Miracle-dz/UniFAR-FTUs huggingface dataset:
Phloroglucinol Promotes Fucoxanthin Synthesis by Activating the cis-Zeatin and Brassinolide Pathways in Thalassiosira pseudonana

Here, we demonstrate that phloroglucinol, a growth promoter in higher plants, also increases growth and fucoxanthin synthesis in the microalga Thalassiosira pseudonana and therefore may have substantial practical application for industrial fucoxanthin production. Phloroglucinol treatment also induced the synthesis of cis-zeatin and brassinolide in T. pseudonana, and the cis-zeatin and brassinolide signaling pathways were implicated in the phloroglucinol-driven increases in T. pseudonana growth and fucoxanthin synthesis. ABSTRACT Phloroglucinol improves shoot formation and somatic embryogenesis in several horticultural and grain crops, but its function in microalgae remains unclear. Here, we found that sufficiently high concentrations of phloroglucinol significantly increased fucoxanthin synthesis, growth, and photosynthetic efficiency in the microalga Thalassiosira pseudonana. These results suggested that the role of phloroglucinol is conserved across higher plants and microalgae. Further analysis showed that, after phloroglucinol treatment, the contents of cis-zeatin and brassinolide in T. pseudonana increased significantly, while the contents of trans-zeatin, N6-isopentenyladenine (iP), auxin, and gibberellin were unaffected. Indeed, functional studies showed that the effects of cis-zeatin and brassinolide in T. pseudonana were similar to those of phloroglucinol. Knockout of key enzyme genes in the cis-zeatin synthesis pathway of T. pseudonana or treatment of T. pseudonana with a brassinolide synthesis inhibitor (brassinazole) significantly reduced growth and fucoxanthin content in T. pseudonana, and phloroglucinol treatment partially alleviated these inhibitory effects. However, phloroglucinol treatment was ineffective when the cis-zeatin and brassinolide pathways were simultaneously inhibited. These results suggested that the cis-zeatin and brassinolide signaling pathways are independent regulators of fucoxanthin synthesis in T. pseudonana and that phloroglucinol affects both pathways. Thus, this study not only characterizes the mechanism by which phloroglucinol promotes fucoxanthin synthesis but also demonstrates the roles of cis-zeatin and brassinolide in T. pseudonana. IMPORTANCE Here, we demonstrate that phloroglucinol, a growth promoter in higher plants, also increases growth and fucoxanthin synthesis in the microalga Thalassiosira pseudonana and therefore may have substantial practical application for industrial fucoxanthin production. Phloroglucinol treatment also induced the synthesis of cis-zeatin and brassinolide in T. pseudonana, and the cis-zeatin and brassinolide signaling pathways were implicated in the phloroglucinol-driven increases in T. pseudonana growth and fucoxanthin synthesis. Thus, our work clarified the molecular mechanism of phloroglucinol promoting the growth and fucoxanthin synthesis of Thalassiosira pseudonana and suggested that cis-zeatin and brassinolide, in addition to phloroglucinol, have potential utility as inducers of increased microalgal fucoxanthin production.
Staying in place and moving in space: Contrasting larval thermal sensitivity explains distributional changes of sympatric sea urchin species to habitat warming

For marine ectotherms, larval success, planktonic larval duration and dispersal trajectories are strongly influenced by temperature, and therefore, ocean warming and heatwaves have profound impacts on these sensitive stages. Warming, through increased poleward flow in regions with western boundary currents, such as the East Australia Current (EAC), provides opportunities for range extension as propagules track preferred conditions. Two sea urchin species, Centrostephanus rodgersii and Heliocidaris tuberculata, sympatric in the EAC warming hotspot, exhibit contrasting responses to warming. Over half a century, C. rodgersii has undergone marked poleward range extension, but the range of H. tuberculata has not changed. We constructed thermal performance curves (TPC) to determine if contrasting developmental thermal tolerance can explain this difference. The temperatures tested encompassed present‐day distribution and forecast ocean warming/heatwave conditions. The broad and narrow thermal optimum (Topt) ranges for C. rodgersii and H. tuberculata larvae (7.2 and 4.7°C range, respectively) matched their realized (adult distribution) thermal niches. The cool and warm temperatures for 50% development to the feeding larva approximated temperatures at adult poleward range limits. Larval cool tolerances with respect to mean local temperature differed, 6.0 and 3.8°C respectively. Larval warm tolerances were similar for both species as are the adult warm range edges. The larvae of both species would be sensitive to heatwaves. Centrostephanus rodgersii has stayed in place and shifted in space, likely due to its broad cold–warm larval thermal tolerance and large thermal safety margins. Phenotypic plasticity of the planktonic stage of C. rodgersii facilitated its range extension. In contrast, larval cold intolerance of H. tuberculata explains its restricted range and will delay poleward extension as the region warms. In a warming ocean, we show that intrinsic thermal biology traits of the pelagic stage provide an integrative tool to explain species‐specific variation in range shift patterns.
Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8+ T cells

eEF-2K has important roles in stress responses and cellular metabolism. We report here a previously unappreciated but critical role of eEF-2K in regulating the fate and cytocidal activity of CD8+ T cells. CD8+ T cells from eEF-2K KO mice were more proliferative but had lower survival than their wild-type counterparts after their activation, followed by occurrence of premature senescence and exhaustion. eEF-2K KO CD8+ T cells were more metabolically active and showed hyperactivation of the Akt-mTOR-S6K pathway. Loss of eEF-2K substantially impaired the activity of CD8+ T cells. Furthermore, the antitumor efficacy and tumor infiltration of the CAR-CD8+ T cells lacking eEF-2K were notably reduced as compared to the control CAR-CD8+ T cells. Thus, eEF-2K is critically required for sustaining the viability and function of cytotoxic CD8+ T cells, and therapeutic augmentation of this kinase may be exploited as a novel approach to reinforcing CAR-T therapy against cancer.
The effects of hydroxyurea on proinflammatory cytokine and tissue histopathology in an experimental sepsis model.

OBJECTIVE The diagnosis and treatment of sepsis are costly to healthcare services, and it is an important disease with high mortality rates. In the pathogenesis of sepsis, for which we still cannot provide a complete cure, there is increased cytokine release and organ damage. Hydroxyurea has been shown to reduce leukocyte counts, decrease inflammatory cytokines, and limit organ inflammation in ischemia-reperfusion models. This study aimed to evaluate leukocyte counts, interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) cytokine values and organ inflammatory processes in hydroxyurea-treated rats with an experimental sepsis model. MATERIALS AND METHODS After ethical approval, rats were randomly divided into three groups, control (n= 7), sepsis (n= 7), and hydroxyurea (n= 7). Sepsis was created using the cecal ligation and puncture (CLP) method in rats other than in the control group. Rats in the hydroxyurea group received hydroxyurea (200 mg/kg) intragastrically, and the control and sepsis groups received sterile distilled water. IL-1β, IL-6, and TNF-α levels were measured at 0, 8, and 24 hours after CLP in all rats. Blood samples were collected at the time of sacrification 24 hours after CLP and analyzed for the complete blood count. Tissue specimens were taken for histopathologic examination. RESULTS Cytokine levels (IL-1β, IL-6, TNF-α), white blood cell counts, and tissue damage were increased after the sepsis model in rats. It was found that the cytokine levels at the 8th hour, white blood cell count, and brain tissue damage in the hydroxyurea group were decreased significantly compared with the sepsis group. CONCLUSIONS Early hydroxyurea treatment in rats with sepsis decreases proinflammatory cytokine (IL-1β, IL-6, and TNF-α) levels and thus reduces brain damage.
Caffeine ingestion attenuates diurnal variation of lower-body ballistic performance in resistance-trained women

ABSTRACT The present study investigates the effect of an acute intake of caffeine on the diurnal variation of neuromuscular performance in resistance-trained women. A total of 15 resistance-trained women participated in the current triple-blind, placebo-controlled, crossover experimental study. We assessed neuromuscular performance (i.e. ballistic (countermovement jump [CMJ] height and bench press throw [BPT] peak velocity), maximal strength (squat and bench press [BP] one-repetition maximum [1RM]), and strength-endurance [average velocity of the set during squat and number of repetitions-to-failure in BP]) four times at within 7 days. The participants ingested an acute dose of caffeine (3 mg/kg) or a placebo at 9–11 am and/or 17–19 pm. CMJ height (P = .016) and BP peak velocity (P = .012) were higher in the afternoon than in the morning. Compared to placebo, caffeine intake increased CMJ height by 3.1% in the morning and 1.6% in the afternoon (P = .035), but it had no effect on BPT peak velocity (P = .381). Maximal strength and strength-endurance performances were not affected by the time-of-day or caffeine intake (all P > .3). No significant interaction (time-of-day x substance) was observed in any of the above-mentioned outcomes (all P > .1). In conclusion, an acute dose of caffeine in the morning was effective to restore CMJ performance to levels found in the afternoon, while this effect was not observed neither in BPTpeak velocity nor in lower- and upper-body maximal strength and strength-endurance performance. Moreover, lower- and upper-body ballistic performance were greater in the afternoon than in the morning in resistance-trained women, while the acute intake of caffeine was only effective to increase CMJ height. Highlights Ballistic performance is probably higher in the afternoon than in the morning in resistance-trained women. An acute intake of caffeine is effective to increase countermovement jump performance. The ingestion of an acute dose of caffeine in the morning restored countermovement jump performance to levels found in the afternoon.
Spermidine Regulates Mitochondrial Function by Enhancing eIF5A Hypusination and Contributes to Reactive Oxygen Species Production and Ganoderic Acid Biosynthesis in Ganoderma lucidum

Spermidine is necessary for organism survival and is involved in the regulation of various biological processes. However, the specific mechanisms underlying the various physiological functions of spermidine are poorly understood, especially in microorganisms. ABSTRACT Spermidine, a kind of polycation and one important member of the polyamine family, is essential for survival in many kinds of organisms and participates in the regulation of cell growth and metabolism. To explore the mechanism by which spermidine regulates ganoderic acid (GA) biosynthesis in Ganoderma lucidum, the effects of spermidine on GA and reactive oxygen species (ROS) contents were examined. Our data suggested that spermidine promoted the production of mitochondrial ROS and positively regulated GA biosynthesis. Further research revealed that spermidine promoted the translation of mitochondrial complexes I and II and subsequently influenced their activity. With a reduction in eukaryotic translation initiation factor 5A (eIF5A) hypusination by over 50% in spermidine synthase gene (spds) knockdown strains, the activities of mitochondrial complexes I and II were reduced by nearly 60% and 80%, respectively, and the protein contents were reduced by over 50%, suggesting that the effect of spermidine on mitochondrial complexes I and II was mediated through its influence on eIF5A hypusination. Furthermore, after knocking down eIF5A, the deoxyhypusine synthase gene (dhs), and the deoxyhypusine hydroxylase gene (dohh), the mitochondrial ROS level was reduced by nearly 50%, and the GA content was reduced by over 40%, suggesting that eIF5A hypusination contributed to mitochondrial ROS production and GA biosynthesis. In summary, spermidine maintains mitochondrial ROS homeostasis by regulating the translation and subsequent activity of complexes I and II via eIF5A hypusination and promotes GA biosynthesis via mitochondrial ROS signaling. The present findings provide new insight into the spermidine-mediated biosynthesis of secondary metabolites. IMPORTANCE Spermidine is necessary for organism survival and is involved in the regulation of various biological processes. However, the specific mechanisms underlying the various physiological functions of spermidine are poorly understood, especially in microorganisms. In this study, we found that spermidine hypusinates eIF5A to promote the production of mitochondrial ROS and subsequently regulate secondary metabolism in microorganisms. Our study provides a better understanding of the mechanism by which spermidine regulates mitochondrial function and provides new insight into the spermidine-mediated biosynthesis of secondary metabolites.
Negatively Regulated Aerobactin and Desferrioxamine E by Fur in Pantoea ananatis Are Required for Full Siderophore Production and Antibacterial Activity, but Not for Virulence

Pantoea ananatis is a bacterium that causes diseases in several economically important crops, as well as in insects and humans. This bacterium has been studied extensively as a potentially dangerous pathogen due to its saprophytic ability. ABSTRACT Pantoea ananatis is an emerging plant pathogen that causes disease in economically important crops such as rice, corn, onion, melon, and pineapple, and it also infects humans and insects. In this study, we identified biosynthetic gene clusters of aerobactin and desferrioxamine E (DFO-E) siderophores by using the complete genome of P. ananatis PA13 isolated from rice sheath rot. P. ananatis PA13 exhibited the strongest antibacterial activity against Erwinia amylovora and Yersinia enterocolitica (Enterobacterales). Mutants of aerobactin or DFO-E maintained antibacterial activity against E. amylovora and Y. enterocolitica, as well as in a siderophore activity assay. However, double aerobactin and DFO-E gene deletion mutants completely lost siderophore and antibacterial activity. These results reveal that both siderophore biosynthetic gene clusters are essential for siderophore production and antibacterial activity in P. ananatis PA13. A ferric uptake regulator protein (Fur) mutant exhibited a significant increase in siderophore production, and a Fur-overexpressing strain completely lost antibacterial activity. Expression of the iucA, dfoJ, and foxA genes was significantly increased in the Δfur mutant background, and expression of these genes returned to wild-type levels after fur compensation. These results indicate that Fur negatively regulates aerobactin and DFO-E siderophores. However, siderophore production was not required for P. ananatis virulence in plants, but it appears to be involved in the microbial ecology surrounding the plant environment. This study is the first to report the regulation and functional characteristics of siderophore biosynthetic genes in P. ananatis. IMPORTANCE Pantoea ananatis is a bacterium that causes diseases in several economically important crops, as well as in insects and humans. This bacterium has been studied extensively as a potentially dangerous pathogen due to its saprophytic ability. Recently, the types, biosynthetic gene clusters, and origin of the siderophores in the Pantoea genus were determined by using genome comparative analyses. However, few genetic studies have investigated the characteristics and functions of siderophores in P. ananatis. The results of this study revealed that the production of aerobactin and desferrioxamine E in the rice pathogen P. ananatis PA13 is negatively regulated by Fur and that these siderophores are essential for antibacterial activity against Erwinia amylovora and Yersinia enterocolitica (Enterobacterales). However, siderophore production was not required for P. ananatis virulence in plants, but it appears to be involved in the microbial ecology surrounding the plant environment.
The validation of contemporary body composition methods in various races and ethnicities

Abstract Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94–2·37 %; FFM: TE = 0·72–1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52–2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21–2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3–4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.
Occupational and environmental exposures, the association with chronic sinusitis

Objectives: To find the association between environmental and occupational exposures and chronic rhinosinusitis (CRS) development. Methods: The Preferred Reporting Items Of Systematic Reviews Guidelines were used when a systematic literature review was conducted to find all published cases of CRS by searching PubMed database and Google Scholar. Published articles between 1989 and 2021 that reported chronic and occupational rhinosinusitis were included. However, articles that reported allergic rhinitis or upper airway diseases and non-English articles were excluded from this study. Results: A total of 97 articles were extracted initially, and 15 articles were reviewed after excluding 82 articles that did not match our inclusion criteria. Most studies linked CRS development to smoke exposure (n=9734), followed by living in rural areas as farms (n=5504). Exposure to pesticides (n=4248) contributed to a higher prevalence of CRS. Blue-collar occupations, such as fire fighters, farmers, and fishermen were significantly related to CRS development in a total of 5260 patients. Chronic rhinosinusitis mainly affected more men (n=8912) than women (n=8076). Conclusion: We found that smoking was the most aggravating environmental factor. Chronic rhinosinusitis symptoms’ severity increased with direct contact with allergens. Thus, the greatest proportion of patients with CRS was those with blue-collar occupations, such as firefighters, farmers, and fishermen.
Dominance of Cyclobutadienyl Over Cyclopentadienyl in the Crystal Field Splitting in Dysprosium Single‐Molecule Magnets

Abstract Replacing a monoanionic cyclopentadienyl (Cp) ligand in dysprosium single‐molecule magnets (SMMs) with a dianionic cyclobutadienyl (Cb) ligand in the sandwich complexes [(η4‐Cb′′′′)Dy(η5‐C5Me4 t Bu)(BH4)]− (1), [(η4‐Cb′′′′)Dy(η8‐Pn†)K(THF)] (2) and [(η4‐Cb′′′′)Dy(η8‐Pn†)]− (3) leads to larger energy barriers to magnetization reversal (Cb′′′′=C4(SiMe3)4, Pn†=1,4‐di(tri‐isopropylsilyl)pentalenyl). Short distances to the Cb′′′′ ligands and longer distances to the Cp ligands in 1–3 are consistent with the crystal field splitting being dominated by the former. Theoretical analysis shows that the magnetic axes in the ground Kramers doublets of 1–3 are oriented towards the Cb′′′′ ligands. The theoretical axiality parameter and the relative axiality parameter Z and Z rel are introduced to facilitate comparisons of the SMM performance of 1–3 with a benchmark SMM. Increases in Z and Z rel when Cb′′′ replaces Cp signposts a route to SMMs with properties that could surpass leading systems.
The associations of cannabis and methamphetamine use with cognitive performance over the first 2 years of treatment in schizophrenia spectrum disorders

Cognitive deficits are a core feature of schizophrenia, and comorbid substance use may be a contributory factor. Methamphetamine use has been associated with cognitive impairment in schizophrenia, while associations with cannabis use are less clear‐cut. This study aimed to investigate the associations of cannabis and methamphetamine use with cognitive performance in first‐episode schizophrenia spectrum disorders over the first 2 years of treatment.
Characterization of GefA, a GGEEF Domain-Containing Protein That Modulates Vibrio parahaemolyticus Motility, Biofilm Formation, and Virulence

The c-di-GMP metabolic enzymes constitute one of the largest clusters of potential orthologues in Vibrio parahaemolyticus. However, the specific roles that these individual c-di-GMP metabolic enzymes play are largely unknown. ABSTRACT Vibrio parahaemolyticus is a significant foodborne pathogen that causes economic and public health problems worldwide and has a high capacity to adapt to diverse environments and hosts. The second messenger cyclic diguanylate monophosphate (c-di-GMP) allows bacteria to shift from a planktonic form to a communal multicellular lifestyle and plays an important role in bacterial survival and transmission. Here, we characterized single-domain c-di-GMP synthetases in V. parahaemolyticus and identified a novel GGEEF domain-containing protein designated GefA that modulates bacterial swarming motility, biofilm formation, and virulence. GefA inhibits swarming motility by regulating the expression of lateral flagella, while it enhances biofilm formation by controlling exopolysaccharide biosynthesis. Under high-c-di-GMP conditions caused by scrABC knockout, we found that GefA is bifunctional, as it has no effect on swarming motility, but retains the ability to regulate biofilm formation. Subsequent studies suggested that GefA regulates the expression of type III secretion system 1 (T3SS1), which is an important virulence factor in V. parahaemolyticus. Here, we also revealed that the flagella participate in the infection of V. parahaemolyticus. We found that both the T3SS1 and flagella contribute to the GefA-mediated virulence of V. parahaemolyticus in the zebrafish model. Our results expand the knowledge of the V. parahaemolyticus c-di-GMP synthetases and their roles in social behaviors and pathogenicity. IMPORTANCE The c-di-GMP metabolic enzymes constitute one of the largest clusters of potential orthologues in Vibrio parahaemolyticus. However, the specific roles that these individual c-di-GMP metabolic enzymes play are largely unknown. Here, we identified a GGEEF domain-containing protein designated GefA that regulates bacterial behaviors and virulence. We also demonstrated that flagella participate in the infection of this bacterium, through which GefA regulates bacterial virulence. To our knowledge, the roles that c-di-GMP and flagella play in V. parahaemolyticus virulence have never been revealed. Our findings contribute to a better understanding of the function of c-di-GMP and its synthetases in V. parahaemolyticus.