon using DIAZ-02., Conclusions: We developed novel biosensors and optimized the assay conditions for the detection of diazinon from food samples, such as vegetables and fruit. The biosensor could be adopted to analyze toxicants and contaminants in food, water, and nature as point-of-care technology., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Liver transplantation (LT) for cholangiocarcinoma (CCA) remains limited to a small number of centers. Although the role of neoadjuvant therapy (NAT) has been explored over time, an in-depth analysis of NAT strategies remains limited. Furthermore, controversy exists regarding acceptable tumor size during patient selection for LT. This study explores the impact of era, tumor size, and NAT strategy on LT outcomes for CCA. We conducted a retrospective review of 53 patients with CCA treated with LT from 1985 to 2019; 19 hilar CCA (hCCA) and 30 intrahepatic CCA (iCCA) were included. The relative contributions of varying NAT (neoadjuvant chemotherapy [NAC], neoadjuvant local therapy [NALT], and combined NAC and NALT [NACLT]) as well as the implication of tumor size and era were analyzed. The primary endpoint was overall survival (OS). Compared with the old era (1985-2007), 5-year OS in patients who underwent LT in the recent era (2008-2019) showed a superior trend. The 5-year OS from initial treatment in patients receiving NACLT for hCCA and iCCA were 88% and 100% versus 9% and 41% in patients without it, respectively (P = 0.01 for hCCA; P = 0.02 for iCCA), whereas NAC or NALT alone did not show significant differences in OS versus no NAT (P > 0.05). Although 33 patients had large-size tumors (hCCA ≥ 30 mm, n = 12, or iCCA ≥ 50 mm, n = 21), tumor size had no impact on survival outcomes. Outcomes of LT for CCA seem to have improved over time. Multimodal NAT is associated with improved survival in LT for both iCCA and hCCA regardless of tumor size., (Copyright © 2021 American Association for the Study of Liver Diseases.)

In the context of coronavirus pandemic (COVID-19), the face-recognition-based access control system (FACS) has been intensively adopted to protect students' and teachers' health and safety in school. However, the impact of FACS, as a new technology, on students' attitude toward accepting FACS has remained unknown from the psychological halo effect. Drawn on "halo effect" theory where psychological effects affect the sense of social identity and belonging, the present study explored college students' sense of school identity and belonging in using FACS during COVID-19 based on the technology acceptance model (TAM). Data collected from 391 college students was analyzed using SEM to verify the relationship among perceived usefulness (PU), perceived ease of use (PEU), intention to use (IU), school identity, and school belonging. The results show that PU and PEU can positively predict IU, and consequentially can positively predict school identity and school belonging. Our study expands the application of halo effect theory to study FACS acceptance based on TAM, and provides strong evidence to support the effect of school FACS during the pandemic. The findings of this study also suggest that FACS acceptance can enhance students' sense of school identity and belonging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Hou, Hong, Yang and Zhang.)

Carbohydrates are produced in green tissues through photosynthesis and then transported to sink tissues. Carbon partitioning is a strategic process, fine regulated, involving specific sucrose transporters in each connecting tissue. Here we report that a screening of an Arabidopsis transcription factor (TF) library using the homeodomain-leucine zipper I member AtHB23 as bait, allowed identifying the TF AtPHL1 interacting with the former. An independent Y2H assay, and in planta by BiFC, confirmed such interaction. AtHB23 and AtPHL1 coexpressed in the pedicel-silique nodes and the funiculus. Mutant plants (phl1, and amiR23) showed a marked reduction of lipid content in seeds, although lipid composition did not change compared to the wild type. While protein and carbohydrate contents were not significantly different between mutants and control mature seeds, we observed a reduced carbohydrate content in mutant plants young siliques (7 days after pollination). Moreover, using a CFDA probe, we revealed an impaired transport to the seeds, and the gene encoding the carbohydrate transporters SWEET10 and SWEET11, usually expressed in connecting tissues, was repressed in the amiR23 and phl1 mutant plants. Altogether, the results indicated that AtHB23 and AtPHL1 act together, promoting sucrose transport, and the lack of any of them provoked a reduction in seeds lipid content., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Disparity in mental health care among cancer patients remains understudied., Methods: A large, retrospective, single tertiary-care institution cohort study was conducted based on deidentified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between January 2012 and September 2019. The exposure of interest was early-onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality., Results: There were 8.2% of patients who received a new MHD at a median of 197 days (interquartile range, 61-553) after incident cancer diagnosis; 31.0% received a PM prescription; and 3.7% a mental health-related visit (MHRV). There were 62.6% of patients who were non-Hispanic White (NHW), 10.8% were Asian, 9.8% were Hispanic, and 3.8% were Black. Compared with NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian odds ratio [OR], 0.66, 95% CI, 0.55-0.78; Black OR, 0.60, 95% CI, 0.45-0.79; Hispanic OR, 0.72, 95% CI, 0.61-0.85) and selective serotonin-reuptake inhibitors (Asian OR, 0.43, 95% CI, 0.37-0.50; Black OR, 0.51, 95% CI, 0.40-0.61; Hispanic OR, 0.79, 95% CI, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR], 1.43, 95% CI, 1.25-1.64) that waned by 24 to 36 months (HR, 1.18, 95% CI, 0.95-1.45)., Conclusions: New mental health diagnosis with PM was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of MHDs or treatment, which may represent missed opportunities to identify and treat cancer-related mental health conditions., (© 2021 American Cancer Society.)

Knowledge sharing is the major driving force to maintain enterprises' competitiveness. This study extends the current knowledge-sharing research by considering knowledge sharing as comprising four types: automatic response, rational reflection, ridiculed reflection, and deprived reflection, based on Kahneman's (2011) types of system thinking. Drawing on the motivation-action-outcome model, this study explored how individuals' intrinsic motivation can guide the action of knowledge sharing and reflect the outcome of creative self-efficacy in intelligent transportation jobs. By snowball sampling in intelligent transportation companies, a total of 232 effective questionnaires were collected, and confirmatory factor analysis with structural equation modeling was performed. The research results showed that: intrinsic motivation was positively related to the four types of knowledge sharing tendencies; automatic response was not significantly related to creative self-efficacy; rational reflection was positively associated with creative self-efficacy; but ridiculed and deprived reflection were negatively related to creative self-efficacy. These results can be applied to encourage employees to practice rational reflection in knowledge sharing to enhance their creative self-efficacy in intelligent transportation jobs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Hong and Ye.)

A great deal of attention has been focused on technological innovation, for example, face recognition, which has been used in some countries in various fields. Nonetheless, there has been little attention paid to parents' acceptance of the use of face recognition systems on campus. To address this gap in the literature, this study examined how different degrees of technological innovativeness and dangerous beliefs in the virtual world (DBVW) influence parents' perceived value of using and intention to continue supporting schools' use of face recognition systems. This study adopted snowball sampling to collect data through questionnaires, and received 380 valid responses from parents living in Xuzhou, China. Confirmatory factor analysis and structural equation modeling were used to analyze the data, with results indicating that: (1) DBVW was negatively related to perceived value; (2) technological innovativeness was positively related to perceived value; and (3) perceived value was positively related to continuance intention to use face recognition systems. The results suggest that parents support the use of face recognition systems in elementary school; thus, such systems can be adopted by other elementary schools in other areas., Competing Interests: Conflict of interestThe authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Remote work has become the most popular approach during the COVID-19 lockdown; however, remote work engagement is an issue which creates challenges for human resource management. Some individuals engage in work no matter how difficult the job is, but some people's minds wander, no matter how simple the job is. To address this issue, this study drew on trait activation theory, which indicates that one's positive disposition may affect one's turnover intention mediated by work engagement, to formulate a research model to test the associations among R&D professionals. Questionnaires were distributed to R&D professionals working in China information and communication technology (ICT) through several Instant Message groups. In total, 386 valid questionnaires were collected for confirmatory factor analysis with structural equation modeling to verify the research model. The study found that positive affect can positively predict three types of remote work engagement: the cognitive, emotional, and behavioral engagement of R&D personnel. All three types of remote work engagement of R&D personnel can negatively predict their turnover intention. The results suggest that if human resource managers working in the ICT industry want to reduce the turnover intention rate of R&D workers under pressure from COVID-19, they should enhance workers' remote engagement by selecting R&D workers with a high level of positive affect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hong, Petsangsri and Cui.)

Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens in a synergistic and interdependent manner, while JA and ET also have independent roles in certain processes, e.g. in responses to wounding and flooding, respectively. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, of which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. We previously demonstrated that Arabidopsis (Arabidopsis thaliana) GDSL LIPASE 1 (GLIP1) depends on ET for gene expression and pathogen resistance. Here, promoter analysis of GLIP1 revealed ERELEE4 as the critical cis-element for ET-responsive GLIP1 expression. In a yeast one-hybrid screening, ORA59 was isolated as a specific transcription factor that binds to the ERELEE4 element, in addition to the well-characterized GCC box. We found that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in gene promoters. Notably, ORA59 exhibited a differential preference for GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. JA and ET induced ORA59 phosphorylation, which was required for both activity and specificity of ORA59. Furthermore, RNA-seq and virus-induced gene silencing analyses led to the identification of ORA59 target genes of distinct functional categories in JA and ET pathways. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Competing interests: JH is coinventor on a pending patent unrelated to this manuscript. FYF has paid consultant/advisory board relationships with Janssen, Sanofi, Astellas, Bayer, Genentech, EMD Serono, Clovis and Celgene, and an unpaid consultant/advisory board relationship with PFS Genomics.

The coronavirus disease 2019 (COVID-19) pandemic has proved the importance of fast and widespread diagnostic testing to prevent serious epidemics timely. The first-line weapon against rapidly transmitted disease is a quick and massive screening test to isolate patients immediately, preventing dissemination. Here, we described magnetoplasmonic nanozymes (MagPlas NZs), i.e., hierarchically coassembled Fe 3 O 4 -Au superparticles, that are capable of integrating magnetic enrichment and catalytic amplification, thereby the assay can be streamlined amenable to high-throughput operation and achieve ultrahigh sensitivity. Combining this advantage with conventional enzyme-linked immunosorbent assay (ELISA), we propose a MagPlas ELISA for urine-based tuberculosis (TB) diagnosis and anti-TB therapy monitoring, which enables fast (<3 h), and highly sensitive (up to pM with naked-eyes, < 10 fM with plate reader) urinary TB antigen detection. A clinical study with a total of 297 urine samples showed robust sensitivity for pulmonary tuberculosis (85.0%) and extra-pulmonary tuberculosis (52.8%) patients with high specificity (96.7% and 96.9%). Furthermore, this methodology offers a great promise of noninvasive therapeutic response monitoring, which is impracticable in the gold-standard culture method. The MagPlas ELISA showed high sensitivity comparable to the PCR assay while retaining a simple and cheap ELISA concept, thus it could be a promising point-of-care test for TB epidemic control and possibly applied to other acute infections., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Alpha-1,6-mannosyl-glycoprotein 2-β- N -acetylglucosaminyltransferase [EC 2.4.1.143, N -acetylglucosaminyltransferase II (GnTII)] catalyzes the transfer of N-acetylglucosamine (GlcNAc) residue from the nucleotide sugar donor UDP-GlcNAc to the α1,6-mannose residue of the di-antennary N-glycan acceptor GlcNAc(Xyl)Man 3 (Fuc)GlcNAc 2 in the Golgi apparatus. Although the formation of the GlcNAc 2 (Xyl)Man 3 (Fuc)GlcNAc 2 N-glycan is known to be associated with GnTII activity in Arabidopsis thaliana , its physiological significance is still not fully understood in plants. To address the physiological importance of the GlcNAc 2 (Xyl)Man 3 (Fuc)GlcNAc 2 N-glycan, we examined the phenotypic effects of loss-of-function mutations in GnTII in the presence and absence of stress, and responsiveness to phytohormones. Prolonged stress induced by tunicamycin (TM) or sodium chloride (NaCl) treatment increased GnTII expression in wild-type Arabidopsis (ecotype Col-0) but caused severe developmental damage in GnTII loss-of-function mutants ( gnt2-1 and gnt2-2 ). The absence of the 6-arm GlcNAc residue in the N-glycans in gnt2-1 facilitated the TM-induced unfolded protein response, accelerated dark-induced leaf senescence, and reduced cytokinin signaling, as well as susceptibility to cytokinin-induced root growth inhibition. Furthermore, gnt2-1 and gnt2-2 seedlings exhibited enhanced N-1-naphthylphthalamic acid-induced inhibition of tropic growth and development. Thus, GnTII's promotion of the 6-arm GlcNAc addition to N-glycans is important for plant growth and development under stress conditions, possibly via affecting glycoprotein folding and/or distribution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yoo, Ko, Vu, Lee, Yoon, Pham, Kim, Lim, Kang, Hong and Lee.)

We describe the challenging perioperative course of a 55-year-old patient with hepatic failure requiring liver transplantation (LT). Different modalities of the extracorporeal device were successfully used, ranging from veno-veno bypass to partial and full veno-veno extracorporeal membrane oxygenation (ECMO) in order to optimize preload, reduce bleeding from the collateral circulation, optimize acid base balance and/or improve oxygenation. The case highlights the potential use of the device as a rescue method in challenging cases. Furthermore this is the first documented case that extracorporeal CO 2 removal (ECCO 2 R) is used to optimize the biochemistry profile intraoperatively during a LT. The patient was weaned off the device at the end of the case and has been discharged home.

In stroke patients, sensory loss often reduces the sensation of ground contact, which impairs motor learning during rehabilitation. In our previous study, we proposed a vibro-tactile biofeedback system (which we called the perception-empathy biofeedback system) for gait rehabilitation. The results of our 9-week pilot clinical test suggested that patients who had reached the autonomous phase in gait learning had difficulty noticing the external vibratory feedback provided by the biofeedback system, leading to ineffective intervention. We considered the possibility that slower walking speed might return the patient to the association phase and allow patients to improve their gait according to the sensory feedback provided. Thus, in this research, a method based on reducing walking speed to guide patients' attention was derived. A pilot clinical trial shows that there is a statistically significant increase of ankle dorsiflexion in the initial contact phase and increase of ankle plantarflexion in the push-off phase after vibro-tactile biofeedback system intervention with speed reduction, compared to intervention without speed reduction. The results suggest that, by reducing their walking speed during intervention, patients return to the association phase and recognize external vibratory feedback, which may result in better intervention effects.Clinical Relevance-This study provides knowledge about the optimal walking speed when using vibro-tactile biofeedback for motor learning in stroke patients.

Raf kinase inhibitory protein (RKIP) is an essential regulator of the Ras/Raf-1/MEK/ERK signaling cascade and functions by directly interacting with the Raf-1 kinase. The abnormal expression of RKIP is linked with numerous diseases including cancers, Alzheimer's and diabetic nephropathy. Interestingly, RKIP also plays an indispensable role as a tumor suppressor, thus making it an attractive therapeutic target. To date, only a few small molecules have been reported to modulate the activity of RKIP, and there is a need to explore additional scaffolds. In order to achieve this objective, a pharmacophore model was generated that explores the features of locostatin, the most potent RKIP modulator. Correspondingly, the developed model was subjected to screening, and the mapped compounds from Marine Natural Products (MNP) library were retrieved. The mapped MNPs after ensuing drug-likeness filtration were escalated for molecular docking, where locostatin was regarded as a reference. The MNPs exhibiting higher docking scores than locostatin were considered for molecular dynamics simulations, and their binding affinity towards RKIP was computed via MM/PBSA. A total of five molecules revealed significantly better binding free energy scores than compared to locostatin and, therefore, were reckoned as hits. The hits from the present in silico investigation could act as potent RKIP modulators and disrupt interactions of RKIP with its binding proteins. Furthermore, the identification of potent modulators from marine natural habitat can act as a future drug-discovery source.

The treatment of osteochondral defects (OCD) remains challenging. Among currently available surgical treatments for OCDs, scaffold-based treatments are promising to regenerate the osteochondral unit. However, there is still no consensus regarding the clinical effectiveness of these scaffold-based therapies for OCDs. Previous reviews have described the gradient physiological characteristics of osteochondral tissue and gradient scaffold design for OCD, tissue engineering strategies, biomaterials, and fabrication technologies. However, the discussion on bridging the gap between the clinical need and preclinical research is still limited, on which we focus in the present review, providing an insight into what is currently lacking in tissue engineering methods that failed to yield satisfactory outcomes, and what is needed to further improve these techniques. Currently available surgical treatments for OCDs are firstly summarized, followed by a comprehensive review on experimental animal studies in recent 5 years on osteochondral tissue engineering. The review will then conclude with what is currently lacking in these animal studies and the recommendations that would help enlighten the community in developing more clinically relevant implants., The Translational Potential of This Article: This review is attempting to summarize the lessons from clinical and preclinical failures, providing an insight into what is currently lacking in TE methods that failed to yield satisfactory outcomes, and what is needed to further improve these implants., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Fenitrothion is an insecticide belonging to the organophosphate family of pesticides that is widely used around the world in agriculture and living environments. Today, it is one of the most hazardous chemicals that causes severe environmental pollution. However, detection of fenitrothion residues in the environment is considered a significant challenge due to the small molecule nature of the insecticide and lack of molecular recognition elements that can detect it with high specificity. We performed in vitro selection experiments using the SELEX process to isolate the DNA aptamers that can bind to fenitrothion. We found that newly discovered DNA aptamers have a strong ability to distinguish fenitrothion from other organophosphate insecticides (non-specific targets). Furthermore, we identified a fenitrothion-specific aptamer; FenA2, that can interact with Thioflavin T (ThT) to produce a label-free detection mode with a K d of 33.57 nM (9.30 ppb) and LOD of 14 nM (3.88 ppb). Additionally, the FenA2 aptamer exhibited very low cross-reactivity with non-specific targets. This is the first report showing an aptamer sensor with a G4-quadruplex-like structure to detect fenitrothion. Moreover, these aptamers have the potential to be further developed into analytical tools for real-time detection of fenitrothion from a wide range of samples.

Interaction between light signaling and stress response has been recently reported in plants. Here, we investigated the role of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a key regulator of light signaling, in endoplasmic reticulum (ER) stress response in Arabidopsis. The cop1-4 mutant Arabidopsis plants were highly sensitive to ER stress induced by treatment with tunicarmycin (Tm). Interestingly, the abundance of nuclear-localized COP1 increased under ER stress conditions. Complementation of cop1-4 mutant plants with the wild-type or variant types of COP1 revealed that the nuclear localization and dimerization of COP1 are essential for its function in plant ER stress response. Moreover, the protein amount of ELONGATED HYPOCOTYL 5 (HY5), which inhibits bZIP28 to activate the unfolded protein response (UPR), decreased under ER stress conditions in a COP1-dependent manner. Accordingly, the binding of bZIP28 to the BIP3 promoter was reduced in cop1-4 plants and increased in hy5 plants compared with the wild type. Furthermore, introduction of the hy5 mutant locus into the cop1-4 mutant background rescued its ER stress-sensitive phenotype. Altogether, our results suggest that COP1, a negative regulator of light signaling, positively controls ER stress response by partially degrading HY5 in the nucleus.

Due to the spread of the epidemic around the world, online learning has received greater attention. Self-regulated learning (SRL) is an important factor for students to achieve academic success. This study investigated the gender differences in SRL and three sub-constructs of SRL in the context of online learning, that is the preparatory, performance, and appraisal phases. A total of 400 high school students (males = 125, females = 275) from China participated in this study. In order to identify whether there were gender differences in their self-regulated online learning (SROL), independent sample t -test was performed. The results showed that there were significant gender differences in the SROL ( t = -3.334, p = 0.001 < 0.01, d = -0.410) and the three sub-constructs of SROL (preparatory: t = -0.702, p = 0.008 < 0.01, d = 0.018; performance: t = -3.801, p = 0.000 < 0.01, d = 0.456; appraisal: t = -3.120, p = 0.002 < 0.01, d = 0.361). The findings indicated that females performed better than males in all three dimensions of learners' online self-regulated learning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, He, Zhao and Hong.)

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 μm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Due to the COVID-19 pandemic, online learning has been adopted in all stages of education. This sudden change from traditional learning to 100% online learning may affect students' learning effectiveness, especially in experimental courses. However, there has been little discussion of experimental courses conducted entirely through online learning. To address this gap, the present study investigated factors affecting high school students' online learning ineffectiveness (OLI) in online experimental courses, particularly online science experimental courses. The role of gender was also explored to understand whether it affects participants' OLI. An ANOVA was conducted to analyze the data from a survey of 347 online learners in high schools. The results indicated that the number of online experimental courses and the duration of online hands-on learning were negatively related to the high school students' OLI. Meanwhile, the study found that the high school participants' OLI differed by gender, with female students more likely than males to have OLI in the context of online learning. The results of this study can provide a reference for teachers who conduct online experimental courses and wish to improve their online teaching, not only during the COVID-19 lockdown, but also in other pandemic periods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hong, Liu, Liu and Zhao.)

Although intelligence beliefs have been applied to explain the influence of cognition, behavior, and creativity, the research on creativity is still limited. Therefore, in order to effectively expand the understanding of the influence of intelligence beliefs on the creative performance of learners' graphics, the implicit theories of intelligence were exploited as the basis of this study. Three hypothetical pathways were proposed to be explored, and a research model was validated. First- and second-year students from a technical high school in New Taipei City were invited to participate. There were 273 valid data (88.9% of complete data). Reliability and validity analyses were performed, as well as overall model fit analysis and research model validation, and descriptive statistical analysis of the learners' performance in applying the operational virtual reality (VR). The results of this study showed that: (1) Incremental beliefs of aesthetic intelligence had a positive effect on spatial performance; (2) entity belief of spatial intelligence (EBSI) had a negative effect on spatial performance; and (3) spatial performance had a positive effect on graphical design performance. From the results, it is clear that design teachers can assess students' implicit beliefs in the early stages of teaching to actively promote better spatial performance when students show high levels of entity beliefs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hong, Ye, Chen, Ye and Kung.)

Protein-level regulations have gained importance in building synthetic circuits, as they offer a potential advantage in the speed of operation compared to gene regulation circuits. In nature, localized protein degradation is prevalent in polarizing cellular signaling. We, therefore, set out to systematically investigate whether localized proteolysis can be employed to construct intracellular asymmetry in Escherichia coli . We demonstrate that, by inserting a cognate cleavage site between the reporter and C-terminal degron, the unstable reporter can be stabilized in the presence of the tobacco etch virus protease. Furthermore, the split protease can be functionally reconstituted by the PopZ-based polarity system to exert localized proteolysis. Selective stabilization of the unstable reporter at the PopZ pole can lead to intracellular asymmetry in E. coli . Our study provides complementary evidence to support that localized proteolysis may be a strategy for polarization in developmental cell biology. Circuits designed in this study may also help to expand the synthetic biology repository for the engineering of synthetic morphogenesis, particularly for processes that require rapid control of local protein abundance.

Different approaches to stimulating perceptions in learning can be easily designed with technology-enhanced learning systems. This study aimed to explore how different approaches can influence learners' perceptions that may negatively or positively affect their learning performance of writing Chinese characters using the correct Chinese order of strokes (COS). We therefore designed an e-learning system which was subdivided into two modes: stroke-appearing (i.e., using red to mark incorrect strokes) and stroke-disappearing (i.e., using blanks to mark incorrect strokes) to indicate strokes written in the incorrect order. We then investigated the modes that would facilitate a higher level of attention and better learning outcomes. A total of 10 third-grade elementary school students participated in the experiment, divided into two test groups. Their EEG data were collected, and time series analysis and t -tests were utilized to analyze the differences. The results indicated that: (1) there was a significant difference in the attention levels of the students practicing with the stroke-appearing and stroke-disappearing modes when learning COS, and (2) there was a significant difference in the learning outcomes of the students practicing with the stroke-appearing and stroke-disappearing modes when learning COS. These findings support the specific role of stroke order knowledge in learning Chinese characters and the need for the design of an effective method for teaching children to learn Chinese characters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hong, Tai, Hwang and Lin.)

The highly contagious Covid-19 virus is spreading around the world, and quarantining at home has become one of the main preventative behaviors, but it has also led to news blackouts, affecting people's normal life and interactions. In order to determine a predictor of cellphone addiction (CPA), the present study, based on the Risk of Information Seeking and Processing (RISP) model, investigated the relationship between personality (Neuroticism and Extraversion) and CPA during the epidemic, mediated by online social anxiety (OSA) and cyber danger belief (CDB). A total of 683 questionnaires were collected through snowball sampling and analyzed by Mplus. Results indicated that neurotic and extroverted individuals developed CPA through different mediating factors. Neuroticism affected CPA through OSA while Extraversion affected CPA through CDB. These findings highlight the importance of different mechanisms of individuals with different personalities. Corresponding cognitive treatments on the perception of social anxiety and cyber danger are recommended on neurotic and extroverted individuals, respectively, in order to reduce their degree of CPA., (© 2021 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic has caused great disruption in education systems around the world. Schools have in some cases ended or limited on-site teaching, and have shifted toward home online teaching. This situation is likely to cause increased uncertainty and anxiety for parents who on one hand may question the quality of home online learning yet, on the other, may not feel sufficiently confident or competent to guide their children's home online learning. Resulting anxiety is expected to be most evident in competitive educational contexts, such as those found throughout much of East Asia. Therefore, using China as the setting, and social comparison theory as the framework, this study examined how variation in parent social comparison relates to parent tutoring anxiety and, in turn, to the types of guided strategies parents use to promote their children's home online learning. The results indicated a positive relationship between parental upward social comparison and parental tutoring anxiety, but a negative relationship between parent downward social comparison and parental anxiety. Parental tutoring anxiety is positively related to the confirmation and structure types, but negatively related to the discovery type of guided approaches. The implication of this study is that parents who resist tendencies of competitive upward social comparison are likely to adopt more effective approaches to guiding their children's home online learning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Gu and Hong.)

The interactive effects of six maturity stages and refrigerated storage (chilling)/blanching (heating) treatments on the volatile profiles of ripe tomatoes were studied. A total of 42 volatiles were identified, of which 19 compounds had odor activity values equal to or greater than 1. Of those, "green" and "leafy" aroma volatiles were most abundant. Chilling and heating treatments both suppressed overall volatile production, with chilling having the greater impact, regardless of harvest maturity. However, fruit harvested at the turning stage had the least volatile suppression by chilling and heating treatments in comparison with fruit harvested earlier or later, mostly in the fatty acid- and phenylalanine-derived volatiles. Volatiles derived from amino acids were promoted by heat treatment for fruit harvested at all maturities, and those derived from carotenoid and phenylalanine pathways and harvested at advanced harvest maturities were stimulated by chilling treatment. Volatile production is generally believed to be improved by delayed harvest, with vine-ripe being optimum. However, opposite results were observed possibly because the later-harvested fruit had longer exposure to open-field weather stress. The best harvest maturity recommendation is the turning stage where fruit developed abundant volatiles and were least impacted by chilling and heating treatments.

Despite widespread adoption of electronic health records (EHRs), most hospitals are not ready to implement data science research in the clinical pipelines. Here, we develop MEDomics, a continuously learning infrastructure through which multimodal health data are systematically organized and data quality is assessed with the goal of applying artificial intelligence for individual prognosis. Using this framework, currently composed of thousands of individuals with cancer and millions of data points over a decade of data recording, we demonstrate prognostic utility of this framework in oncology. As proof of concept, we report an analysis using this infrastructure, which identified the Framingham risk score to be robustly associated with mortality among individuals with early-stage and advanced-stage cancer, a potentially actionable finding from a real-world cohort of individuals with cancer. Finally, we show how natural language processing (NLP) of medical notes could be used to continuously update estimates of prognosis as a given individual's disease course unfolds., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Protein-protein interactions are indispensable physiological processes regulating several biological functions. Despite the availability of structural information on protein-protein complexes, deciphering their complex topology remains an outstanding challenge. Raf kinase inhibitory protein (RKIP) has gained substantial attention as a favorable molecular target for numerous pathologies including cancer and Alzheimer's disease. RKIP interferes with the RAF/MEK/ERK signaling cascade by endogenously binding with C-Raf (Raf-1 kinase) and preventing its activation. In the current investigation, the binding of RKIP with C-Raf was explored by knowledge-based protein-protein docking web-servers including HADDOCK and ZDOCK and a consensus binding mode of C-Raf/RKIP structural complex was obtained. Molecular dynamics (MD) simulations were further performed in an explicit solvent to sample the conformations for when RKIP binds to C-Raf. Some of the conserved interface residues were mutated to alanine, phenylalanine and leucine and the impact of mutations was estimated by additional MD simulations and MM/PBSA analysis for the wild-type (WT) and constructed mutant complexes. Substantial decrease in binding free energy was observed for the mutant complexes as compared to the binding free energy of WT C-Raf/RKIP structural complex. Furthermore, a considerable increase in average backbone root mean square deviation and fluctuation was perceived for the mutant complexes. Moreover, per-residue energy contribution analysis of the equilibrated simulation trajectory by HawkDock and ANCHOR web-servers was conducted to characterize the key residues for the complex formation. One residue each from C-Raf (Arg398) and RKIP (Lys80) were identified as the druggable "hot spots" constituting the core of the binding interface and corroborated by additional long-time scale (300 ns) MD simulation of Arg398Ala mutant complex. A notable conformational change in Arg398Ala mutant occurred near the mutation site as compared to the equilibrated C-Raf/RKIP native state conformation and an essential hydrogen bonding interaction was lost. The thirteen binding sites assimilated from the overall analysis were mapped onto the complex as surface and divided into active and allosteric binding sites, depending on their location at the interface. The acquired information on the predicted 3D structural complex and the detected sites aid as promising targets in designing novel inhibitors to block the C-Raf/RKIP interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Parate, Rampogu, Lee, Hong and Lee.)

This paper proposes the fabrication process of the first fully 3D-printed ceramic core structures for portable solar desalination devices optimized to tackle water scarcity from an energy and sustainability perspective. Robocasting, a 3D printing technique, is utilized to fabricate a fully ceramic structure of an integrated solar absorber/thermal insulator/water transporter based on the two-layered structure of modified graphene on silica (MG@Silica) and the porous silica structure. Robocasting has demonstrated its flexibility in tailoring structural designs, combining nanopores and microchannels that exhibit uniform water transport delivery and thermal insulation. This portable device can be used immediately to collect fresh drinking water without an additional setup. It possesses a water evaporation rate of 2.4 kg m -2 h -1 with a drinking water production capacity of 0.5 L m -2 h -1 . This novel device has shown excellent ion rejection ability, with the collected water meeting the World Health Organization (WHO) drinking water standards.

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid. Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation. Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7-23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319-23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461-12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426-15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729-0.902). Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Sun, Li, Cai, Li, Hong, Li, Xu, Li, Xue, Gu, Wu, Zhou, Suo, Duan, Wu and Li.)

Liver injury is one of the nonpulmonary manifestations described in coronavirus disease 2019 (COVID-19). Post-COVID-19 cholangiopathy is a special entity of liver injury that has been suggested as a variant of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). In the general population, the outcome of SSC-CIP has been reported to be poor without orthotopic liver transplantation (OLT). However, the role of OLT for post-COVID-19 cholangiopathy is unknown. We present a case report of a 47-year-old man who recovered from acute respiratory distress syndrome from COVID-19 and subsequently developed end-stage liver disease from post-COVID-19 cholangiopathy. The patient underwent OLT and is doing well with normal liver tests for 7 months. To our knowledge, this is the first case report of a patient who underwent successful liver transplantation for post-COVID-19 cholangiopathy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Porous scaffolds have been widely used for bone tissue engineering (BTE), and the pore structure of scaffolds plays an important role in osteogenesis. Silk fibroin (SF) is a favorable biomaterial for BTE due to its excellent mechanical property, biocompatibility, and biodegradation, but the lack of cell attachment sites in SF chemical structure resulted in poor cell-material interactions. In this study, SF scaffolds were coated with fibronectin/gelatin (Fn/G) to improve cell adhesion. Furthermore, the effect of pore size in Fn/G coated SF scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were investigated in vitro. Scaffolds with average pore diameters of 384.52, 275.23, and 173.8 μm were prepared by salt leaching method, labelled as Large, Medium, and Small group. Porcine BMSCs were seeded on scaffolds and cultured in osteogenic medium for 21 days to evaluate cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, gene expression of osteogenic markers, and histological performance. The results showed Fn/G coating effectively improved cell adhesion on SF scaffolds. Cell metabolic rate in each group increased significantly with time, but there was no statistical difference at each time point among the three groups. On day 21, ALP/DNA and calcium/DNA in the Small group were significantly higher than those in the Large group. Among the three pore sizes, the Small group showed higher mRNA expression of COl I on day 7, OPN on day 14, and OCN on day 21. Immunohistochemical staining on day 21 showed that Col I and OCN in Small group were more highly expressed. In conclusion, the Fn/G coated SF scaffolds with a mean pore diameter of 173.8 μm was optimal for osteogenic differentiation of BMSC in vitro., (Copyright © 2021 Elsevier B.V. All rights reserved.)

During the lockdown due to SARS-CoV-2 (coronavirus lockdown), there has been a tremendous increase in the number of students taking online courses. Few studies, however, have examined the individual dispositions that influence self-regulated online learning during the coronavirus lockdown. To address this gap, the present study explored the ineffectiveness of online learning and examined how it can be predicted by self-regulated online learning and participants' procrastination disposition. Data of 433 participants were collected and subjected to confirmatory factor analysis with structural equation modeling. The results indicated that procrastination is negatively related to 6 sub-constructs of self-regulated online learning: task strategy, mood adjustment, self-evaluation, environmental structure, time management, and help-seeking. These sub-constructs were negatively related to the learners' perceived ineffectiveness of online learning. However, the relationship between perceived learning ineffectiveness and environmental structure or help-seeking was weaker than that with task strategy or mood adjustment, indicating that the latter two subtypes of self-regulated online learning should be considered before students engage in online learning., (© 2021 Elsevier Ltd. All rights reserved.)

Significance: Real-time information about oxygen delivery to the hepatic graft is important to direct care and diagnose vascular compromise in the immediate post-transplant period., Aim: The current study was designed to determine the utility of visible diffuse reflectance spectroscopy (vis-DRS) for measuring liver tissue saturation in vivo., Approach: A custom-built vis-DRS probe was calibrated using phantoms with hemoglobin (Hb) and polystyrene microspheres. Ex vivo (extracorporeal circulation) and in vivo protocols were used in a swine model (n  =  15) with validation via blood gas analysis., Results: In vivo absorption and scattering measured by vis-DRS with and without biliverdin correction correlated closely between analyses. Lin's concordance correlation coefficients are 0.991 for μa and 0.959 for μs  '  . Hb measured by blood test and vis-DRS with (R2  =  0.81) and without (R2  =  0.85) biliverdin correction were compared. Vis-DRS data obtained from the ex vivo protocol plotted against the PO2 derived from blood gas analysis showed a good fit for a Hill coefficient of 1.67 and P50  =  34  mmHg (R2  =  0.81). A conversion formula was developed to account for the systematic deviation, which resulted in a goodness-of-fit R2  =  0.76 with the expected oxygen dissociation curve., Conclusions: We show that vis-DRS allows for real-time measurement of liver tissue saturation, an indicator for liver perfusion and oxygen delivery.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background: In order to counter the lack of sufficient kidney donors, there has been interest in expanding the utilization of organs from increased infectious-risk donors. Negative nucleic acid testing of increased infectious-risk organs has been shown to increase their use as compared to only enzyme-linked immunosorbent assay negativity. However, it is not known how the expanded use of nucleic acid testing on a national scale might affect total donor utilization., Objective: The objective of this paper was to determine if a national screening policy requiring the use of nucleic acid testing in both increased infectious-risk and non-increased infectious-risk renal transplant donors would increase the donor organ pool., Methods: This study used decision-tree analysis to determine the cost-effectiveness of four US national screening policies based on an increasingly expansive use of nucleic acid testing for increased infectious-risk and non-increased infectious-risk kidneys. Parameters were taken from the literature. All costs were reported in 2020 US dollars using a Medicare payer perspective and a life-time horizon., Results: The use of nucleic acid screening solely for increased infectious-risk organs was the dominant strategy. Our results were robust to deterministic and probabilistic sensitivity analyses. One of the main driving factors of cost-effectiveness was the false-positive rate of nucleic acid testing., Conclusion: Before implementing nucleic acid screening outside of increased infectious-risk organs, its false-positivity rate should be directly studied to ensure that its use does not detrimentally affect transplantation numbers, quality-adjusted life-years, and costs.

Plant resistance proteins recognize cognate pathogen avirulence proteins (also named effectors) to implement the innate immune responses called effector-triggered immunity. Previously, we reported that hopA1 from Pseudomonas syringae pv. syringae strain 61 was identified as an avr gene for Arabidopsis thaliana . Using a forward genetic screen approach, we cloned a hopA1- specific TIR-NBS-LRR class disease resistance gene, RESISTANCE TO PSEUDOMONAS SYRINGAE6 ( RPS6 ). Many resistance proteins indirectly recognize effectors, and RPS6 is thought to interact with HopA1 Pss61 indirectly by surveillance of an effector target. However, the involved target protein is currently unknown. Here, we show RPS6 is the only R protein that recognizes HopA1 Pss61 in Arabidopsis wild-type Col-0 accession. Both RPS6 and HopA1 Pss61 are co-localized to the nucleus and cytoplasm. HopA1 Pss61 is also distributed in plasma membrane and plasmodesmata. Interestingly, nuclear localization of HopA1 Pss61 is required to induce cell death as NES- HopA1 Pss61 suppresses the level of cell death in Nicotiana benthamiana . In addition, in planta expression of hopA1 Pss61 led to defense responses, such as a dwarf morphology, a cell death response, inhibition of bacterial growth, and increased accumulation of defense marker proteins in transgenic Arabidopsis. Functional characterization of HopA1 Pss61 and RPS6 will provide an important piece of the ETI puzzle.

Plants possess adaptive reprogramed modules to prolonged environmental stresses, including adjustment of metabolism and gene expression for physiological and morphological adaptation. CCoAOMT1 encodes a caffeoyl CoA O-methyltransferase and is known to play an important role in adaptation of Arabidopsis plants to prolonged saline stress. In this study, we showed that the CCoAOMT1 gene plays a role in drought stress response. Transcript of CCoAOMT1 was induced by salt, dehydration (drought), and methyl viologen (MV), and loss of function mutants of CCoAOMT1 , ccoaomt1-1, and ccoaomt1-2 exhibit hypersensitive phenotypes to drought and MV stresses. The ccoaomt1 mutants accumulated higher level of H 2 O 2 in the leaves and expressed lower levels of drought-responsive genes including RD29B , RD20 , RD29A , and ERD1, as well as ABA3 3 and NCED3 encoding ABA biosynthesis enzymes during drought stress compared to wild-type plants. A seed germination assay of ccoaomt1 mutants in the presence of ABA also revealed that CCoAOMT1 functions in ABA response. Our data suggests that CCoAOMT1 plays a positive role in response to drought stress response by regulating H 2 O 2 accumulation and ABA signaling.

Understanding patient accumulation of comorbidities can facilitate healthcare strategy and personalized preventative care. We applied a directed network graph to electronic health record (EHR) data and characterized comorbidities in a cohort of healthy veterans undergoing screening colonoscopy. The Veterans Affairs Cooperative Studies Program #380 was a prospective longitudinal study of screening and surveillance colonoscopy. We identified initial instances of three-digit ICD-9 diagnoses for participants with at least 5 years of linked EHR history (October 1999 to December 2015). For diagnoses affecting at least 10% of patients, we calculated pairwise chronological relative risk (RR). iGraph was used to produce directed graphs of comorbidities with RR > 1, as well as summary statistics, key diseases, and communities. A directed graph based on 2210 patients visualized longitudinal development of comorbidities. Top hub (preceding) diseases included ischemic heart disease, inflammatory and toxic neuropathy, and diabetes. Top authority (subsequent) diagnoses were acute kidney failure and hypertensive chronic kidney failure. Four communities of correlated comorbidities were identified. Close analysis of top hub and authority diagnoses demonstrated known relationships, correlated sequelae, and novel hypotheses. Directed network graphs portray chronologic comorbidity relationships. We identified relationships between comorbid diagnoses in this aging veteran cohort. This may direct healthcare prioritization and personalized care.

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.

Background: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA., Study Design: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis., Results: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001)., Conclusions: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)