Development of environmental DNA metabarcoding primers for marine mollusks and comparison with published primers.

Monitoring mollusk biodiversity is a great challenge due to their large diversity and broad distribution. Environmental DNA (eDNA) technology is increasingly applied for biodiversity monitoring, but relevant studies on marine mollusks are still limited. Although previous studies have developed several pairs of primers for mollusk eDNA analyses, most of them targeted only a small group of mollusks. In this study, seven primers were designed for the mollusk community and validated and compared with eight pairs of published primers to select the best candidates. After in silico test, MollCOI154 and MollCOI255 primers showed non-specific amplification, and same results were also obtained in published primers (COI204, Sepi, and veneroida). Moll12S100, Moll12S195 and Moll16S primers failed to amplify across all genomic DNA from selected mollusk. Except Moll16S, all developed and two published (unionoida and veneroida) primers were successfully amplified on four eDNA samples from Yangtze River estuary. After annotation of the amplified sequences, MollCOI253 showed higher annotation of the amplification results than the other primers. In conclusion, MollCOI253 had better performance in terms of amplification success and specificity, and can provide technical support for eDNA-based research, which will be beneficial for molluscan biodiversity investigation and conservation.

Scale-reconfigurable miniature ferrofluidic robots for negotiating sharply variable spaces.

Magnetic miniature soft robots have shown great potential for facilitating biomedical applications by minimizing invasiveness and possible physical damage. However, researchers have mainly focused on fixed-size robots, with their active locomotion accessible only when the cross-sectional dimension of these confined spaces is comparable to that of the robot. Here, we realize the scale-reconfigurable miniature ferrofluidic robots (SMFRs) based on ferrofluid droplets and propose a series of control strategies for reconfiguring SMFR's scale and deformation to achieve trans-scale motion control by designing a multiscale magnetic miniature robot actuation (M3RA) system. The results showed that SMFRs, varying from centimeters to a few micrometers, leveraged diverse capabilities, such as locomotion in structured environments, deformation to squeeze through gaps, and even reversible scale reconfiguration for navigating sharply variable spaces. A miniature robot system with these capabilities combined is promising to be applied in future wireless medical robots inside confined regions of the human body.

A Paradigm Shift for Asthma Care.

KEY TAKEAWAYS: Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

Dissecting of the Deterioration in Eating Quality for Erect Panicle (Ep) Type High Yield Japonica Super Rice in Northest China.

Ep type is an important morphological improvement (following dwarf breeding and ideal plant type) that has contributed to breeding super-high yielding, and shows a pleiotropic effect in increasing grain yield and also nitrogen-use efficiency (NUE) in rice. Nevertheless, it remains unclear whether Ep has adverse effects on eating quality and how it affects nitrogen uptake and assimilation. In this study, we developed a pair of near-isogenic lines (NILs) for panicle type (NIL-Ep, NIL-non Ep) in the Liaogeng 5 (LG5) and Akihikari (AKI) backgrounds. Rice plants of the NIL-Ep had higher grain numbers per panicle in the middle to bottom spike positions than plants of the NIL-non Ep. The increased grain number is not only is the key factor leading to increased yield but also is the reason for reduced the eating quality. The content of prolamin and glutelin was significantly higher in NIL-Ep, which resulted in higher hardness and worse viscosity of rice after cooking. In addition, the activity of several essential enzymes catalyzing nitrogen metabolism was higher in the NIL-Ep line grains than in the NIL-non Ep, especially from the mid to late grain filling stage. Based on these results, we conclude that Ep positively regulates grain protein accumulation, primarily through enhancing the activity of enzymes involved in nitrogen assimilation and redistribution during the mid to late grain-filling stage, resulting in excessive accumulation of grain protein and decreased eating quality.

Effects of Jianpi Yiqi method for chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with high morbidity and mortality worldwide. Jianpi Yiqi method (JYM) is a classical Chinese therapy in the treatment of COPD. However, there is no systematic review related to JYM for COPD. In this study, we aim to systematically examine the efficacy and safety for clinical use of JYM. METHODS AND ANALYSIS: We will conduct a comprehensive retrieval in the following electronic databases: PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Service System (SinoMed), and other sources. Two trained reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool, independently. Then the meta-analyses will be conducted by using the RevMan 5.2. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. A sensitivity analysis will be performed to evaluate the stability of the results. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. Finally, the quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether JYM is an effective intervention for patients with COPD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKQYV.

Synthesis, characterization, DNA binding, topoisomerase I inhibition and antiproliferation activities of three new functionalized terpyridine platinum(II) complexes.

Three new platinum(II) complexes with pendent morpholine were synthesized, namely complex 1 ([Pt(L)Cl]CF3SO3), complex 2 ([Pt(L)(NH3)](CF3SO3)2) and complex 3 ([Pt(L)(PPh3)](CF3SO3)2), where L = 4'-[4-(4-morpholinobutyloxy)phenyl]-2,2':6',2″-terpyridine and PPh3 = triphenylphosphine. The detailed molecular structures of complex 3, L and its precursor L' (1,4'-[4-(4-bromobutyloxy)phenyl]-2,2':6',2″-terpyridine) were determined by single crystal X-ray diffraction. An evaluation of in vitro cytotoxicity for both ligand and complexes was performed by methyl thiazolyl tetrazolium (MTT) assay in three cancer cell lines and normal cells as the control, respectively. IC50 values of complexes 1-3 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes were greater than cisplatin. Among them, complex 3 with a leaving group PPh3 was found to be the most efficacious complex against certain cell lines, especially for cisplatin-resistant A549cisR cells. These complexes were found to bind DNA, induce efficient DNA unwinding. Meanwhile, topoisomerase (Topo) I inhibitory activities by three complexes were detected, and a minimum inhibitory concentration of 15 µM of complex 3 was found totally inhibit Topo I activity.

Low Interface Energies Tune the Electrochemical Reversibility of Tin Oxide Composite Nanoframes as Lithium-Ion Battery Anodes.

The conversion reaction of lithia can push up the capacity limit of tin oxide-based anodes. However, the poor reversibility limits the practical applications of lithia in lithium-ion batteries. The latest reports indicate that the reversibility of lithia has been appropriately promoted by compositing tin oxide with transition metals. The underlying mechanism is not revealed. To design better anodes, we studied the nanostructured metal/Li2O interfaces through atomic-scale modeling and proposed a porous nanoframe structure of Mn/Sn binary oxides. The first-principles calculation implied that because of a low interface energy of metal/Li2O, Mn forms smaller particles in lithia than Sn. Ultrafine Mn nanoparticles surround Sn and suppress the coarsening of Sn particles. Such a composite design and the resultant interfaces significantly enhance the reversible Li-ion storage capabilities of tin oxides. The synthesized nanoframes of manganese tin oxides exhibit an initial capacity of 1620.6 mA h g-1 at 0.05 A g-1. Even after 1000 cycles, the nanoframe anode could deliver a capacity of 547.3 mA h g-1 at 2 A g-1. In general, we demonstrated a strategy of nanostructuring interfaces with low interface energy to enhance the Li-ion storage capability of binary tin oxides and revealed the mechanism of property enhancement, which might be applied to analyze other tin oxide composites.

Barriers and Facilitators of Mentoring for Trainees and Early Career Investigators in Rheumatology Research: Current State, Identification of Needs, and Road Map to an Inter-Institutional Adult Rheumatology Mentoring Program.

OBJECTIVE: To determine perceived barriers and facilitators to effective mentoring for early career rheumatology investigators and to develop a framework for an inter-institutional mentoring program. METHODS: Focus groups or interviews with rheumatology fellows, junior faculty, and mentors were conducted, audiorecorded, and transcribed. Content analysis was performed using NVivo software. Themes were grouped into categories (e.g., mentor-mentee relationship, barriers, and facilitators of a productive relationship). Rheumatology fellows and early career investigators were also surveyed nationwide to identify specific needs to be addressed through an inter-institutional mentoring program. RESULTS: Twenty-five individuals participated in focus groups or interviews. Attributes of the ideal mentee-mentor relationship included communication, accessibility, regular meetings, shared interests, aligned goals, and mutual respect. The mentee should be proactive, efficient, engaged, committed, focused, accountable, and respectful of the mentor's time. The mentor should support/promote the mentee, shape the mentee's goals and career plan, address day-to-day questions, provide critical feedback, be available, and have team leadership skills. Barriers included difficulty with career path navigation, gaining independence, internal competition, authorship, time demands, funding, and work-life balance. Facilitators of a successful relationship included having a diverse network of mentors filling different roles, mentor-mentee relationship management, and confidence. Among 187 survey respondents, the primary uses of an inter-institutional mentoring program were career development planning and oversight, goal-setting, and networking. CONCLUSIONS: In this mixed-methods study, tangible factors for optimizing the mentor-mentee relationship were identified and will inform the development of an adult rheumatology inter-institutional mentoring program.

Cause-specific mortality in patients with psoriatic arthritis and rheumatoid arthritis.

Objective: The objective of this study was to examine cause-specific mortality in patients with PsA compared with the general population and compared with patients with RA. Methods: A cohort study was performed using The Health Improvement Network among patients aged 18-89 years with data from 1994 to 2010. PsA and RA were defined by medical codes, and up to 10 unexposed controls were matched on practice and start date within the practice. Cause of death was classified using categories from UK death statistics. Each death was manually reviewed to ensure appropriate classification. Age- and sex-adjusted hazard ratios (HRs) and multivariable adjusted HRs were calculated using competing risks survival regression. Results: Among patients with PsA (8706), RA (41 752) and unexposed controls (81 573), 470, 7004 and 5269 deaths were observed, respectively. The most common causes of death among all patients were cardiovascular disease, followed by malignancy, respiratory deaths and infection. Cause of death was unknown in ∼25%. Among PsA patients, cardiovascular (1.09, 0.91-1.32), respiratory (0.97, 0.79-1.20), malignancy (1.03, 0.86-1.25) and infection deaths (1.05, 0.79-1.39) were not elevated. Among patients with RA, cardiovascular (1.55, 1.44-1.66), respiratory (1.85, 1.72-2.01), malignancy (1.18, 1.08-1.28) and infection deaths (2.21, 2.00-2.44) were significantly elevated compared with population controls. Although less common, suicide deaths were elevated in PsA and RA (HR 3.03 and 2.47, respectively). Conclusion: Overall mortality and cause-specific mortality risk were not elevated among patients with PsA except for suicide deaths. Patients with RA were at increased risk of deaths from cardiovascular, respiratory, cancer and infectious diseases.

Barriers to and Facilitators of a Career as a Physician-Scientist Among Rheumatologists in the US.

OBJECTIVE: To determine perceived barriers to and facilitators of a career in rheumatology research, examine factors leading rheumatologists to leave an academic research career, and solicit ways to best support young physician-scientists. METHODS: A web-based survey was conducted among the domestic American College of Rheumatology (ACR) membership from January through March 2014. Inclusion criteria were ACR membership and an available e-mail address. Non-rheumatologists were excluded. The survey assessed demographics, research participation, barriers to and facilitators of a career in research, reasons for leaving a research career (when applicable), and ways in which the ACR could support junior investigators. Content analysis was used to extract relevant themes. RESULTS: Among 5,448 domestic ACR members, 502 responses were obtained (9.2% response rate). After exclusions (38 incomplete, 2 duplicates, 32 non-rheumatologists), 430 responses were analyzed. Participants included fellows, young investigators, established investigators, mentors, clinicians, and those who previously pursued a research career but have chosen a different career path. Funding and mentoring were the most highly ranked barriers and facilitators. Protection from clinical and administrative duties, institutional support, and personal characteristics such as resilience and persistence were also ranked highly. The most commonly cited reasons for leaving an academic research career were difficulty obtaining funding and lack of department or division support. CONCLUSION: This is the first study to examine barriers to and facilitators of a career in rheumatology research from the perspectives of diverse groups of rheumatologists. Knowledge of such barriers and facilitators may assist in designing interventions to support investigators during vulnerable points in their career development.

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study.

OBJECTIVES: We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors. METHODS: A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use. RESULTS: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73). CONCLUSIONS: Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA.

Validity of psoriatic arthritis and capture of disease modifying antirheumatic drugs in the health improvement network.

PURPOSE: The aims of this study are to examine the validity of diagnostic codes for psoriatic arthritis in The Health Improvement Network (THIN) and to examine the agreement between General Practitioner (GP) report and prescription records for disease modifying antirheumatic drugs (DMARDs). METHODS: Questionnaires were sent to the GPs of 100 randomly selected patients with at least one medical record code for psoriatic arthritis. The positive predictive value (PPV) for a GP confirmed diagnosis was calculated, and alternative algorithms were examined to determine which method resulted in the highest PPV. RESULTS: The PPV for a single code for psoriatic arthritis was 85% (95%CI: 75.8-91.7%). Adding a prescription for a DMARD increased the PPV to 91% but with a substantial loss in sensitivity. Agreement between GPs and prescription data for use of an oral DMARD was 69%. CONCLUSIONS: The diagnosis codes for psoriatic arthritis used in THIN are valid. All prescriptions for DMARDs may not be accounted for in THIN.

An aptamer-based electrochemical biosensor for the detection of Salmonella.

Salmonella is one of the most common causes of food-associated disease. An electrochemical biosensor was developed for Salmonella detection using a Salmonella-specific recognition aptamer. The biosensor was based on a glassy carbon electrode modified with graphene oxide and gold nanoparticles. Then, the aptamer ssDNA sequence could be linked to the electrode. Each assembly step was accompanied by changes to the electrochemical parameters. After incubation of the modified electrode with Salmonella, the electrochemical properties between the electrode and the electrolyte changed accordingly. The electrochemical impedance spectrum was measured to quantify the Salmonella. The results revealed that, when more Salmonella were added to the reaction system, the current between the electrode and electrolyte decreased; in other words, the impendence gradually increased. A detection limit as low as 3 cfu/mL was obtained. This novel method is specific and fast, and it has the potential for real sample detection.