The tea plant CsLHT1 and CsLHT6 transporters take up amino acids, as a nitrogen source, from the soil of organic tea plantations

Organic tea is more popular than conventional tea that originates from fertilized plants.Amino acids inorganic soils constitute a substantial pool nitrogen(N)available for plants.However,the amino-acid contents in soils of tea plantations and how tea plants take up these amino acids remain largely unknown.In this study,we show that the amino-acid content in the soil of an organic tea plantation is significantly higher than that of a conventional tea plantation.Glutamate,alanine,valine,and leucine were the most abundant amino acids in the soil of this tea plantation.When 15 N-glutamate was fed to tea plants,it was efficiently absorbed and significantly increased the contents of other amino acids in the roots.We cloned seven CsLHT genes encoding amino-acid transporters and found that the expression of CsLHT1,CsLHT2,and CsLHT6 in the roots significantly increased upon glutamate feeding.Moreover,the expression of CsLHT1 or CsLHT6 in a yeast amino-acid uptake-defective mutant,22Δ10α,enabled growth on media with amino acids constituting the sole N source.Amino-acid uptake assays indicated that CsLHT1 and CsLHT6 are H^(+)-dependent high-and low-affinity amino-acid transporters,respectively.We further demonstrated that CsLHT1 and CsLHT6 are highly expressed in the roots and are localized to the plasma membrane.Moreover,overexpression of CsLHT1 and CsLHT6 in Arabidopsis significantly improved the uptake of exogenously supplied 15 N-glutamate and 15 N-glutamine.Taken together,our findings are consistent with the involvement of CsLHT1 and CsLHT6 in amino-acid uptake from the soil,which is particularly important for tea plants grown inorganic tea plantations.

Reconstruction and Dynamics of the Human Intestinal Microbiome Observed In Situ

The human gut microbiome has primarily been studied through the use of fecal samples,a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities.However,this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract(in situ),and the infrequent availability of fecal samples prevents analysis at finer temporal scales(e.g.,hours).In our study,we utilized colonic transendoscopic enteral tubing,a technology originally developed for fecal microbiota transplantation,to sample the ileocecal microbiome twice daily;metagenomic and metatranscriptomic analyses were then conducted on these samples.A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers.The ileocecal and fecal microbiomes,as profiled in the five volunteers,were found to be similar in metagenomic profiling,yet their active genes(metatranscriptome)were found to be highly distinct.Both microbiomes were perturbed after laxative exposure;over time,they exhibited reduced dissimilarity to their pre-treatment state,thereby demonstrating resilience as an innate property of the gut microbiome,although they did not fully recover within our observation time window.Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways,particularly those related to short-chain fatty acid production,such as Propionibacterium acnes and coenzyme A biosynthesis Ⅱ.Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations.Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome,indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health.This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms,as well as the potential consequences of these to the host.

Instability of Nucleic Acids in Airborne Microorganisms under Far Infrared Radiation

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, and COVID-19, plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms containing RNA viruses was stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission by air and cure RNA virus infection were proposed. Then, this study suggests that FIR radiation has the potential to be a cheap, convenient, and efficient method in clinic to treat RNA virus.

A robust,integrated platform for comprehensive analyses of acylcoenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development

Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method.Levels of acyl-carnitines,which function to convey fatty acyls into mitochondria matrix forβ-oxidation,indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs.Herein,we report a robust,integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines.Using this method,we monitored changes in intermediary lipid profiles across Drosophila development under control(ND)and high-fat diet(HFD).We observed specific accumulations of medium-chain(C8-C12)and long-chain(≥C16)acyl-carnitines distinct to L3 larval and pupal stages,respectively.These observations suggested development-specific,chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development,which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra-and intra-mitochondrial acyl-CoA pools.We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs(accumulated as C12:0-carnitines in L3 stage)over C16:0-CoAs.Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs(C16-C18),leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6 A activity.HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa,thereby adversely affecting overall development.Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems.

Molecular insights into the transgenerational inheritance of stress memory

There is accumulating evidence to show that environmental stressors can regulate a variety of phenotypes in descendants through germline-mediated epigenetic inheritance. Studies of model organisms exposed to environmental cues(e.g., diet, heat stress, toxins) indicate that altered DNA methylations, histone modifications, or non-coding RNAs in the germ cells are responsible for the transgenerational effects. In addition,it has also become evident that maternal provision could provide a mechanism for the transgenerational inheritance of stress adaptations that result from ancestral environmental cues. However, how the signal of environmentally-induced stress response transmits from the soma to the germline, which may influence offspring fitness, remains largely elusive. Small RNAs could serve as signaling molecules that transmit between tissues and even across generations. Furthermore, a recent study revealed that neuronal mitochondrial perturbations induce a transgenerational induction of the mitochondrial unfolded protein response mediated by a Wnt-dependent increase in mitochondrial DNA levels. Here, we review recent work on the molecular mechanism by which parental experience can affect future generations and the importance of soma-to-germline signaling for transgenerational inheritance.

Haem Oxygenase 1 is a potential target for creating etiolated/albino tea plants (Camellia sinensis) with high theanine accumulation

Theanine content is highly correlated with sensory quality and health benefits of tea infusion.The tender shoots of etiolated and albino tea plants contain higher theanine than the normal green tea plants and are valuable materials for high quality green tea processing.However,why these etiolated or albino tea plants can highly accumulate theanine is largely unknown.In this study,we observed an Arabidopsis etiolated mutant hy1–100(mutation in Haem Oxygenase 1,HO1)that accumulated higher levels of glutamine(an analog of theanine).We therefore identified CsHO1 in tea plants and found CsHO1 is conserved in amino acid sequences and subcellular localization with its homologs in other plants.Importantly,CsHO1 expression in the new shoots was much lower in an etiolated tea plants‘Huangkui’and an albino tea plant‘Huangshan Baicha’than that in normal green tea plants.The expression levels of CsHO1 were negatively correlated with theanine contents in these green,etiolated and albino shoots.Moreover,CsHO1 expression levels in various organs and different time points were also negatively correlated with theanine accumulation.The hy1–100 was hypersensitive to high levels of theanine and accumulated more theanine under theanine feeding,and these phenotypes were rescued by the expression of CsHO1 in this mutant.Transient knockdown CsHO1 expression in the new shoots of tea plant using antisense oligonucleotides(asODN)increased theanine accumulation.Collectively,these results demonstrated CsHO1 negatively regulates theanine accumulation in tea plants,and that low expression CsHO1 likely contributes to the theanine accumulation in etiolated/albino tea plants.

Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the repair efficiency of SCI,we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold(LOCS).We confirmed that transplantation of this tissue regenerated neurons and synapses,improved the microenvironment of the injured area,enhanced remodeling of the extracellular matrix,and promoted functional recovery of the hind limbs in a rat SCI model with complete transection.RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI.Together,we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time.This tissue can effectively improve the therapeutic effect of SCI,thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

Erratum to“Nucleolar histone deacetylases HDT1,HDT2,and HDT3 regulate plant reproductive development”[Journal of Genetics and Genomics(2022)49,30–39]

This erratum clarifies information in the article“Nucleolar histone deacetylases HDT1,HDT2,and HDT3 regulate plant reproductive development”by Luo et al.(2021).In the section on“Phenotype of hdt mutants”,the T-DNA insertional knockdown mutant for HDT2(hdt2,salk_1247_A02)should be“Sail_1247_A02”in the main text and Fig.3A.

AB013.Tear lipidome and its implications

The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health.The composition of the tear film amphiphilic lipid sublayer,in particular,has largely remained a matter of contention.The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation.Using systematic and sensitive lipidomic approaches,we reported the most comprehensive human tear lipidome to date;and conferred novel insights to the compositional details of the existent tear film model,in particular the disputable amphiphilic lipid sublayer constituents,by demonstrating the presence of cholesteryl sulfate,O-acyl-ω-hydroxy fatty acids,and various sphingolipids and phospholipids in tears.Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome(DES)revealed structure-specific lipid alterations in DES,which could potentially serve as unifying indicators of disease symptoms and signs.The meibomian glands constitute the predominant source of lipid supply to the human tear fluid.Meibomian gland dysfunction(MGD)is a leading cause of evaporative dry eye and ocular discomfort,characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface.We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks.Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.

Inaugural Editorial:Seed Biology

Seed is the most important reproductive organ in plant.Since its first emergence approximately 370 million years ago,seed plant had overwhelming advantage to non-seed plants in reproduction,spreading and colonization in terrestrial land.Beside its essential function in the sexual reproduction of plants,seed is the most economically important agricultural product,offering necessity food for human and wildlife,nutritious feed for livestock.Seeds and grains also provide massive amount of raw materials for manufactured goods,such as coffee,starch,and oil.Seeds also play a pivotal role in development of fruits which supplement significant portion of food and nutrition for human and wildlife.

GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

Protein phosphorylation regulates a variety of important cellular and physiological processes in plants.In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes.This is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry analysis.To this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)mode.The mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and cost-effectiveness.The method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate motifs.GreenPhos is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

Aagab is required for zebrafish larval development by regulating neural activity

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen presentation.Despite prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains elusive.In this study,we investigate the biological function of aagab during zebrafish development.We establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval mortality.Given the high expression level of aagab in the brain,we probe into its physiological role in the nervous system.aagab mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab mutants.Overexpressing aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and survival.Furthermore,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle recycling.In conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy.Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)complexes.The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management.In this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid cycle.Leveraging this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4.Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

Erratum to “Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation”

Main Text In the Research Article“Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation”[1],there was an error in Fig.2B.The authors mistakenly repeated the chord diagram designated for P7 with that from P1.The figure amendment did not affect the in-text discussion of the figure,which was focused on changes between P0 and P21,and did not alter the conclusion.Figure 2B has now been corrected in the PDF and HTML(full text).

Results of the Second Life Metabolism Travel Awards 2024

This year is the second year of the Life Metabolism Travel Prize Awards for PhD students and postdocs.The three 700 US$awards are generously sponsored by Sable Systems-Promethion(China)who manufacture metabolic chambers.Before I announce the winners and their interesting projects,I will just reiterate how the judging of the awards works.We first remove anything from the submission that would identify the sex,affiliation,or ethnicity of the applicant.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility

Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.

Regulation of glucose and lipid metabolism in health and disease

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression

Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.

One-year clinical study of NeuroR egen scaffold implantation following scar resection in complete chronic spinal cord injury patients

The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, Neuro Regen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5–4.5 cm were surgically resected in five complete chronic spinal cord injury(SCI) patients. The NeuroR egen scaffold along with autologous bone marrow mononuclear cells(BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or Neuro Regen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials(SSEP) from the lower limbs was also detected. The results indicate that scar resection and Neuro Regen scaffold transplantation could be a promising clinical approach to treating SCI.