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Non-typhoidal Salmonella serovars, such as Salmonella enterica serovar Typhimurium (STm), are a leading cause of inflammatory diarrhea in otherwise healthy individuals. Among children, the elderly, and immunocompromised individuals, STm can spread to systemic sites and cause potentially lethal bacteremia. Phagocytic cells and the immune complement system are pivotal to preventing the dissemination of STm. PgtE, an STm outer membrane protease, has been previously described to cleave over a dozen mammalian protein substrates in vitro , including complement protein C3. However, these activities have mostly been observed with mutant, avirulent strains with a truncated O-antigen that renders bacteria sensitive to complement killing. Here, we report that virulent STm utilizes PgtE to evade complement-mediated killing in vivo . The wild-type pathogen increases pgtE expression and PgtE proteolytic function within macrophages and in macrophage-like in vitro growth conditions, concomitant with physiologic O-antigen shortening in these environments. Furthermore, we found that wild-type STm's resistance to complement-mediated serum and neutrophil killing is PgtE-dependent. We propose that PgtE promotes the systemic spread of STm by acting as a second line of defense against complement when STm escapes from a macrophage.

Natural carotenoids from microalgae have received more attention as an alternative source. In this study, fulvic acid (FA), a plant growth regulator, was used to enhance carotenoid accumulation in microalgae Dunaliella bardawil rich in lutein. However, the addition of FA promoted pigment synthesis but also exhibited an inhibitory effect on biomass. Therefore, the optimization of culture conditions was performed to further enhance carotenoid accumulation, including high light stress (10,000 lx) and the two-stage cultivation comprising 1-aminocyclopropane-1-carboxylic acid (ACC) and FA. Under both culture conditions, the growth inhibition caused by FA was alleviated, leading to a further increase in the contents of chlorophylls and carotenoids. HPLC analysis revealed that the production of lutein, α-carotene and β-carotene increased by 0.44-, 0.37- and 0.54-fold under the treatment of 400 mg/L FA with high light intensity and 0.91-, 1.15-0.29-fold under the two-stage cultivation comprising 11 mM ACC and 500 mg/L FA. Furthermore, algal cells under FA treatment and the two-stage cultivation stained with Bodipy505/515 emitted stronger fluorescence under a laser confocal microscope, suggesting that lipid accumulation was increased. Additionally, the transcription levels of carotenogenic genes were also found to be up-regulated by qRT-PCR. These results indicated an enhancement in both the storage capacity and synthesis of carotenoids in D. bardawil. This study revealed the potential application of plant growth regulators in promoting carotenoid accumulation in D. bardawil which could be further improved by optimizing the culture conditions, providing a reference for efficient carotenoid production in microalgae., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This paper presents an equivalent source method (ESM) for analyzing sound propagation in small-scale acoustic structures with thermoviscous effects. The formulations that describe the thermal, viscous, and acoustic modes for thermoviscous acoustic problems are introduced. The concept of ESM is then applied to solve these formulations, resulting in an efficient numerical computation and implementation procedure. Based on two different strategies, the obtained ESM formulations are coupled at the boundary using the isothermal, non-slip, and null-divergence conditions. The coupling based on the first strategy is efficient for solving thermoviscous acoustic problems with few matrices required. However, this procedure faces the evaluation of the tangential derivatives of the boundary velocity. Coupling the ESM formulations directly for each component of the total particle velocity at the boundary has no such problem, which leads to the second strategy. However, it entails a larger memory usage compared to the former. Additionally, the coupled finite element method (FEM)-ESM formulations based on the above strategies are developed for acoustic-structural interaction. The validity of the presented ESM formulations is demonstrated through benchmark examples, and that of the coupled FEM-ESM formulation is illustrated by the numerical analysis of a simplified microphone., (© 2024 Acoustical Society of America.)

The study of acoustic radiation from spherical sound sources plays a crucial role in understanding the thermoviscous effects in practical acoustic problems. However, finding a general solution of acoustic radiation from spherical sound sources in thermoviscous fluids remains a formidable challenge. To advance this issue, an analytical method is developed in this paper to calculate the acoustic field radiated by spherical sound sources with the isothermal boundary condition and arbitrary velocity boundary condition. The developed method is utilized to present the solutions of the acoustic field generated by an oscillating sphere and a general spherical sound source, and the accuracy and validity of these solutions are verified through analytical and numerical methods., (© 2024 Acoustical Society of America.)

Systemic lupus erythematosus (SLE) is three times more common and its manifestations are more severe in African American women compared to women of other races. It is not clear whether this is due to genetic differences or factors related to the physical or social environments, differences in health care, or a combination of these factors. Health disparities in patients with SLE between African American patients and persons of other races have been reported since the 1960s and are correlated with measures of lower socioeconomic status. Risk factors for these disparities have been demonstrated, but whether their mitigation improves outcomes for African American patients has not been tested except in self-efficacy. In 2002, the first true US population-based study of patients with SLE with death certificate records was conducted, which demonstrated a wide disparity between the number of African American women and White women dying from SLE. Five years ago, another study showed that SLE mortality rates in the United States had improved but that the African American patient mortality disparity persisted. Between 2014 and 2021, one study demonstrated racism's deleterious effects in patients with SLE. Racism may have been the unmeasured confounder, the proverbial "elephant in the room"-unnamed and unstudied. The etymology of "risk factor" has evolved from environmental risk factors to social determinants to now include structural injustice/structural racism. Racism in the United States has a centuries-long existence and is deeply ingrained in US society, making its detection and resolution difficult. However, racism being man made means Man can choose to change the it. Health disparities in patients with SLE should be addressed by viewing health care as a basic human right. We offer a conceptual framework and goals for both individual and national actions., (© 2024 American College of Rheumatology.)

Dunaliella salina, a microalga that thrives under high-saline conditions, is notable for its high β-carotene content and the absence of a polysaccharide cell wall. These unique characteristics render it a prime candidate as a cellular platform for astaxanthin production. In this study, our initial tests in an E. coli revealed that β-ring-4-dehydrogenase (CBFD) and 4-hydroxy-β-ring-4-dehydrogenase (HBFD) genes from Adonis aestivalis outperformed β-carotene hydroxylase (BCH) and β-carotene ketolase (BKT) from Haematococcus pluvialis counterparts by two-fold in terms of astaxanthin biosynthesis efficiency. Subsequently, we utilized electroporation to integrate either the BKT gene or the CBFD and HBFD genes into the genome of D. salina. In comparison to wild-type D. salina, strains transformed with BKT or CBFD and HBFD exhibited inhibited growth, underwent color changes to shades of red and yellow, and saw a nearly 50% decline in cell density. HPLC analysis confirmed astaxanthin synthesis in engineered D. salina strains, with CBFD + HBFD-D. salina yielding 134.88 ± 9.12 μg/g of dry cell weight (DCW), significantly higher than BKT-D. salina (83.58 ± 2.40 μg/g). This represents the largest amount of astaxanthin extracted from transgenic D. salina, as reported to date. These findings have significant implications, opening up new avenues for the development of specialized D. salina-based microcell factories for efficient astaxanthin production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter ( p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values ( p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased ( p < 0.05) and the peak ratio of P 21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties.

Before age 35, Holman hit over 0.500 at the University of California Los Angeles (UCLA); was recruited by professional baseball; led the Association of Interns and Medical Students and the International Union of Students in Denmark; had his passport confiscated; was stripped of a prestigious internship; shadowed by the Federal Bureau of Investigation ; grilled before a Senate committee on subversive activities; made a major medical discovery; and was recruited to be the new Chief of Medicine at Stanford. Holman was involved in building a leading academic institution. He expanded what medical students and graduates learned and what they researched. Holman saw the collision course between the technological capacity to do more and the growing expectations of the public. Moreover, he anticipated the monetization of health care and how it would widen the gap between what we know and what we practice in health care. He reinvented himself in population health. In contrast to reductionist laboratory-based research, his work embraced complexity and made action researchable and research action-oriented. Some innovations did not survive as originally conceived, but their ethos became mainstream. These included evidence-based management, shared physician-patient decision-making, self-management, critical evaluation of medical technology and diagnostics, and chronic disease management. Through the rise of the twentieth century American biomedical medicine, medical education, and slow-motion health care delivery crises that still occur, Holman changed the debate in a time when the funding, the people, the technology, and the need made all things seem possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Carotenoids are essential for photosynthesis and photoprotection in photosynthetic organisms, which are widely used in food coloring, feed additives, nutraceuticals, cosmetics, and pharmaceuticals. Carotenoid biofortification in crop plants or algae has been considered as a sustainable strategy to improve human nutrition and health. However, the regulatory mechanisms of carotenoid accumulation are still not systematic and particularly scarce in algae. This article focuses on the regulatory mechanisms of carotenoid accumulation in plants and algae through regulatory factors (transcription factors and regulatory proteins), demonstrating the complexity of homeostasis regulation of carotenoids, mainly including transcriptional regulation as the primary mechanism, subsequent post-translational regulation, and cross-linking with other metabolic processes. Different organs of plants and different plant/algal species usually have specific regulatory mechanisms for the biosynthesis, storage, and degradation of carotenoids in response to the environmental and developmental signals. In plants and algae, regulators such as MYB, bHLH, MADS, bZIP, AP2/ERF, WRKY, and orange proteins can be involved in the regulation of carotenoid metabolism. And many more regulators, regulatory networks, and mechanisms need to be explored. Our paper will provide a basis for multitarget or multipathway engineering for carotenoid biofortification in plants and algae.

Health literacy is a crucial factor in determining one's health outcomes. Individuals with high health literacy possess the ability to access, comprehend, evaluate, and utilize health information to maintain, enhance, and advocate for good health. This study aimed to develop and validate a tool called the Health Literacy Questionnaire for Older Adults (HLQ-OA) specifically designed to assess the health literacy of community-dwelling older adults in Taiwan. The development of the HLQ-OA occurred in two phases. Firstly, a systematic literature review was conducted, followed by the evaluation of content validity and face validity through expert and older adult assessments. Subsequently, a cross-sectional study was carried out, involving a convenient sample of 481 older adults from community-dwelling long-term care stations. The final version of the HLQ-OA comprised 16 items that assessed four competencies associated with accessing, understanding, appraising, and applying health-related information. The HLQ-OA demonstrated excellent internal consistency, with an overall Cronbach's α coefficient of 0.94. Additionally, the model fit indices indicated an acceptable fit: RMSEA = 0.046, GFI = 0.909, CFI = 0.945, TLI = 0.939. Furthermore, a high correlation was observed between the HLQ-OA and the HL-SF12 (r = 0.832). These findings support the reliability and validity of the HLQ-OA as a tool for assessing the health literacy of older adults. In conclusion, the HLQ-OA is a reliable and valid instrument that can be effectively utilized to measure the health literacy levels of older adults., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study was undertaken to examine the relationship between alcohol consumption and hip osteoarthritis in women. Alcohol has been associated with both adverse and beneficial health effects generally; however, the relationship between alcohol consumption and hip osteoarthritis has been minimally studied., Methods: Among women in the Nurses' Health Study cohort in the US, alcohol consumption was assessed every 4 years, starting in 1980. Intake was computed as cumulative averages and simple updates with latency periods of 0-4 through 20-24 years. We followed 83,383 women without diagnosed osteoarthritis in 1988 to June 2012. We identified 1,796 cases of total hip replacement due to hip osteoarthritis defined by self-report of osteoarthritis with hip replacement., Results: Alcohol consumption was positively associated with hip osteoarthritis risk. Compared with nondrinkers, multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were HR 1.04 (95% CI 0.90, 1.19) for drinkers of >0 to <5 grams/day, HR 1.12 (95% CI 0.94, 1.33) for 5 to <10 grams/day, HR 1.31 (95% CI 1.10, 1.56) for 10 to <20 grams/day, and HR 1.34 (95% CI 1.09, 1.64) for ≥20 grams/day (P for trend < 0.0001). This association held in latency analyses of up to 16-20 years, and for alcohol consumption between 35-40 years of age. Independent of other alcoholic beverages, the multivariable HRs (per 10 grams of alcohol) were similar for individual types of alcohol intake (wine, liquor, and beer; P = 0.57 for heterogeneity among alcohol types)., Conclusion: Higher alcohol consumption was associated with greater incidence of total hip replacement due to hip osteoarthritis in a dose-dependent manner in women., (© 2023 American College of Rheumatology.)

Phytoene synthase (PSY) is a key enzyme in carotenoid metabolism and often regulated by orange protein. However, few studies have focused on the functional differentiation of the two PSYs and their regulation by protein interaction in the β-carotene-accumulating Dunaliella salina CCAP 19/18. In this study, we confirmed that DsPSY1 from D. salina possessed high PSY catalytic activity, whereas DsPSY2 almost had no activity. Two amino acid residues at positions 144 and 285 responsible for substrate binding were associated with the functional variance between DsPSY1 and DsPSY2. Moreover, orange protein from D. salina (DsOR) could interact with DsPSY1/2. DbPSY from Dunaliella sp. FACHB-847 also had high PSY activity, but DbOR could not interact with DbPSY, which might be one reason why it could not highly accumulate β-carotene. Overexpression of DsOR , especially the mutant DsOR His , could significantly improve the single-cell carotenoid content and change cell morphology (with larger cell size, bigger plastoglobuli, and fragmented starch granules) of D. salina . Overall, DsPSY1 played a dominant role in carotenoid biosynthesis in D. salina , and DsOR promoted carotenoid accumulation, especially β-carotene via interacting with DsPSY1/2 and regulating the plastid development. Our study provides a new clue for the regulatory mechanism of carotenoid metabolism in Dunaliella . IMPORTANCE Phytoene synthase (PSY) as the key rate-limiting enzyme in carotenoid metabolism can be regulated by various regulators and factors. We found that DsPSY1 played a dominant role in carotenogenesis in the β-carotene-accumulating Dunaliella salina , and two amino acid residues critical in the substrate binding were associated with the functional variance between DsPSY1 and DsPSY2. Orange protein from D. salina (DsOR) can promote carotenoid accumulation via interacting with DsPSY1/2 and regulating the plastid development, which provides new insights into the molecular mechanism of massive accumulation of β-carotene in D. salina ., Competing Interests: The authors declare no conflict of interest.

Background: The CSP590 randomized trial was designed to estimate the effect of lithium on suicidality. After a third of the intended number of participants were enrolled, the hazard ratio of suicidality was 1.10 (95% CI: 0.77, 1.55). Based on this, the trial was stopped for futility. However, only 17% of patients adhered to the specified protocol., Aims: The objective was to estimate the per-protocol effect of lithium on suicidality, that is, the effect of adhering to the treatment strategies as specified in the protocol., Methods: We stopped individuals' follow-up if/when they showed evidence of nonadherence. We then conducted the analysis in the restricted sample, adjusting for prognostic factors that predict adherence via inverse probability weighting. The primary outcome was the 12-month risk of suicidality (including death from suicide, suicide attempt, interrupted attempt, hospitalization specifically to prevent suicide)., Results: The estimated 12-month risk of suicidality was 18.8% for lithium, and 24.3% for placebo. The risk ratio was 0.78 (95% CI: 0.43, 1.37) and the risk difference -5.5 percentage points (95% CI: -17.5, 5.5). Results were consistent across sensitivity analyses., Conclusions: With one-third of the targeted sample size, lithium effects (compared with placebo) ranging between a 17.5% reduction and a 5.5% increase in the risk of suicidality were highly compatible with the data. Thus, a protective effect of lithium on suicidality among patients with bipolar disorder or major depressive disorder cannot be ruled out. Trials should incorporate adequate per-protocol analyses into the decision-making processes for stopping trials for futility.

MADS transcription factors are involved in the regulation of fruit development and carotenoid metabolism in plants. However, whether and how carotenoid accumulation is regulated by algal MADS are largely unknown. In this study, we first used functional complementation to confirm the functional activity of phytoene synthase from the lutein-rich Dunaliella sp. FACHB-847 (DbPSY), the key rate-limiting enzyme in the carotenoid biosynthesis. Promoters of DbPSY and DbLcyB (lycopene β-cyclase) possessed multiple cis-acting elements such as light-, UV-B-, dehydration-, anaerobic-, and salt-responsive elements, W-box, and C-A-rich-G-box (MADS-box). Meanwhile, we isolated one nucleus-localized MADS transcription factor (DbMADS), belonging to type I MADS gene. Three carotenogenic genes, DbPSY, DbLcyB, and DbBCH (β-carotene hydroxylase) genes were upregulated at later stages, which was well correlated with the carotenoid accumulation. In contrast, DbMADS gene was highly expressed at lag phase with low carotenoid accumulation. Yeast one-hybrid assay and dual-luciferase reporter assay demonstrated that DbMADS could directly bind to the promoters of two carotenogenic genes, DbPSY and DbLcyB, and repress their transcriptions. This study suggested that DbMADS may act as a negative regulator of carotenoid biosynthesis by repressing DbPSY and DbLcyB at the lag phase, which provide new insights into the regulatory mechanisms of carotenoid metabolism in Dunaliella., (© 2023 Wiley Periodicals LLC.)

Dunaliella salina is the most salt-tolerant eukaryote and has the highest β-carotene content, but its carotenoid synthesis pathway is still unclear, especially the synthesis of lycopene, the upstream product of β-carotene. In this study, DsGGPS , DsPSY , DsPDS , DsZISO , DsZDS , DsCRTISO , and DsLYCB genes were cloned from D. salina and expressed in Escherichia coli. A series of carotenoid engineering E. coli strains from phytoene to β-carotene were obtained. ZISO was first identified from Chlorophyta , while CRTISO was first isolated from algae. It was found that DsZISO and DsCRTISO were essential for isomerization of carotenoids in photosynthetic organisms and could not be replaced by photoisomerization, unlike some plants. DsZDS was found to have weak beta cyclization abilities, and DsLYCB was able to catalyze 7,7',9,9'-tetra- cis -lycopene to generate 7,7',9,9'-tetra- cis -β-carotene, which had not been reported before. A new carotenoid 7,7',9,9'-tetra- cis -β-carotene, the beta cyclization product of prolycopene, was discovered. Compared with the bacterial-derived carotenoid synthesis pathway, there is higher specificity and greater efficiency of the carotenoid synthesis pathway in algae. This research experimentally confirmed that the conversion of phytoene to lycopene in D. salina was similar to that of plants and different from bacteria and provided a new possibility for the metabolic engineering of β-carotene. IMPORTANCE The synthesis mode of all trans -lycopene in bacteria and plants is clear, but there are still doubts in microalgae. Dunaliella is the organism with the highest β-carotene content, and plant-type and bacterial-type enzyme genes have been found in its carotenoid metabolism pathway. In this study, the entire plant-type enzyme gene was completely cloned into Escherichia coli, and high-efficiency expression was obtained, which proved that carotenoid synthesis of algae is similar to that of plants. In bacteria, CRT can directly catalyze 4-step continuous dehydrogenation to produce all trans -lycopene. In plants, four enzymes (PDS, ZISO, ZDS, and CRTISO) are involved in this process. Although a carotenoid synthetase similar to that of bacteria has been found in algae, it does not play a major role. This research reveals the evolutionary relationship of carotenoid metabolism in bacteria, algae, and plants and is of methodologically innovative significance for molecular evolution research.

Polymyxin A1 was a rarely investigated member in the polymyxins family produced by Bacillus aerosporus . As a cyclic non-ribosomal lipopeptide, it was purified from Paenibacillus thiaminolyticus for the first time. The producing strain SY20 was screened from Chinese natural fermented bamboo shoots and identified as P. thiaminolyticus SY20 using 16S rRNA homology along with whole genome sequencing. The optimum incubation time was 32 h by the growth kinetics of antimicrobial agent production. The proteinaceous nature of antimicrobial agents was characterized according to the physicochemical properties of the cell-free supernatant. Subsequently, the active antimicrobial agent was purified from the supernatant using ammonium sulfate-graded precipitation, ion-exchange chromatography, and C 18 -H chromatography. The active agent was identified as polymyxin A1 with a molecular weight 1156.7 Da and antimicrobial activity mainly against Gram-negative bacteria. The molecular structure, a cyclic heptapeptide and a tripeptide side chain acylated by a fatty acid at the amino terminus, was elucidated using the combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), amino acid analysis, and whole genome mining tool. Meanwhile, the biosynthetic gene cluster of polymyxin A1 including five open reading frames (ORFs) was demonstrated in the genome. The compound should be further explored for its efficacy and toxicity in vivo to develop its application., 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 Wu, Liu, Liang, Huang, Lin and Xiao.)

Microalgae are considered to be a very promising class of raw material for carotenoid production. In this study, melatonin (MLT), a widely used plant growth regulator, was added to the autotrophic medium of Dunaliella bardawil to explore its effects on the growth and pigment accumulation of Dunaliella bardawil. The results showed that the induction of exogenous MLT alone was not beneficial to the growth and pigment accumulation of Dunaliella bardawil, and the higher the concentration, the more obvious the inhibitory effect on the algal cells. Therefore, a strategy to promote carotenoid accumulation in Dunaliella bardawil by combining exogenous MLT and light induction was carried out. Under 4500 LUX light intensity, the content of zeaxanthin was significantly increased under exogenous MLT induction. In the 200 μg/mL, 300 μg/mL, and 400 μg/mL MLT-treated groups, the zeaxanthin single-cell content in the 300 μg/mL-treated group was as high as 0.38 ng/mL (0.17 ng/mL in the control group), which was 1.24-fold higher compared to the control. Under 9500 LUX light intensity, all carotenoids showed an increasing trend in all experimental groups, except for zeaxanthin, which showed a decreasing trend. The effect of 300 μg/mL showed the most obvious in the 200 μg/mL,300 μg/mL, and 400 μg/mL MLT treatment groups, where the lutein, α-carotene and β-carotene contents were 1.24, 1.14 and 1.31 times higher than those of the control group, respectively. Overall, exogenous MLT at high light intensities had a significant effect on pigment accumulation in Dunaliella bardawil., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As one of the sources of biodiesel, microalgae are expected to solve petroleum shortage. In this study, different concentrations of piperonyl butoxide were added to the culture medium to investigate their effects on the growth, pigment content, lipid accumulation, and content of carotenoids in Dunaliella tertiolecta . The results showed that piperonyl butoxide addition significantly decreased the biomass, chlorophyll content, and total carotenoid content but hugely increased the lipid accumulation. With the treatment of 150 ppm piperonyl butoxide combined with 8000 Lux light intensity, the final lipid accumulation and single-cell lipid content were further increased by 21.79 and 76.42% compared to those of the control, respectively. The lipid accumulation in D. tertiolecta is probably related to the increased expression of DtMFPα in D. tertiolecta under the action of piperonyl butoxide. The phylogenetic trees of D. tertiolecta and other oil-rich plants were constructed by multiple sequence alignment of DtMFPα , demonstrating their evolutionary relationship, and the tertiary structure of DtMFPα was predicted. In conclusion, piperonyl butoxide has a significant effect on lipid accumulation in D. tertiolecta , which provides valuable insights into chemical inducers to enhance biodiesel production in microalgae to solve the problem of diesel shortage.

Chronic myeloid leukemia (CML) is a malignant disease of the hematopoietic system with crucial pathogenic protein named BCR-ABL, which endangers the life of patients severely. As a milestone of targeted drug, Imatinib has achieved great success in the treatment of CML. Nevertheless, inevitable drug resistance of Imatinib has occurred frequently in clinical due to the several mutations in the BCR-ABL kinase. Subsequently, the second-generation of tyrosine kinase inhibitors (TKIs) against BCR-ABL was developed to address the mutants of Imatinib resistance, except T315I. To date, the third-generation of TKIs targeting T315I has been developed for improving the selectivity and safety. Notably, the first allosteric inhibitor has been in market which could overcome the mutations in ATP binding site effectively. Meanwhile, some advanced technology, such as proteolysis-targeting chimeras (PROTAC) based on different E3 ligand, are highly expected to overcome the drug resistance by selectively degrading the targeted proteins. In this review, we summarized the current research progress of inhibitors and degraders targeting BCR-ABL for the treatment of CML., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Cold stress is one of the abiotic stress conditions that severely limit plant growth and development and productivity. Triacylglycerol lipases are important metabolic enzymes for the catabolism of triacylglycerols and, therefore, play important roles in cellular activities including seed germination and early seedling establishment. However, whether they play a role in cold stress responses remains unknown. In this study, we characterized two Arabidopsis triacylglycerol lipases, MPL1 and LIP1 and defined their role in cold stress. The expression of MPL1 and LIP1 is reduced by cold stress, suggesting that they may be negative factors related to cold stress. Indeed, we found that loss-of-function of MPL1 and LIP1 resulted in increased cold tolerance and that the mpl1lip1 double mutant displayed an additive effect on cold tolerance. We performed RNA-seq analysis to reveal the global effect of the mpl1 and lip1 mutations on gene expression under cold stress. The mpl1 mutation had a small effect on gene expression under both under control and cold stress conditions whereas the lip1 mutation caused a much stronger effect on gene expression under control and cold stress conditions. The mpl1lip1 double mutant had a moderate effect on gene expression under control and cold stress conditions. Together, our results indicate that MPL1 and LIP1 triacylglycerol lipases are negative regulators of cold tolerance without any side effects on growth in Arabidopsis and that they might be ideal candidates for breeding cold-tolerant crops through genome editing technology.

Dunaliella salina can accumulate a large amount of β-carotene which is generally considered to be its terminal product of carotenoid metabolism. In this study, it was proved that D. salina has the ketolase (DsBKT) of catalyzing the synthesis of astaxanthin, the downstream products of β-carotene. Therefore, the reason why D. salina does not synthesize astaxanthin is the purpose of this study. The enzymatic activity of DsBKT was detected by functional complementation assays in Escherichia coli, results showed that DsBKT had efficient ketolase activity toward β-carotene and zeaxanthin to produce astaxanthin, indicating that there were complete astaxanthin-producing genes in Dunaliella. Unlike the induced expression of Lycopene cyclase (catalyzing β-carotene synthesis) under salt stress, the expression of DsBKT was very low under both normal and stress conditions, which may be the main reason why D. salina cannot accumulate astaxanthin. On the contrary, with the astaxanthin-rich Haematococcus pluvialis as a control, its BKT gene was significantly upregulated under salt stress. Further study showed that DsBKT promoter had strong promoter ability and could stably drive the expression of ble-egfp in D. salina. Obviously, DsBKT promoter is not the reason of DsBKT not being expressed which may be caused by Noncoding RNA., (© 2021 Wiley Periodicals LLC.)

Previous studies have found that probiotic supplements can ameliorate mental behavioral disorders. This study investigated the effects of Lactiplantibacillus plantarum DMDL 9010 (LP9010) intake on the depression-like behavior induced by dextran sodium sulfate (DSS) and its possible mechanism. Male C57BL/6N mice were fed with DSS to establish the model of ulcerative colitis. LP9010 intake reduced the DSS-induced inflammatory response, and repaired intestinal barrier damage, as well as lightened depression-like behavior. LP9010 supplementation also inhibited neuroinflammation by up-regulating the levels of neurotransmitters, especially 5-HT, NE, DA, and 5-HIAA. Moreover, the intake of LP9010 reorganized the gut microbiome by increasing the relative abundance of Bacteroidetes and Firmicutes, and decreasing the relative abundance of Proteobacteria and Verrucomicrobia. Furthermore, treatment with LP9010 increased the levels of short-chain fatty acids, such as butyric acid and propionic acid. In conclusion, LP9010 intake was a promising probiotic intervention strategy for the prevention of colitis-induced behavioral disorders through the microbiota-gut-brain axis.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression., Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event., Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019., Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo., Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide., Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group., Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities., Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Dunaliella bardawil, a unicellular green alga, can accumulate a large amount of lutein and β-carotene under stresses. Using chemical inducers combined with abiotic stress to promote the accumulation of high value-added products such as lipids and carotenoids in microalgae has attracted more and more attention. In this study, creatinine was added into autotrophic medium to investigate its effects on the growth, chlorophyll content, and the ingredients and content of carotenoids in D. bardawil. The results showed that creatinine alone could significantly increase the biomass, chlorophyll and carotenoid contents of D. bardawil, among which the contents of lutein and β-carotene were further increased, while the content of zeaxanthin was decreased. In order to further improve the content of the two carotenoids, different light intensities combined with creatinine have been adopted. Under 6.589 W/m 2 light intensity, creatinine could effectively increase the production of lutein, zeaxanthin, α-carotene and β-carotene. Compared with the control, the content of lutein increased by 46 % and the content of β-carotene increased by 77 % when the concentration of creatinine was 500 μg/mL. In conclusion, creatinine can effectively improve the production lutein and β-carotene in D. bardawil, which is more conducive under lower light intensity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Carotenoids are important precursors of a wide range of apocarotenoids with their functions including: hormones, pigments, retinoids, volatiles, and signals, which can be used in the food, flavors, fragrances, cosmetics, and pharmaceutical industries. This article focuses on the formation of these multifaceted apocarotenoids and their diverse biological roles in all living systems. Carotenoid degradation pathways include: enzymatic oxidation by specific carotenoid cleavage oxygenases (CCOs) or nonspecific enzymes such as lipoxygenases and peroxidases and non-enzymatic oxidation by reactive oxygen species. Recent advances in the regulation of carotenoid cleavage genes and the biotechnological production of multiple apocarotenoids are also covered. It is suggested that different developmental stages and environmental stresses can influence both the expression of carotenoid cleavage genes and the formation of apocarotenoids at multiple levels of regulation including: transcriptional, transcription factors, posttranscriptional, posttranslational, and epigenetic modification. Regarding the biotechnological production of apocarotenoids especially: crocins, retinoids, and ionones, enzymatic biocatalysis and metabolically engineered microorganisms have been a promising alternative route. New substrates, carotenoid cleavage enzymes, biosynthetic pathways for apocarotenoids, and new biological functions of apocarotenoids will be discussed with the improvement of our understanding of apocarotenoid biology, biochemistry, function, and formation from different organisms.

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America., (© 2020 American Academy of Neurology.)

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Community onset K. pneumoniae bacteremia (KPB) is a major problem in Taiwan for decades. We aimed to revisit the role of virulent genotype K1/K2 and possible predisposing factors, compared to our published 2007 cohort., Methods: All adult patients with monomicrobial KPB during 2017 at a medical center in Taiwan were prospectively enrolled. We genotyped the major K types of K. pneumoniae strains, and analyzed the role of prior use of antibiotic or proton pump inhibitor (PPI)., Results: A total of 213 cases were enrolled. Compared to our previous 2007 study (n = 231), there was a higher percentage of patients with community onset bacteremia (75% vs. 60%, p = 0.003). The overall mortality rate was lower in 2017 (23% vs. 32%, p = 0.02), while the rates of antimicrobial resistance (all classes) were higher in 2017. There were 40 cases of liver abscesses in 2017 (19%), with an overall mortality rate of 7.5%. The prevalence of K1 was similar (16% in 2017 vs. 19% in 2007), but the prevalence of K2 decreased significantly (7% in 2017 vs. 17% in 2007, p = 0.001). After excluding 39 cases without data of recent medication use, 48 of 174 (28%) of patients had received a PPI within 90 days. Patients with recent PPI use had more complicated underlying illnesses, higher antimicrobial resistance, and higher in-hospital mortality, but was negatively associated with liver abscess (4% vs. 24%, p = 0.002). Of patients with community-acquired bacteremia, 51% used antibiotics within 90 days. After excluding 37 patients received antibiotics within 14 days before the detection of bacteremia, patient with antibiotic use within 15-90 days had higher Pittsburgh bacteremia scores (4.5 vs. 2.7, p = 0.04), creatinine levels, and frequency of recent surgery, but was not associated with liver abscess (21% vs. 31%, p = 0.33)., Discussion: In summary, after a decade, community onset KPB is still prevalent (1.3 case per 1000 emergency department visit). K1 remains to be the dominant genotype. The association of prior ampicillin/amoxicillin or PPIs use for liver abscess is not confirmed., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Biological remediation of toxic oxygen-containing anions such as nitrate that are common in the environment is of great significance. Therefore, it is necessary to understand the specific role of nitrate and nitrite reductase in the bioremediation process. Bacillus cereus LJ01, which was isolated from traditional Chinese soybean paste, effectively degraded nitrite (such as NaNO 2 ) at 0-15 mmol L -1 in LB medium. Moreover, the nitrite-degrading active substance (ASDN) was isolated and purified from B. cereus LJ01. The nitrite-degrading activity of nitrite reductase (named LJ01-NiR) was 4004.89 U mg -1 . The gene encoding the assimilation of nitrite reductase in B. cereus LJ01 was cloned and overexpressed in E. coli. The purified recombinant LJ01-NiR has a wide range of activities under temperature (20-60 °C), pH (6.5-8.0) and metal ions (Fe 3+ , Fe 2+ , Cu 2+ , Mn 2+ , and Al 3+ ). Kinetic parameters of LJ01-NiR, including the values of K m and V max were 1.38 mM and 2.00 μmol g -1 min -1 , respectively. The results showed that LJ01-NiR could degrade nitrite with or without an electron donor. In addition, sequence analysis revealed that LJ01-NiR was a ferredoxin-dependent nitrite reductase given the presence of conserved [Fe4-S4] cluster and heme-binding domain. The nitrite ion binds to the LJ01-NiR active site by forming three hydrogen bonds with the residues ASN72, ALA133 and ASN140. Due to its high nitrite-degrading activity, LJ01-NiR could potentially be used for environmental pollution treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Lactarius volemus Fr. has been regarded as a great edible medicinal fungal resource in China. In this study, L. volemus Fr. polysaccharide (LVP) with an average molecular weight of 16.842 kDa was obtained by water extraction. The structure of LVP was characterized to be mannan, and the linkages in the mannan were found to comprise the Man p , (1→4)-α-Man and (1→4,6)-α-Man. Furthermore, intraperitoneal administration of LVP increased the thymus, spleen and liver indices, dose-dependently. Additionally, LVP enhanced the immune response and the phagocytic activities. Pathological evaluations showed that LVP in mice increased the proliferation of red medullary lymphocytes (60-70%). Collectively, these results indicated that LVP might be a potential resource of raw material for further investigations of functional foods., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The salt-tolerant unicellular alga Dunaliella bardawil FACHB-847 can accumulate large amounts of lutein, but the underlying cause of massive accumulation of lutein is still unknown. In this study, genes encoding two types of carotene hydroxylases, i.e. , β-carotene hydroxylase (DbBCH) and cytochrome P450 carotenoid hydroxylase (DbCYP97s; DbCYP97A, DbCYP97B, and DbCYP97C), were cloned from D. bardawil . Their substrate specificities and enzyme activities were tested through functional complementation assays in Escherichia coli . It was showed that DbBCH could catalyze the hydroxylation of the β-rings of both β- and α-carotene, and displayed a low level of ε-hydroxylase. Unlike CYP97A from higher plants, DbCYP97A could not hydroxylate β-carotene. DbCYP97A and DbCYP97C showed high hydroxylase activity toward the β-ring and ε-ring of α-carotene, respectively. DbCYP97B displayed minor activity toward the β-ring of α-carotene. The high accumulation of lutein in D. bardawil may be due to the multiple pathways for lutein biosynthesis generated from α-carotene with zeinoxanthin or α-cryptoxanthin as intermediates by DbBCH and DbCYP97s. Taken together, this study provides insights for understanding the underlying reason for high production of lutein in the halophilic green alga D. bardawil FACHB-847.

The halophilic green alga Dunaliella bardawil has been used for commercial production of natural β-carotene by large-scale outdoor cultivation, which often suffers from heat stress especially at noon in hot summers. In this study, the effects of heat stress on cell growth, pigment contents, and activities of antioxidant system in D. bardawil were studied, and RNA-seq experiment was conducted to analyze the transcriptional response to heat stress (42 °C for 2 h) in D. bardawil. High temperature (42 °C) for short time treatment (≤3 h) did not severely affect the cell growth and pigment accumulation of D. bardawil. Multiple genes encoding heat shock proteins for protein folding and antioxidant enzymes against toxic reactive oxygen species were substantially up-regulated significantly under heat stress. D. bardawil cells tended to shift from aerobic to glycolytic metabolism for energy production to increase survival chances under heat stress. Furthermore, the enrichment of ascorbate-glutathione cycle, up-regulation of genes responsible for chloroplast membranes, and changes in lipid characteristics like carbon chain length and unsaturation degree could play a vital role in achieving thermotolerance of D. bardawil. Taken together, this study improved our understanding of the molecular mechanisms of heat stress responses in D. bardawil., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microalgae are unicellular organisms that act as the crucial primary producers all over the world, typically found in marine and freshwater environments. Most of them can live photo-autotrophically, reproduce rapidly, and accumulate biomass in a short period efficiently. To adapt to the uninterrupted change of the environment, they evolve and differentiate continuously. As a result, some of them evolve special abilities such as toleration of extreme environment, generation of sophisticated structure to adapt to the environment, and avoid predators. Microalgae are believed to be promising bioreactors because of their high lipid and pigment contents. Genetic engineering technologies have given revolutions in the microalgal industry, which decoded the secrets of microalgal genes, express recombinant genes in microalgal genomes, and largely soar the accumulation of interested components in transgenic microalgae. However, owing to several obstructions, the industry of transgenic microalgae is still immature. Here, we provide an overview to emphasize the advantage and imperfection of the existing transgenic microalgal bioreactors.

The halophilic green alga Dunaliella bardawil FACHB-847 is rich in lutein and α-carotene, which has great potential for carotenoid production in open ponds. In this study, genes encoding lycopene β- and ε-cyclases (DbLcyB and DbLcyE) from D. bardawil FACHB-847 were functionally identified by genetic complementation in E. coli. The bifunctional DbLcyB not only catalyzed the formation of both mono- and bi-cyclic β-rings with a major β-cyclase activity, but also possessed a weak ε-cyclase activity. In contrast, DbLcyE preferred to convert lycopene into monocyclic δ-carotene, and possessed a weak β-monocyclase activity. Lutein and α-carotene were the prominent carotenoids in D. bardawil FACHB-847, which was in agreement with the result of genetic complementation of co-expression of DbLcyB and DbLcyE in E. coli with α-carotene as the prominent product. The bifunctional DbLcyB and DbLcyE may contribute to the high accumulation of α-carotene in D. bardawil FACHB-847. Interestingly, the accumulation of lutein in D. bardawil FACHB-847 was more sensitive to salt stress, while the accumulation of β-carotene in D. salina CCAP 19/18 was induced by salt stress. In brief, the production of different carotenoid compositions from these two Dunaliella species can be induced by different growth conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glycerol-3-phosphate (G3P) is the important precursors for triacylglycerol synthesis, while glycerol-3-phosphate dehydrogenase (GPDH) determines the formation of G3P. In this study, two GDPH genes, Dtgdp1 and Dtgdp2 were isolated and identified from Dunaliella tertiolecta. The full-length Dtgdp1 and Dtgdp2 CDS were 2016 bp and 2094 bp, which encoded two putative protein sequences of 671 and 697 amino acids with predicted molecular weights of 73.64 kDa and 76.73 kDa, respectively. DtGDP1 and DtGDP2 both had a close relationship with those of algal and higher plants. DtGDP1 shared two conserved superfamily (A1 and A2) and four signature motifs (I-IV), and the DtGDP2 showed six signature domains (from motif I to VI) and DAO&#95;C conserved family. Our previous work showed that the triethylamine intervention could greatly increase the triacylglycerol content (up to 80%) of D. tertiolecta. This study aims to investigate the effect of triethylamine on GPDH expression. Results showed that, when treated by triethylamine at 100 ppm and 150 ppm, the expression levels of Dtgdp1 and Dtgpd2 were increased to 5.121- and 56.964-fold compared with the control, respectively. Triethylamine seemed to enhance lipid metabolic flow by inducing the expressions of Dtgdp1 and Dtgdp2 to increase the lipid content, which provides a new insight into the desired pathway of lipid synthesis in algae through genetic engineering., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A two-step strategy was employed to culture Dunaliella tertiolecta, an oleaginous unicellular green alga, combined by the salt stress and sodium azide intervention, to observe their effects on its lipid accumulation. When the algae cultured at different salt concentrations reached the logarithmic growth phase, sodium azide was added. The results showed that the addition of sodium azide significantly increased the lipid content and had no significant effect on cell biomass. The lipid yield and single cell lipid content under 50 μM sodium azide increased by 10.4% and 21.7%. Under the two-step culture condition, combining of the treatment of 50 μM sodium azide and 2.5 M salt stress, the total lipid productivity and single-cell lipid content were 10% and 70.5% higher than that of the control. It seemed that sodium azide and salinity might have a synergistic effect on the lipid accumulation of D. tertiolecta. It can be concluded that sodium azide is an effective inducer of lipid accumulation in D. tertiolecta, and two-stage cultivation is a feasible way to improve lipid accumulation in microalgae., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of the study was to describe the research environment of scientists in health services and policy research in China., Study Design: Study was conducted during the 2016 Westlake Youth Forum with grantees of China Medical Board and key informants. Mixed methods used anonymous, survey of grantees, semistructured open-ended interviews with randomly selected awardees, convenience samples of extramural reviewers, and senior scientists with research experience in China., Results: Among 51 awardees, 34 responded fully. Fifty percent were women, averaged 42 years; 88% had PhD/MD and 10 years from their advanced degree. Most had overseas research training (94%); 32% held overseas degrees. Their mean salary, $24,000, barely qualifying as middle class in China. Their confidence using analytical techniques were variable. Their interaction with those using their work seemed nascent. Interviewees echo young researchers elsewhere: lack of mentors, statistical consultation, collaborators, and help to run the gauntlet of requirements in doing research., Conclusion: China's health has improved dramatically since 1949. As the ecology of disease change, expectations increase, and services grow, the expertise to evaluate and improve health care needs to expand. This requires recognition of their importance and a concerted effort to recruit, nurture, and sustain this cadre., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microalgae are promising alternatives for sustainable biodiesel production. Previously, it was found that 100 ppm triethylamine greatly enhanced lipid production and lipid content per cell of Dunaliella tertiolecta by 20% and 80%, respectively. However, triethylamine notably reduced biomass production and pigment contents. In this study, a two-stage cultivation with glycerol and triethylamine was attempted to improve cell biomass and lipid accumulation. At the first stage with 1.0 g/liter glycerol addition, D. tertiolecta cells reached the late log phase in a shorter time due to rapid cell growth, leading to the highest cell biomass (1.296 g/liter) for 16 days. However, the increased glycerol concentrations with glycerol addition decreased the lipid content. At the second-stage cultivation with 100 ppm triethylamine, the highest lipid concentration and lipid weight content were 383.60 mg/liter and 37.7% of dry cell weight (DCW), respectively, in the presence of 1.0 g/liter glycerol, which were 27.36% and 72.51% higher than those of the control group, respectively. Besides, the addition of glycerol alleviated the inhibitory effect of triethylamine on cell morphology, algal growth, and pigment accumulation in D. tertiolecta The results indicated that two-stage cultivation is a viable way to improve lipid yield in microalgae. IMPORTANCE Microalgae are promising alternatives for sustainable biodiesel production. Two-stage cultivation with glycerol and triethylamine enhanced the lipid productivity of Dunaliella tertiolecta , indicating that two-stage cultivation is an efficient strategy for biodiesel production from microalgae. It was found that glycerol significantly enhanced cell biomass of D. tertiolecta , and the presence of glycerol alleviated the inhibitory effect of triethylamine on algal growth. Glycerol, the major byproduct from biodiesel production, was used for the biomass accumulation of D. tertiolecta at the first stage of cultivation. Triethylamine, as a lipid inducer, was used for lipid accumulation at the second stage of cultivation. Two-stage cultivation with glycerol and triethylamine enhanced lipid productivity and alleviated the inhibitory effect of triethylamine on the algal growth of D. tertiolecta , which is an efficient strategy for lipid production from D. tertiolecta ., (Copyright © 2019 American Society for Microbiology.)

Microalgae have been considered as alternative sustainable resources for high-value bioproducts such as lipids (especially triacylglycerides [TAGs]), polyunsaturated fatty acids (PUFAs), and carotenoids, due to their relatively high photosynthetic efficiency, no arable land requirement, and ease of scale-up. It is of great significance to exploit microalgae for the production of high-value bioproducts. How to improve the content or productivity of specific bioproducts has become one of the most urgent challenges. In this review, we will describe high-value bioproducts from microalgae and their biosynthetic pathways (mainly for lipids, PUFAs, and carotenoids). Recent progress and strategies for the enhanced production of bioproducts from microalgae are also described in detail, and these strategies take advantages of optimized cultivation conditions with abiotic stress, chemical stress (addition of metabolic precursors, phytohormones, chemical inhibitors, and chemicals inducing oxidative stress response), and molecular approaches such as metabolic engineering, transcriptional engineering, and gene disruption strategies (mainly RNAi, antisense RNA, miRNA-based knockdown, and CRISPR/Cas9).

Background: There has been little systematic examination of variation in pediatric burn care clinical practices and its effect on outcomes. As a first step, current clinical care processes need to be operationally defined. The highly specialized burn care units of the Shriners Hospitals for Children system present an opportunity to describe the processes of care. The aim of this study was to develop a set of process-based measures for pediatric burn care and examine adherence to them by providers in a cohort of pediatric burn patients., Methods: We conducted a systematic literature review to compile a set of process-based indicators. These measures were refined by an expert panel of burn care providers, yielding 36 process-based indicators in four clinical areas: initial evaluation and resuscitation, acute excisional surgery and critical care, psychosocial and pain control, and reconstruction and aftercare. We assessed variability in adherence to the indicators in a cohort of 1,076 children with burns at four regional pediatric burn programs in the Shriners Hospital system. The percentages of the cohort at each of the four sites were as follows: Boston, 20.8%; Cincinnati, 21.1%; Galveston, 36.0%; and Sacramento, 22.1%. The cohort included children who received care between 2006 and 2010., Results: Adherence to the process indicators varied both across sites and by clinical area. Adherence was lowest for the clinical areas of acute excisional surgery and critical care, with a range of 35% to 48% across sites, followed by initial evaluation and resuscitation (range, 34%-60%). In contrast, the clinical areas of psychosocial and pain control and reconstruction and aftercare had relatively high adherence across sites, with ranges of 62% to 93% and 71% to 87%, respectively. Of the 36 process indicators, 89% differed significantly in adherence between clinical sites (p < 0.05). Acute excisional surgery and critical care exhibited the most variability., Conclusion: The development of this set of process-based measures represents an important step in the assessment of clinical practice in pediatric burn care. Substantial variation was observed in practices of pediatric burn care. However, further research is needed to link these process-based measures to clinical outcomes., Level of Evidence: Therapeutic/care management, level IV.

Carotenoids are essential for photosynthesis and photoprotection in photosynthetic organisms and beneficial for human health. Apocarotenoids derived from carotenoid degradation can serve critical functions including hormones, volatiles, and signals. They have been used commercially as food colorants, animal feed supplements, and nutraceuticals for cosmetic and pharmaceutical purposes. This review focuses on the molecular evolution of carotenogenic enzymes and carotenoid cleavage oxygenases (CCOs) from bacteria, fungi, cyanobacteria, algae, and plants. The diversity of carotenoids and apocarotenoids as well as their complicated biosynthetic pathway in different species can shed light on the history of early molecular evolution. Some carotenogenic genes (such as phytoene synthases) have high protein sequence similarity from bacteria to land plants, but some (such as phytoene desaturases, lycopene cyclases, carotenoid hydroxylases, and CCOs) have low similarity. The broad diversity of apocarotenoid volatile compounds can be attributed to large numbers of carotenoid precursors and the various cleavage sites catalyzed by CCOs enzymes. A variety of carotenogenic enzymes and CCOs indicate the functional diversification of carotenoids and apocrotenoids in different species. New carotenoids, new apocarotenoids, new carotenogenic enzymes, new CCOs, and new pathways still need to be explored.

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups., Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria., Results: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM.", Conclusion: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria., (© 2017, American College of Rheumatology.)