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Background: Long-term oral dasatinib administration can induce pulmonary arterial hypertension (PAH) in pediatric patients with Philadelphia chromosome-positive (Ph ) acute lymphoblastic leukemia (ALL). We describe the findings in two pediatric cases involving Ph ALL patients who developed cardiovascular events such as PAH after dasatinib treatment, and present a review of the related literature. Case presentation: Two pediatric patients diagnosed with B-cell ALL ( BCR-ABL P190 fusion gene positive) received conventional chemotherapy and imatinib simultaneously, which was then changed to dasatinib because of a partial response. The two patients developed PAH after 18 months and 6 years of dasatinib therapy. All signs and symptoms improved after immediate discontinuation of dasatinib and symptomatic treatment. Conclusions: Pediatric Ph ALL patients receiving dasatinib should be carefully monitored for serious cardiopulmonary and vascular events such as PAH. Development of adverse reactions should be followed by immediate and permanent discontinuation of oral dasatinib. Dynamic monitoring by echocardiography is recommended when administering dasatinib for maintenance therapy.

Stem cell antigen Sca-1 is implicated in murine cancer stem cell biology and breast cancer models, but the role of its human homologs Ly6K and Ly6E in breast cancer are not established. Here we report increased expression of Ly6K/E in human breast cancer specimens correlates with poor overall survival, with an additional specific role for Ly6E in poor therapeutic outcomes. Increased expression of Ly6K/E also correlated with increased expression of the immune checkpoint molecules PDL1 and CTLA4, increased tumor-infiltrating T regulatory cells, and decreased natural killer (NK) cell activation. Mechanistically, Ly6K/E was required for TGFβ signaling and proliferation in breast cancer cells, where they contributed to phosphorylation of Smad1/5 and Smad2/3. Furthermore, Ly6K/E promoted cytokine-induced PDL1 expression and activation and binding of NK cells to cancer cells. Finally, we found that Ly6K/E promoted drug resistance and facilitated immune escape in this setting. Overall, our results establish a pivotal role for a Ly6K/E signaling axis involving TGFβ in breast cancer pathophysiology and drug response, and highlight this signaling axis as a compelling realm for therapeutic invention. Cancer Res; 76(11); 3376–86. ©2016 AACR.

Table S1: List of qRT-PCR primers; Table. S2: Summary table of mRNA expression for Ly6K and Ly6E in normal and cancer samples in seven comparison; Fig. S1. Expression of Ly6K and Ly6E in human normal and breast cancer tissues; Fig. S2: The knockdown for Ly6K and Ly6E is specific; Fig. S3: Colony assay; Fig. S4: The Ly6K gene is required for intravasation, extravasation and colonization of cancer cells; Fig. S5: Comparison of CD274, CTLA4, IL2RA, LY6E and LY6K gene expression in clinical samples of breast cancer in indicated 6 analysis in three different datasets; Fig. S6: High expression of Ly6K and Ly6E impair NK cell binding to cancer cell; Fig. S7: Indicated cells (MDA-MB-231) were treated with 100ng/ml IFN-g overnight; Fig. S8: Rescue over expression phenotype.

Objectives To investigate the clinical features of thrombotic microangiopathy associated with allogeneic hematopoietic stem cell transplantation in children. Methods A retrospective analysis of continuous clinical data from HSCT received in the Department of Hematology and Oncology of Wuhan Children's Hospital from August 1, 2016 to December 31, 2021. Results During this period, 209 patients received allo-HSCT in our department, 20 (9.6%) of whom developed TA-TMA. TA-TMA was diagnosed at a median of 94 (7–289) days post-HSCT. Eleven (55%) patients had early TA-TMA within 100 days post-HSCT, while the other 9 (45%) patients had TA-TMA thereafter. The most common symptom of TA-TMA was ecchymosis (55%), while the main signs were refractory hypertension (90%) and multi-cavity effusion (35%). Five (25%) patients had central nervous system symptoms (convulsions and lethargy). All 20 patients had progressive thrombocytopenia, with 16 patients receiving transfusion of platelets that was ineffective. Ruptured red blood cells were visible in only two patients with peripheral blood smears. Cyclosporine A or Tacrolimus (CNI) dose was reduced once TA-TMA was diagnosed. Nineteen cases were treated with low-molecular-weight heparin, 17 patients received plasma exchange, and 12 patients were treated with rituximab. TA-TMA-related mortality percentage in this study was 45% (9/20). Conclusion Platelet decline and/or ineffective transfusion post-HSCT should be considered an early indicator of TA-TMA in pediatric patients. TA-TMA in pediatric patients may occur without evidence of peripheral blood schistocytes. Aggressive treatment is required once diagnosis is confirmed, but the long-term prognosis is poor.

Historically, a neutralization antibody (NAb) assay is considered critical in immunogenicity assessment of biologic therapeutics, even with low anti-drug antibody (ADA) positive rates. In 2019, FDA new guidelines issued on immunogenicity testing acknowledged the possibility of using "a highly sensitive PD marker or an appropriately designed PK assay or both that generate data that inform clinical activity" to replace a NAb assay. In the current manuscript, we present data for PK, PD, and ADA assays which collectively succeed to replace the standalone NAb assay. The data include a total LC/MS-based PK assay, a serum neutralization antibody (SNA) assay that essentially measures pharmacodynamically functional PK and can detect NAb activity in the presence of 1:1 ratio of drug, and a highly drug-tolerant ADA assay. In addition, a model-based meta-analysis (MBMA) demonstrated that the ability of SNA assay to detect NAb at 1:1 ratio of drug is sensitive enough to monitor clinically meaningful efficacy change, which is 50% reduction of SNA titer. Our strategy of preparing a holistic data package discussed here may provide a roadmap to the community for alternatives in assaying neutralizing activity of ADA.

The purpose of this study was to determine how graphic organizer completeness (complete, partial, or no organizer) and note-taking medium (longhand or computer) affect note-taking quantity and quality and affect computer-based learning. College students were presented with a computer-based PowerPoint lesson accompanied by complete, partial, or no graphic organizers. Throughout the lesson, students recorded notes using either longhand or computer mediums. Students were tested immediately following the lesson and again two days later following a review period during which graphic organizers and notes were studied. Finally, students completed a survey. Results revealed that organizer completeness affected achievement. Those given complete organizers generally achieved more than those with partial or no organizers across fact-, relationship-, concept-, and skill-based test items. Note-taking medium did not affect achievement differentially, but there were important note-taking findings. Longhand note takers recorded more lesson ideas in notes and had fewer verbatim strings in notes (reflective of more generative processing) compared to computer note takers. Moreover, longhand note takers reported more positive attitudes about their note-taking medium than did computer note takers. Results suggested that complete organizers aid germane load more than partial organizers and that longhand note taking results in deeper processing than does computer note taking. Therefore, instructors should provide complete organizers to promote student learning and should encourage students to take longhand notes when they learn in a computer-based learning environment.

Although nonprecious metal catalysts based on earth-abundant 3d transition metals (TMs) are regarded as promising substitutes for a noble metal electrocatalytic hydrogen evolution reaction (HER), their large-scale application is still inhibited by their inadequate activity and durability. Here, a facile method for nonprecious metal catalysts has been developed to prepare molybdenum carbide on nitrogen-doped carbon. By optimizing the Ni doping ratio, the Ni0.5@MoCx/NC exhibits the lowest overpotential for 10 mA cm-2 and superior stability in both acidic and alkaline media for HER application, outperforming most of the reported HER electrocatalysts. In addition, a theoretical simulation has also confirmed the possible mechanism for the synergistic effect with the regulative adsorption energy of hydrogen species with Ni doping and formation of a Mo2C/MoC heterojunction in the Ni0.5@MoCx/NC electrocatalyst. Therefore, this work provides a new avenue for designing two-dimensional nanostructures with an optimized electronic structure for promising TM HER electrocatalysts in a wide pH range.

Current status data occur in many fields including demographical, epidemiological, financial, medical, and sociological studies. We consider the regression analysis of current status data with latent variables. The proposed model consists of a factor analytic model for characterizing latent variables through their multiple surrogates and an additive hazard model for examining potential covariate effects on the hazards of interest in the presence of current status data. We develop a borrow-strength estimation procedure that incorporates the expectation-maximization algorithm and correlated estimating equations. The consistency and asymptotic normality of the proposed estimators are established. A simulation study is conducted to evaluate the finite sample performance of the proposed method. A real-life study on the chronic kidney disease of type 2 diabetic patients is presented.

Aim: To compare secondary systemic treatment (SST) continuation and associated resource use and costs in chronic graft-versus-host disease (cGvHD) patients in the USA. Materials & methods: This was a retrospective study using Truven Health MarketScan database (2009–2016). cGvHD patients were classified as continuers or discontinuers if treated with SST for ≥180 days without or with a treatment gap (≥45 days), respectively. Results: Among 464 cGvHD patients with SST, mTOR inhibitors, extracorporeal photopheresis and imatinib were most frequently used. A total of 172 patients were SST continuers and 292 were discontinuers. Extracorporeal photopheresis treated patients were the highest continuers, followed by imatinib and mTOR inhibitors. SST continuers had lower monthly hospitalization costs versus discontinuers. Conclusion: This real-world analysis demonstrates high SST continuation rates in cGvHD patients are associated with lower resource utilization and cost.

Eric Armbrecht,1 Ruchit Shah,2 Gregory W Poorman,2 Linlin Luo,2 Jennifer M Stephens,2 Benjamin Li,3 Elizabeth Pappadopulos,4 Seema Haider,5 Roger S McIntyre6– 9 1Saint Louis University Center for Health Outcomes Research, Saint Louis University, Saint Louis, MO, USA; 2Pharmerit International, Bethesda, MD, USA; 3Pfizer Inc., New York, NY, USA; 4Viatris Inc., New York, NY, USA; 5Pfizer Inc., Groton, CT, USA; 6Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; 7Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 8Department of Pharmacology, University of Toronto, Toronto, ON, Canada; 9Brain and Cognition Discovery Foundation, Toronto, ON, CanadaCorrespondence: Jennifer M StephensPharmerit International, 4350 East West Hwy #1100, Bethesda, MD, 20814, USATel +1-240-821-1290Email JenniferStephens@openhealthgroup.comIntroduction: Patients with both major depressive disorder (MDD) and generalized anxiety disorder (GAD) in addition to one or multiple comorbid non-communicable chronic diseases (NCCDs)face unique challenges. However, few studies have characterized how the burden of co-occurring MDD and GAD differs from that of only MDD or only GAD among patients with NCCDs.Methods: In this study, we used Medical Expenditures Panel Survey data from 2010– 2017 to understand how the economic and humanistic burden of co-occurring MDD and GAD differs from that of MDD or GAD alone among patients with NCCDs. We used generalized linear models to investigate this relationship and controlled for patient sociodemographics and clinical characteristics.Results: Co-occurring MDD and GAD was associated with increases in mean annual per patient inpatient visits, office visits, emergency department visits, annual drug costs, and total medical costs. Among patients with 3+ NCCDs, MDD or GAD only was associated with lower odds ratios (ORs) of limitations in activities of daily living (ADLs; 0.532 and 0.508, respectively) and social (0.503, 0.526) and physical limitations (0.613, 0.613) compared to co-occurring MDD and GAD. Compared to patients with co-occurring MDD and GAD, having MDD only or GAD only was associated with significantly lower odds of cognitive limitations (0.659 and 0.461, respectively) in patients with 1– 2 NCCDs and patients with 3+ NCCDs (0.511, 0.416).Discussion: Comorbid MDD and GAD was associated with higher economic burden, lower quality of life, and greater limitations in daily living compared to MDD or GAD alone. Health-related economic and humanistic burden increased with number of NCCDs.Keywords: economic burden, humanistic burden, depression, anxiety, non-communicable diseases

Perovskite oxides have attracted great attention in electrochemistry due to their compositional and structural flexibility. Herein, microwave/ultrasound assisted hydrothermal procedures were developed to synthesize Ce-doped LaCoO3 perovskite oxide as bifunctional electrocatalysts for OER and HER application, achieving highly efficient bifunctional catalytic performance. The obtained LCC4 exhibited excellent electrocatalytic activity with an overpotential of 380 mV and 305 mV at 10 mA cm-2 toward OER and HER, respectively. The lower Tafel slopes of 80 mV per decade and 144 mV per decade for OER and HER, respectively, indicated the faster reaction kinetics for the improved inherent electrocatalytic activity. The outstanding long-term durability of LCC4 in alkaline conditions was also vital to the practical applications of water electrolysis. The improved bifunctional electrocatalytic activity was attributed to the synergistic effects of excellent conductivity and enriched active sites arising from A-site substitution. This work not only provides an efficient strategy for the development of perovskite oxide-based electrocatalysts but also puts forward a new insight on bifunctional electrocatalysts for overall water splitting.

Janus kinase 1 (JAK1) is a member of the JAK family, which plays an essential and non-redundant role in tumorigenesis. However, the potential role of JAK1 in immune infiltration and prognosis of lung adenocarcinoma (LUAD) remains unclear. The mRNA expression and methylation level of JAK1 in LUAD were examined using the Oncomine and The Cancer Genome Atlas (TCGA) databases, respectively. The correlations between JAK1 expression and its methylation level and clinicopathological parameters were analyzed. The Kaplan-Meier plotter database was used to evaluate the prognostic value of JAK1 in LUAD. The signaling pathways associated with JAK1 expression were identified by performing a GSEA. The CIBERSORT and TIMER databases were used to analyze the correlations between JAK1 and tumor-infiltrating immune cells. In addition, the JAK1 expression and proportion of immune cells in LUAD cell lines were analyzed. The JAK1 expression was remarkably decreased in patients with LUAD and significantly correlated with the clinical features of patients with LUAD. The JAK1 methylation level was increased and negatively correlated with its mRNA expression. A decrease in JAK1 expression was correlated with poor prognosis. The results of GSEA showed that cell adhesion, tumorigenesis, and immune-related signaling pathways were mainly enriched. JAK1 was positively associated with tumor-infiltrating immune cells, and the results of CIBERSORT analysis suggested that JAK1 was correlated with monotypes and M1 macrophages. The results of the TIMER database analysis confirmed that JAK1 was closely associated with the gene markers of M1 macrophages. Thus, JAK1 may serve as a potential prognostic biomarker in LUAD and is associated with immune infiltration.

The determination of a tailored anti-drug antibody (ADA) testing strategy is based on the immunogenicity risk assessment to allow a correlation of ADAs with changes to pharmacokinetics, efficacy, and safety. The clinical impact of ADA formation refines the immunogenicity risk assessment and defines appropriate risk mitigation strategies. Health agencies request for high-risk biotherapeutics to extend ADA monitoring for patients that developed an ADA response to the drug until ADAs return to baseline levels. However, there is no common understanding in which cases an extension of ADA follow-up sampling beyond the end of study (EOS) defined in the clinical study protocol is required. Here, the Immunogenicity Strategy Working Group of the European Immunogenicity Platform (EIP) provides recommendations on requirements for an extension of ADA follow-up sampling in clinical studies where there is a high risk of serious consequences from ADAs. The importance of ADA evaluation during a treatment-free period is recognized but the decision whether to extend ADA monitoring at a predefined EOS should be based on evaluation of ADA data in the context of corresponding clinical signals. If the clinical data set shows that safety consequences are minor, mitigated, or resolved, further ADA monitoring may not be required despite potentially detectable ADAs above baseline. Extended ADA monitoring should be centered on individual patient benefit.

In this paper, we discuss the inference problem about the Box-Cox transformation model when one faces left-truncated and right-censored data, which often occur in studies, for example, involving the cross-sectional sampling scheme. It is well-known that the Box-Cox transformation model includes many commonly used models as special cases such as the proportional hazards model and the additive hazards model. For inference, a Bayesian estimation approach is proposed and in the method, the piecewise function is used to approximate the baseline hazards function. Also the conditional marginal prior, whose marginal part is free of any constraints, is employed to deal with many computational challenges caused by the constraints on the parameters, and a MCMC sampling procedure is developed. A simulation study is conducted to assess the finite sample performance of the proposed method and indicates that it works well for practical situations. We apply the approach to a set of data arising from a retirement center.

Talent development research has uncovered common conditions for nurturing talented individuals: enriched early environment, appropriate instruction, long-term and deliberate practice, singleness of purpose, and centers of excellence. Talent research also reveals that parents play a critical role in arranging and facilitating these conditions and helping their child’s talent to blossom. This article reports six talent-nurturing things parents do according to case-study research by Kiewra and colleagues across various talent domains such as chess, figure skating, baton twirling, violin, writing, and spelling. Parents provide an enriched early environment, arrange for appropriate instruction, facilitate long-term and deliberate practice, support singleness of purpose, gravitate to or establish a center of excellence, and are fully committed and make life-changing sacrifices to nurture their child’s talents.

Summary Background Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first‐line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. Aims To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. Methods This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. Results Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2‐24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine

Aim: To present the reader with different approaches used to compare immunogenicity methods when changes are needed during a clinical program. Results: Five case studies are presented, in the first two case studies, the approach utilized a small sample size for the comparison. In the third case, all samples from a study were analyzed by both methods. In the fourth case, the intended use of noncomparable assays in an integrated summary drove design of experiments to establish the expected limits of pooling data. In the fifth case, a selectivity approach was used as an alternate to use of incurred samples. Conclusion: When data pooling across methods is needed, it is important to define the limits of comparability.

Purpose Advanced non-small-cell lung cancer (aNSCLC; stage IIIB/IV) presents a substantial clinical burden to society; reliable estimates of its economic burden are lacking. Therefore, this study aimed to quantify real-world health care resource utilization (HCRU) and costs of patients with squamous (SQ) and non-SQ (NSQ) aNSCLC who received two or more lines of treatment (2L+) in Europe, and to describe cost-predictors. Methods The LENS (Leading the Evaluation of Non-squamous and Squamous NSCLC) retrospective chart review study collected data from 2L+ patients with aNSCLC diagnosed between 07/2009 and 08/2011 (wave 1) or 07/2010 and 09/2012 (wave 2) in France, Germany, Italy, Spain, England, the Netherlands, and Sweden. Patients were followed from diagnosis through most recent visit/death. A weighted average of country-specific unit costs (2018 Euro) was applied to systemic anti-cancer therapy usage and HCRU (hospital/emergency department visit, surgery, radiotherapy, ancillary care, biomarker testing) to determine the total cost from aNSCLC diagnosis to death. Generalized linear models (gamma distribution, log link) were used to assess clinical and demographic predictors. Results Of 973 2L+ aNSCLC patients, median overall survival (OS) was 1.5 years from advanced diagnosis (range: 0.2-5.3; median OS: 1.4 [SQ], 1.6 [NSQ]), 79.0% died during follow-up. Weighted mean total per-patient costs were €21,273, ranging from €17,761 (England) to €30,854 (Sweden), and €15,446 (SQ) to €26,477 (NSQ). Systemic drug costs comprised 77.4% of total costs. Insurance status, presence of epidermal growth factor receptor (EGFR) mutation, SQ histology, age, alcohol abuse, and year of diagnosis were significant predictors for lower total costs per patient-month, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥1 and country for higher costs. Conclusion In the era pre-immunotherapy, HCRU and costs were substantial in aNSCLC 2L+ patients, with most of the costs accrued prior to start of 2L. NSQ patients incurred significantly higher total costs than SQ patients in all participating countries.

Students are distracted by mobile technology in the classroom when learning from lectures and outside the classroom when studying. Students are susceptible to distractions because they are not fully engaged in learning. In the classroom, they record notes mindlessly that capture just one-third of important lesson ideas. When they study outside the classroom, they study information in a piecemeal fashion and employ mindless repetition strategies. These weak and unengaging learning strategies open the door for digital distractions. One potential means to engage students in meaningful learning and to offset digital distractions is an integrated strategy system called SOAR, which stands for select, organize, associate, and regulate. This chapter describes SOAR and how instructors can maximize SOAR's components to curb digital distractions by improving student note taking in the classroom and study behaviors outside the classroom. The chapter concludes by specifying how instructors can teach students to SOAR on their own.

The gene-gene interaction is known to be the genetic cause of major depressive disorder (MDD). Several genes have been found to be related to MDD. The objectives of this study were to verify the susceptibility genes of MDD in a sample of university students in China, and to investigate possible gene-gene interactions in relation to the risk of MDD.7,627 Chinese Han freshmen were enrolled at baseline survey in 2018. After a 2-year follow-up, 170 new onset MDD cases and 680 controls with DNA samples reserved were sequenced and genotyped for 4 selected Single Nucleotide Polymorphisms (SNPs) in a nested case-control study (ratio of 1:4). Chi-square test was used to identify the relationships between SNPs and risk of MDD. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interactions.The 2-year incidence of MDD in Chinese college students was 3.75% (95% CI: 3.24%, 4.34%). There was no statistical difference in MDD incidences between males (3.74%, 95% CI: 3.12%, 4.49%) and females (3.77%, 95% CI: 2.97%, 4.78%) (p0.05). TMEM161B (rs768705) was positively associated with new onset MDD (χThe results could not be inferred to other ethnics.This study provided evidence that combined rs768705 (TMEM161B) and rs35936514 (LHPP) may modulate the risk of MDD.

Herein, we present hierarchical Mo-doped NiCoP@carbon microspheres that exhibit a noticeable enhancement in catalytic activity and fast kinetics for hydrogen evolution. An overpotential of 74.6 mV at 10 mA cm−2 and 54.9 mV dec−1 can be achieved. These results demonstrated the excellent electrochemical properties arising from the intrinsic characteristics of elemental doping and morphology control. We believe that this work opens a new avenue to fabricating TMD-based catalysts via the engineering of transition metal compounds.

Perovskite oxides have attracted great attention in electrochemistry due to their compositional and structural flexibility. Herein, microwave/ultrasound assisted hydrothermal procedures were developed to synthesize Ce-doped LaCoO

This study explores factors enhancing the likelihood that three demographically disadvantaged groups of selective science high school graduates would complete a university STEM degree 4-6 years later. The target groups are labeled as disadvantaged in terms of STEM pipeline persistence compared to school peers, and include: (1) women, (2) those without a parent in a STEM field, and (3) those whose parents were not educated beyond high school. Employing Social Cognitive Career Theory as a conceptual framework, we focus on two categories of factors. Individual factors incorporate motivation and career intention brought to the high school experience. Environmental factors include graduates' high school experiences related to their STEM interest and capacity development. The individual variables include: STEM career intentions prior to high school, motivation for attending a specialized science high school, and motivation for pursuing advanced science courses in high school. Environmental factors include whether participants partook in an authentic research experience, had a mentor, felt they belonged at the school, maintained their interest in STEM as well as perceived intellectual capacity for STEM throughout high school. The results have promising implications for educational policy associated with STEM talented students.

Peanut (Arachis hypogaea L.) is one of the most important oilseed crops that are cultivated worldwide. Peanut production is now greatly limited by drought stress, which is a major environmental challenge. The urgent task for current peanut research is thus to study the underlying mechanisms of peanut drought tolerance, to identify genes that are closely associated with drought tolerance, and to create new germplasms/varieties with high drought tolerance. In this review, we summarize recent advances in the acclimation mechanisms to water deficiency and the genetic improvement of peanut for drought tolerance, and propose the perspectives for the future peanut research.

Targeted genome engineering refers to technologies that are used for site-specific genome modifications such as knockout, knockin and transcriptional regulation of genes of interest in organisms. Site-specific recombination system, zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) (CRISPR/Cas9) technologies are the representatives of targeted genome engineering and have been widely used in crop basic and applied research. In this review, we introduce the basic information and action modes of these different genome engineering technologies, summarize the recent progresses of targeted genome engineering technologies and their applications in crop improvement, and propose perspectives for genome engineering-mediated modifications of crop plants in the future.

Plant TRANS-ACTING SIRNA3 (TAS3)-derived short interfering RNAs (siRNAs) include tasiR-AUXIN RESPONSE FACTORs (ARFs), which are functionally conserved in targeting ARF genes, and a set of non-tasiR-ARF siRNAs, which have rarely been studied. In this study, TAS3 siRNAs were systematically characterized in rice (Oryza sativa). Small RNA sequencing results showed that an overwhelming majority of TAS3 siRNAs belong to the non-tasiR-ARF group, while tasiR-ARFs occupy a diminutive fraction. Phylogenetic analysis of TAS3 genes across dicot and monocot plants revealed that the siRNA-generating regions were highly conserved in grass species, especially in the Oryzoideae. Target genes were identified for not only tasiR-ARFs but also non-tasiR-ARF siRNAs by analyzing rice Parallel Analysis of RNA Ends datasets, and some of these siRNA–target interactions were experimentally confirmed using tas3 mutants generated by genome editing. Consistent with the de-repression of target genes, phenotypic alterations were observed for mutants in three TAS3 loci in comparison to wild-type rice. The regulatory role of ribosomes in the TAS3 siRNA–target interactions was further revealed by the fact that TAS3 siRNA-mediated target cleavage, in particular tasiR-ARFs targeting ARF2/3/14/15, occurred extensively in rice polysome samples. Altogether, our study sheds light into TAS3 genes in plants and expands our knowledge about rice TAS3 siRNA–target interactions., A population of rice short interfering RNAs derived from TRANS-ACTING SIRNA3 loci direct target mRNA cleavage, revealing a broader role of TRANS-ACTING SIRNA3 genes in rice growth and stress responses.

Background Soil salinization represents a serious threat to global rice production. Although significant research has been conducted to understand salt stress at the genomic, transcriptomic and proteomic levels, few studies have focused on the translatomic responses to this stress. Recent studies have suggested that transcriptional and translational responses to salt stress can often operate independently. Results We sequenced RNA and ribosome-protected fragments (RPFs) from the salt-sensitive rice (O. sativa L.) cultivar ‘Nipponbare’ (NB) and the salt-tolerant cultivar ‘Sea Rice 86’ (SR86) under normal and salt stress conditions. A large discordance between salt-induced transcriptomic and translatomic alterations was found in both cultivars, with more translationally regulated genes being observed in SR86 in comparison to NB. A biased ribosome occupancy, wherein RPF depth gradually increased from the 5′ ends to the 3′ ends of coding regions, was revealed in NB and SR86. This pattern was strengthened by salt stress, particularly in SR86. On the contrary, the strength of ribosome stalling was accelerated in salt-stressed NB but decreased in SR86. Conclusions This study revealed that translational reprogramming represents an important layer of salt stress responses in rice, and the salt-tolerant cultivar SR86 adopts a more flexible translationally adaptive strategy to cope with salt stress compared to the salt susceptible cultivar NB. The differences in translational dynamics between NB and SR86 may derive from their differing levels of ribosome stalling under salt stress.

The rapid development of renewable energy, represented by wind and photovoltaic, provides a new solution for island power supplies. However, due to the intermittent and random nature of renewable energy, a microgrid needs energy-storage components to stabilize its power supply when coupled with them. The emergence of seawater-pumped storage stations provides a new method to offset the shortage of island power supply. In this study, an optimal scheduling of island microgrid is proposed, which uses seawater-pumped storage station as the energy storage equipment to cooperate with wind, photovoltaic and diesel generator. First, a mathematic formulation of seawater-pumped storage station with renewable energy is presented. Then, to reach the goal of economic dispatch, an optimal scheduling model of island microgrid is established with the consideration of both respective operation constraints and island load requirements. Finally, the effectiveness of the proposed model is verified by an island microgrid over two typical seasons. The simulation results show that the proposed framework not only increases the usage of renewable energy, but also improves the operational reliability and economy of island microgrids.

Students are expected to know how to learn but rarely are taught the learning strategies needed for academic success. There is a long history of learning strategy research that has uncovered many effective and independent strategies students can use to facilitate learning and boost achievement. Unfortunately, researchers have been less successful in devising and promoting integrated and uncomplicated study systems students can employ. A prescriptive strategy system, SOAR, combines four simple and empirically proven strategies that can be readily employed by students for various academic tasks. SOAR is an acronym for the system’s four integrated components: Select, Organize, Associate, and Regulate. Briefly, select refers to selecting and noting key lesson ideas. Organize refers to representing selected information using graphic organizers such as matrices and illustrations. Associate refers to connecting selected ideas to one another and to previous knowledge. Regulate refers to monitoring and assessing one’s own learning. SOAR is based on information-processing theory and is supported by research. Five empirical studies have investigated SOAR strategies compared to students’ preferred strategies or to another strategy system (SQ3R) and found SOAR to be more effective for aiding learning and comparative writing. Specific means for how to employ each SOAR strategy are described such as recording longhand notes and revising them for select, creating appropriate graphic organizers for organize, generating examples and using mnemonics for associate, and using distributed retrieval and error analysis for regulation. Although research on SOAR is just emerging as of 2019, it appears an effective and simple means for directing students in how to learn and study.

To enhance the intrinsic activity and the density of active sites of the electrocatalyst for the hydrogen evolution reaction (HER), the microwave-assisted synthesis is adopted to prepare hierarchical Ce-doped MoSe2@CNTs as highly-efficient catalysts for HER in both acidic and alkaline conditions. The well-defined hierarchical nanostructure of Ce-doped MoSe2 on multiple carbon nanotubes (MWCNTs) with few layers of MoSe2 nanostructure. The Ce-MoSe2@CNTs sample with an optimal proportion of Ce:Mo (1:5) exhibits outstanding activity and long-term stability in both acidic and alkaline electrolyte. It shows an overpotential of 108 and 166 mV at 10 mA cm−2 in acidic and alkaline electrolyte, respectively. This study offers a prospective opportunity to design and fabricate the highly-effective catalysts coupling with multiple synergistic effect for efficient electrocatalysts.

There has been a shift in college classrooms from students recording lecture notes using a longhand pencil-paper medium to using laptops. The present study investigated whether note-taking medium (laptop, longhand) influenced note taking and achievement when notes were recorded but not reviewed (note taking’s process function) and when notes were recorded and reviewed (note taking’s product function). One unique aspect of the study was determining how laptop and longhand note taking influence the recording of lecture images in notes and image-related achievement. Note-taking results showed that laptop note takers recorded more notes (idea units and words) and more verbatim lecture strings than did longhand note takers who, in turn, recorded more visual notes (signals and images) than did laptop note takers. Achievement results showed that when taking laptop notes, the process function of note taking was more beneficial than the product function of note taking (i.e., better image-related learning and similar text-related learning). When taking longhand notes, the product function of note taking was more beneficial than the process function of note taking (i.e., better text-related learning and similar image-related learning). Achievement findings suggest that the optimal note-taking medium depends on the nature of the lecture and whether notes are reviewed.