Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury.

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

Dynamic Nanocrystal Superlattices with Thermally Triggerable Lubricating Ligands.

The size-dependent and collective physical properties of nanocrystals (NCs) and their self-assembled superlattices (SLs) enable the study of mesoscale phenomena and the design of metamaterials for a broad range of applications. However, the limited mobility of NC building blocks in dried NCSLs often hampers the potential for employing postdeposition methods to produce high-quality NCSLs. In this study, we present tailored promesogenic ligands that exhibit a lubricating property akin to thermotropic liquid crystals. The lubricating ability of ligands is thermally triggerable, allowing the dry solid NC aggregates deposited on the substrates with poor ordering to be transformed into NCSLs with high crystallinity and preferred orientations. The interplay between the dynamic behavior of NCSLs and the molecular structure of the ligands is elucidated through a comprehensive analysis of their lubricating efficacy using both experimental and simulation approaches. Coarse-grained molecular dynamic modeling suggests that a shielding layer from mesogens prevents the interdigitation of ligand tails, facilitating the sliding between outer shells and consequently enhancing the mobility of NC building blocks. The dynamic organization of NCSLs can also be triggered with high spatial resolution by laser illumination. The principles, kinetics, and utility of lubricating ligands could be generalized to unlock stimuli-responsive metamaterials from NCSLs and contribute to the fabrication of NCSLs.

Rewiring the pneumococcal capsule pathway for investigating glycosyltransferase specificity and genetic glycoengineering.

Virtually all living cells are covered with glycans. Their structures are primarily controlled by the specificities of glycosyltransferases (GTs). GTs typically adopt one of the three folds, namely, GT-A, GT-B, and GT-C. However, what defines their specificities remain poorly understood. Here, we developed a genetic glycoengineering platform by reprogramming the capsular polysaccharide pathways in Streptococcus pneumoniae to interrogate GT specificity and manipulate glycan structures. Our findings suggest that the central cleft of GT-B enzymes is important for determining acceptor specificity. The constraint of the glycoengineering platform was partially alleviated when the specificity of the precursor transporter was reduced, indicating that the transporter contributes to the overall fidelity of glycan synthesis. We also modified the pneumococcal capsule to produce several medically important mammalian glycans, as well as demonstrated the importance of regiochemistry in a glycosidic linkage on binding lung epithelial cells. Our work provided mechanistic insights into GT specificity and an approach for investigating glycan functions.

Unraveling genomic regions and candidate genes for multiple disease resistance in upland cotton using meta-QTL analysis.

Verticillium wilt (VW), Fusarium wilt (FW) and Root-knot nematode (RKN) are the main diseases affecting cotton production. However, many reported quantitative trait loci (QTLs) for cotton resistance have not been used for agricultural practices because of inconsistencies in the cotton genetic background. The integration of existing cotton genetic resources can facilitate the discovery of important genomic regions and candidate genes involved in disease resistance. Here, an improved and comprehensive meta-QTL analysis was conducted on 487 disease resistant QTLs from 31 studies in the last two decades. A consensus linkage map with genetic overall length of 3006.59 cM containing 8650 markers was constructed. A total of 28 Meta-QTLs (MQTLs) were discovered, among which nine MQTLs were identified as related to resistance to multiple diseases. Candidate genes were predicted based on public transcriptome data and enriched in pathways related to disease resistance. This study used a method based on the integration of Meta-QTL, known genes and transcriptomics to reveal major genomic regions and putative candidate genes for resistance to multiple diseases, providing a new basis for marker-assisted selection of high disease resistance in cotton breeding.

GhSINA1, a SEVEN in ABSENTIA ubiquitin ligase, negatively regulates fiber development in Upland cotton.

Protein ubiquitination is essential for plant growth and responses to the environment. The SEVEN IN ABSENTIA (SINA) ubiquitin ligases have been extensively studied in plants, but information on their roles in fiber development is limited. Here, we identified GhSINA1 in Upland cotton (Gossypium hirsutum), which has a conserved RING finger domain and SINA domain. Quantitative real-time PCR (qRT-PCR) analysis showed that GhSINA1 was preferentially expressed during fiber initiation and elongation, especially during initiation in the fuzzless-lintless cotton mutant. Subcellular localization experiments indicated that GhSINA1 localized to the nucleus. In vitro ubiquitination analysis revealed that GhSINA1 has E3 ubiquitin ligase activity. Ectopic overexpression of GhSINA1 in Arabidopsis thaliana reduced the number and length of root hairs and trichomes. Yeast two-hybrid (Y2H), firefly luciferase complementation imaging (LCI), and bimolecular fluorescence complementation (BiFC) assays demonstrated that the GhSINA1 proteins could interact with each other to form homodimers and heterodimers. Overall, these results suggest that GhSINA1 may act as a negative regulator in cotton fiber development through homodimerization and heterodimerization.

Physiological and Biochemical Properties of Cotton Seedlings in Response to Cu2+ Stress.

Copper(II) (Cu2+) is essential for plant growth and development. However, high concentrations are extremely toxic to plants. We investigated the tolerance mechanism of cotton under Cu2+ stress in a hybrid cotton variety (Zhongmian 63) and two parent lines with different Cu2+ concentrations (0, 0.2, 50, and 100 µM). The stem height, root length, and leaf area of cotton seedlings had decreased growth rates in response to increasing Cu2+ concentrations. Increasing Cu2+ concentration promoted Cu2+ accumulation in all three cotton genotypes' roots, stems, and leaves. However, compared with the parent lines, the roots of Zhongmian 63 were richer in Cu2+ and had the least amount of Cu2+ transported to the shoots. Moreover, excess Cu2+ also induced changes in cellular redox homeostasis, causing accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Conversely, antioxidant enzyme activity increased, while photosynthetic pigment content decreased. Our findings indicated that the hybrid cotton variety fared well under Cu2+ stress. This creates a theoretical foundation for the further analysis of the molecular mechanism of cotton resistance to copper and suggests the potential of the large-scale planting of Zhongmian 63 in copper-contaminated soils.

Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

Correction: Development of a Therapeutic Video Game With the MDA Framework to Decrease Anxiety in Preschool-Aged Children With Acute Lymphoblastic Leukemia: Mixed Methods Approach.

[This corrects the article DOI: 10.2196/37079.].

Taurine promotes Oreochromis niloticus survival against Edwardsiella tarda infection.

Edwardsiella tarda represents one of the most important pathogens that infects a variety of hosts including aquatic animals and humans. The outbreak of E. tarda infection is frequently reported in aquaculture that causes huge economic loss. Due to the widespread of antibiotic resistance, available antibiotics to treat bacterial infection are limited. Therefore, enhancing aquatic animals to survive upon E. tarda infection become an urgent issue. In this study, we profiled the metabolomic change of tilapia in-between the dying and survival fish upon E. tarda infection. The dying and survival fish mounts differential metabolic response, from which we identify a key metabolite, taurine, whose abundance is increased in both the survival group and the dying group but is more significant in the survival group. Exogenous taurine increases tilapia survival rate by 37.5% upon E. tarda infection. Further quantitative PCR analysis demonstrate taurine increases the expression of immune genes in liver, spleen and head kidney. Therefore, our study shows a new strategy to enhance fish immune response against bacterial infection.

Development of a Therapeutic Video Game With the MDA Framework to Decrease Anxiety in Preschool-Aged Children With Acute Lymphoblastic Leukemia: Mixed Methods Approach.

BACKGROUND: Preschool-aged children with acute lymphoblastic leukemia (ALL) receive long-term treatment according to the Taiwan Pediatric Oncology Group (TPOG)-ALL 2013 protocol. Severe anxiety and noncompliance ahead of frequent invasive therapies leads to an increase in health care costs. Previous studies have shown that therapeutic video games (TVGs) can decrease the anxiety experienced by children who are ill. To our knowledge, no existing TVG has been designed specifically for preschool-aged children with ALL in Taiwan. OBJECTIVE: The purpose of this study was to develop a TVG using the popular Mechanics, Dynamics, and Aesthetics (MDA) framework for game design and to investigate the effect of this TVG on the reduction of therapy-related anxiety among preschool-aged children with ALL. METHODS: This study used a mixed methods approach over three phases: (1) develop a TVG using the MDA framework, (2) test the reliability of the TVG among three certified children's art therapists, and (3) evaluate the reduction of therapy-related anxiety among participants after using the TVG for 6 weeks, using a two-group, stratified randomized controlled trial at a medical center in northern Taiwan. Eligible preschool-aged children with ALL were randomly assigned 1:1 into an experimental group or a control group. The two groups of subjects received the same usual care, and only the experimental group had access to and used the TVG. The children's anxiety responses were reported by their family caregivers using the face rating scale (FRS). Descriptive analyses, the Fisher exact test, the Pearson chi-square test, and the Mann-Whitney U test were used to statistically analyze the variables. RESULTS: Six mechanics rules supported the dynamics of the TVG using four main features-character, nursery, tasks, and market-in order to complete all of the therapy-related anxiety reduction scenarios and to achieve eight aesthetics goals. The results of reliability test showed that participants found the TVG to be useful and trustworthy for preschool-aged children with ALL (Cronbach α=.98). A total of 15 participants were enrolled and randomly allocated to the experimental group (n=7) or the control group (n=8). The average number of TVG log-ins was 37.9 (SD 15.30, range 14-62) in the experimental group. The demographic data showed homogeneity across the two groups regarding age (3 to 5 years), sex (male), risk classification (standard risk), and treatment status (continuation therapy). The mean FRS score was 6.16 (SD 3.31) for the experimental group as compared to 7.45 (SD 2.71) for the control group (P=.04), which represented a significant difference between the groups at the 6-week follow-up. CONCLUSIONS: This research provides evidence that using a TVG can decrease anxiety in preschool-aged children with ALL in Taiwan. The TVG could be used to support clinical professionals before they perform invasive therapies. However, it is recommended to increase the statistical power for inference. TRIAL REGISTRATION: ClinicalTrials.gov NCT04199637; https://www.clinicaltrials.gov/ct2/show/NCT04199637.

Ginsenoside Rb1 inhibits astrocyte activation and promotes transfer of astrocytic mitochondria to neurons against ischemic stroke.

Astrocytes activation in response to stroke results in altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective potential. This work aimed to investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and mitochondrial transfer. We prepared conditioned astrocytes-derived medium for co-culture with neurons and examined the role of Rb1 in mitochondrial transfer from astrocytes to neurons. The neuroprotective potential of Rb1 was further confirmed in vivo using a mouse model of brain ischemia. In response to oxygen-glucose deprivation and reperfusion (OGD/R), astrocytes were reactivated and produced reactive oxygen species (ROS), an action that was blocked by Rb1. Mechanistically, Rb1 inhibited NADH dehydrogenase in mitochondrial complex I to block reverse electron transport-derived ROS production from complex I, and thus inactivated astrocytes to protect the mitochondria. Mitochondrial signal, mitochondrial membrane potential and ATP production detected in conditioned astrocyte-derived medium indicated that Rb1 protected functional mitochondria and facilitated their transfer. When neurons were injured by OGD/R insult, co-culturing with conditioned medium increased mitochondrial membrane potential and oxygen consumption rate within the neurons, indicating the protection conferred on them by Rb1 via mitochondrial transfer from astrocytes. Using the ischemic mouse brain model, CD38 knockdown in the cerebral ventricles diminished the neuroprotective effects of Rb1, providing evidence in support of the role of astrocyte mitochondrial transfer. Transient inhibition of mitochondrial complex I by Rb1 reduced mitochondrial ROS production and consequently avoided astrocyte activation. Astrocyte mitochondrial transfer therefore seemed a means by which Rb1 could promote neuronal survival and function. Different from the neurocentric view, these findings suggest the astrocytes may be a promising target for pharmacological interventions in ischemic brain injury.

The complete mitochondrial genome of Hemiclepsis yangtzenensis (Clitellata: Glossiphoniidae).

We present the complete mitochondrial genome sequence of a recently described new leech species named Hemiclepsis yangtzenensis Yang & Bolotov 2021 collected in central China. The mitochondrial genome is 14,984 bp in length and consists of 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, all of which are encoded on a single strand. It exhibited a strong A + T bias of 72.87%. There is a large non-coding region (614 bp) located between the tRNA-Arg and tRNA-His genes, wherein we identified 40 short dispersed repeats, 13-22 bp long, 8 of which were direct, 20 inverted, and 12 palindromic. Phylogenetic analysis of 20 Hirudinea mitogenome sequences resolved monophyletic Glossiphoniidae, and H. yangtzenensis formed a sister lineage with Glossiphonia concolor.

Effect of Peer Victimization on the Long-Term Mental Health Status among Adults Users of Intellectual Disability Services: A Longitudinal Follow-Up Study.

Caregiving for mental health among people with intellectual disabilities (IDs) in the ID services was reported as insufficient. The purposes of this study were to investigate five types of peer victimization (PV) experiences among adults with ID using ID services, and to gain a deeper understanding of the influence of PV experience on adults with ID's long-term mental health status. A one-year longitudinal follow-up study was conducted from eight long-term care ID services (n = 176). Logistic regression analysis was applied to variables comprising personal characteristics, various types of PV experience and polyvictimization to predict period prevalence of psychiatric symptoms. The data indicated that nearly one-third of individuals with ID experienced at least one psychiatric symptom. The three most common psychiatric symptoms prevalent after one year were adjustment disorder, anxiety disorder, and somatoform disorder. Over the 1-year study period, approximately 40% of adults with ID reported experiencing PV. The most frequently reported types of PV were physical force (26%) and verbal victimization (22%). Polyvictimization was experienced by approximately a quarter of adults with ID. The findings suggest that PV is a common experience among adults in ID services. Thus, for a clearer understanding of mental health risks, caregivers should pay attention to adults with ID who experienced PV.

Role of alternative activation of macrophages in hookworm therapy for inflammatory diseases: a review / 中国血吸虫病防治杂志

As a type of highly plastic innate immune cells, macrophages may be differentiated into M1 and M2 macrophages upon different stimuli, and M2 macrophages are involved in immune regulation, tissue remodeling and regeneration, and wound healing. Previous epidemiological studies have shown a significant negative correlation between the prevalence of helminth infections and the incidence of inflammatory diseases, such as allergy and autoimmune diseases. As a common type of intestinal helminths, hookworm infection may trigger high levels of type II host immune responses, with alternative activation of macrophages, which are effective to inhibit the development and progression of inflammatory diseases. This review summarizes the advances in alternative activation of macrophages in hookworm therapy for inflammatory diseases.

Regulation of melanocortin-5 receptor pharmacology by two isoforms of MRAP2 in ricefield eel (Monopterus albus).

The melanocortin-5 receptor (MC5R) has been implicated in the regulation of exocrine gland secretion, immune regulation, and muscle fatty acid oxidation in mammals. Melanocortin-2 receptor accessory protein 2 (MRAP2) can modulate trafficking, ligand binding, and signaling of melanocortin receptors. To explore potential interaction between ricefield eel (Monopterus albus) MC5R and MRAP2s (maMC5R, maMRAP2X1, and maMRAP2X2), herein we studied the pharmacological characteristics of maMC5R and its modulation by maMRAP2s expressed in the human embryonic kidney cells. Three agonists, α-melanocyte-stimulating hormone (α-MSH), ACTH (1-24), and [Nle4, D-Phe7]-α-MSH, could bind to maMC5R and induce intracellular cAMP production dose-dependently. Compared with human MC5R (hMC5R), maMC5R displayed decreased maximal binding but higher binding affinity to α-MSH or ACTH (1-24). When stimulated with α-MSH or ACTH (1-24), maMC5R showed significantly lower EC50 and maximal response than hMC5R. Two maMRAP2s had no effect on cell surface expression of maMC5R, whereas they significantly increased maximal binding. Only maMRAP2X2 significantly decreased the binding affinity of ACTH (1-24). Both maMRAP2X1 and maMRAP2X2 significantly reduced maMC5R efficacy but did not affect ligand sensitivity. The availability of maMC5R pharmacological characteristics and modulation by maMRAP2s will assist the investigation of its roles in regulating diverse physiological processes in ricefield eel.

Molecular Design of Three-Dimensional Metal-Free A(NH4)X3 Perovskites for Photovoltaic Applications.

The intense research activities on the hybrid organic-inorganic perovskites (HOIPs) have led to the greatly improved light absorbers for solar cells with high power conversion efficiency (PCE). However, it is still challenging to find an alternative lead-free perovskite to replace the organohalide lead perovskites to achieve high PCE. This is because both previous experimental and theoretical investigations have shown that the Pb2+ cations play a dominating role in contributing the desirable frontier electronic bands of the HOIPs for light absorbing. Recent advances in the chemical synthesis of three-dimensional (3D) metal-free perovskites, by replacing Pb2+ with NH4 +, have markedly enriched the family of multifunctionalized perovskites (Ye et al., Science2018, 361, 151-155). These metal-free perovskites possess the chemical formula of A(NH4)X3, where A is divalent organic cations and X denotes halogen atoms. Without involving transition-metal cations, the metal-free A(NH4)X3 perovskites can entail notably different frontier electronic band features from those of the organohalide lead perovskites. Indeed, the valence and conduction bands of A(NH4)X3 perovskites are mainly attributed by the halogen atoms and the divalent A2+ organic cations, respectively. Importantly, a linear relationship between the bandgaps of A(NH4)X3 perovskites and the lowest unoccupied molecular orbital energies of the A2+ cations is identified, suggesting that bandgaps can be tailored via molecular design, especially through a chemical modification of the A2+ cations. Our comprehensive computational study and molecular design predict a metal-free perovskite, namely, 6-ammonio-1-methyl-5-nitropyrimidin-1-ium-(NH4)I3, with a desirable bandgap of ∼1.74 eV and good optical absorption property, both being important requirements for photovoltaic applications. Moreover, the application of strain can further fine-tune the bandgap of this metal-free perovskite. Our proposed design principle not only offers chemical insights into the structure-property relationship of the multifunctional metal-free perovskites but also can facilitate the discovery of highly efficient alternative, lead-free perovskites for potential photovoltaic or optoelectronic applications.

Serine Metabolism Tunes Immune Responses To Promote Oreochromis niloticus Survival upon Edwardsiella tarda Infection.

Overactive immune response is a critical factor triggering host death upon bacterial infection. However, the mechanism behind the regulation of excessive immune responses is still largely unknown, and the corresponding control and preventive measures are still to be explored. In this study, we find that Nile tilapia, Oreochromis niloticus, that died from Edwardsiella tarda infection had higher levels of immune responses than those that survived. Such immune responses are strongly associated with metabolism that was altered at 6 h postinfection. By gas chromatography-mass spectrometry-based metabolome profiling, we identify glycine, serine, and threonine metabolism as the top three of the most impacted pathways, which were not properly activated in the fish that died. Serine is one of the crucial biomarkers. Exogenous serine can promote O. niloticus survival both as a prophylactic and therapeutic upon E. tarda infection. Our further analysis revealed exogenous serine flux into the glycine, serine, and threonine metabolism and, more importantly, the glutathione metabolism via glycine. The increased glutathione synthesis could downregulate reactive oxygen species. Therefore, these data together suggest that metabolic modulation of immune responses is a potential preventive strategy to control overactive immune responses. IMPORTANCE Bacterial virulence factors are not the only factors responsible for host death. Overactive immune responses, such as cytokine storm, contribute to tissue injury that results in organ failure and ultimately the death of the host. Despite the recent development of anti-inflammation strategies, the way to tune immune responses to an appropriate level is still lacking. We propose that metabolic modulation is a promising approach in tuning immune responses. We find that the metabolomic shift at as early as 6 h postinfection can be predictive of the consequences of infection. Serine is a crucial biomarker whose administration can promote host survival upon bacterial infection either in a prophylactic or therapeutic way. Further analysis demonstrated that exogenous serine promotes the synthesis of glutathione, which downregulates reactive oxygen species to dampen immune responses. Our study exemplifies that the metabolite(s) is a potential therapeutic reagent for overactive immune response during bacterial infection.

Novel Structural Variation and Evolutionary Characteristics of Chloroplast tRNA in Gossypium Plants.

Cotton is one of the most important fiber and oil crops in the world. Chloroplast genomes harbor their own genetic materials and are considered to be highly conserved. Transfer RNAs (tRNAs) act as "bridges" in protein synthesis by carrying amino acids. Currently, the variation and evolutionary characteristics of tRNAs in the cotton chloroplast genome are poorly understood. Here, we analyzed the structural variation and evolution of chloroplast tRNA (cp tRNA) based on eight diploid and two allotetraploid cotton species. We also investigated the nucleotide evolution of chloroplast genomes in cotton species. We found that cp tRNAs in cotton encoded 36 or 37 tRNAs, and 28 or 29 anti-codon types with lengths ranging from 60 to 93 nucleotides. Cotton chloroplast tRNA sequences possessed specific conservation and, in particular, the Ψ-loop contained the conserved U-U-C-X3-U. The cp tRNAs of Gossypium L. contained introns, and cp tRNAIle contained the anti-codon (C-A-U), which was generally the anti-codon of tRNAMet. The transition and transversion analyses showed that cp tRNAs in cotton species were iso-acceptor specific and had undergone unequal rates of evolution. The intergenic region was more variable than coding regions, and non-synonymous mutations have been fixed in cotton cp genomes. On the other hand, phylogeny analyses indicated that cp tRNAs of cotton were derived from several inferred ancestors with greater gene duplications. This study provides new insights into the structural variation and evolution of chloroplast tRNAs in cotton plants. Our findings could contribute to understanding the detailed characteristics and evolutionary variation of the tRNA family.

Succinate Promotes Phagocytosis of Monocytes/Macrophages in Teleost Fish.

Development of immunity-based strategy to manage bacterial infection is urgently needed in aquaculture due to the widespread of antibiotic-resistant bacteria. Phagocytosis serves as the first line defense in innate immunity that engulfs bacteria and restricts their proliferations and invasions. However, the mechanism underlying the regulation of phagocytosis is not fully elucidated and the way to boost phagocytosis is not yet explored. In this manuscript, we profiled the metabolomes of monocytes/macrophages isolated from Nile tilapia, prior and after phagocytosis on Vibrio alginolyticus. Monocytes/macrophages showed a metabolic shift following phagocytosis. Interestingly, succinate was accumulated after phagocytosis and was identified as a crucial biomarker to distinguish before and after phagocytosis. Exogenous succinate increased the phagocytotic rate of monocytes/macrophages in a dose-dependent manner. This effect was dependent on the TCA cycle as the inhibitor of malonate that targets succinate dehydrogenase abrogated the effect. Meanwhile, exogenous succinate regulated the expression of genes associated with innate immune and phagocytosis. In addition, succinate-potentiated phagocytosis was applicable to both gram-negative and -positive cells, including V. alginolyticus, Edwardsiella tarda, Streptococcus agalactiae, and Streptococcus iniae. Our study shed light on the understanding of how modulation on host's metabolism regulates immune response, and this can be a potent therapeutic approach to control bacterial infections in aquaculture.

Enhanced PEMFC durability with graphitized carbon black cathode catalyst supports under accelerated stress testing.

The anti-corrosion properties of the carbon substrates of cathode catalysts play a vital role in the commercialization of fuel cell vehicles. Our report reveals the enhanced durability of graphitized carbon black catalyst substrates in polymer electrolyte membrane fuel cells (PEMFCs), tested under simulated start-stop cycling and high potential holding conditions. Graphitized carbon treated at various temperatures is used as the support for Pt catalysts. The catalyst utilizing graphitized carbon treated at 1800 °C demonstrates superior antioxidation properties and the inhibition of Pt particle coarsening. The decay ratio of the potential at 1000 mA cm-2 has been reduced from 34.9% (commercial Pt/C) to 0.5% during high potential holding accelerated stress testing. Correspondingly, the growth of Pt particles is reduced from 0.95 nm (commercial Pt/C) to 0.08 nm; that is, the coalescence of Pt particles is effectively alleviated upon using graphitized carbon black.