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1.
ACS Appl Mater Interfaces ; 16(21): 27794-27803, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38748448

ABSTRACT

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

2.
Nat Commun ; 15(1): 3795, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714679

ABSTRACT

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.


Subject(s)
Cytokines , Lyme Disease , Quantitative Trait Loci , Lyme Disease/immunology , Lyme Disease/genetics , Lyme Disease/microbiology , Humans , Cytokines/genetics , Cytokines/metabolism , Male , Female , Interleukin-10/genetics , Adult , Genome-Wide Association Study , Middle Aged , Interleukin 1 Receptor Antagonist Protein/genetics , Borrelia burgdorferi/immunology , Borrelia burgdorferi/genetics , Anti-Bacterial Agents , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Aged
3.
Molecules ; 29(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38611810

ABSTRACT

A single combi oven, known for its versatility, is an excellent choice for a variety of chicken soup preparations. However, the impact of universal steam ovens on the flavor quality of chicken soup remains unclear. This study aimed to explore the impact of different cooking methods on the aroma and taste of chicken soup. Three cooking methods with various stewing times were compared: ceramic pot (CP), electric pressure cooker (EPC), and combi oven (CO). Analyses were conducted using electron-nose, electron-tongue, gas chromatography-ion mobility spectrometry (GC-IMS), automatic amino acid analysis, and chemometric methods. A total of 14 amino acids, including significant umami contributors, were identified. The taste components of CP and CO chicken soups were relatively similar. In total, 39 volatile aroma compounds, predominantly aldehydes, ketones, and alcohols, were identified. Aldehydes were the most abundant compounds, and 23 key aroma compounds were identified. Pearson's correlation analyses revealed distinct correlations between various amino acids (e.g., glutamic acid and serine) and specific volatile compounds. The aroma compounds from the CP and CO samples showed similarities. The results of this study provide a reference for the application of one-touch cooking of chicken soup in versatile steam ovens.


Subject(s)
Antifibrinolytic Agents , Odorants , Animals , Chickens , Steam , Taste , Gas Chromatography-Mass Spectrometry , Amino Acids , Aldehydes , Cooking
4.
BMC Infect Dis ; 24(1): 337, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38515037

ABSTRACT

BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).


Subject(s)
Borrelia burgdorferi Group , Borrelia burgdorferi , Borrelia , Lyme Disease , Humans , Genome-Wide Association Study , Prospective Studies , Leukocytes, Mononuclear , Disease Susceptibility , Lyme Disease/genetics , Lyme Disease/diagnosis , Borrelia burgdorferi/genetics , Cytokines/genetics , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/therapeutic use , Borrelia burgdorferi Group/genetics , Secretoglobins/genetics
5.
Mech Ageing Dev ; 218: 111916, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38364983

ABSTRACT

In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with ex-vivo cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses.


Subject(s)
Aging , East African People , European People , Aged , Humans , Cytokines , Immunity, Innate , Metabolome
6.
Joint Bone Spine ; 91(3): 105698, 2024 May.
Article in English | MEDLINE | ID: mdl-38309518

ABSTRACT

OBJECTIVE: Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation. METHODS: Peripheral blood mononuclear cells (PBMCs) from gout patients, hyperuricemic and normouricemic individuals were cultured for 24h with varying concentrations of soluble urate, followed by 24h restimulation with lipopolysaccharides (LPS)±monosodium urate (MSU) crystals. Transcriptomic profiling was performed using RNA-Sequencing. DNA methylation was assessed using Illumina Infinium® MethylationEPIC BeadChip system (EPIC array). Phosphorylation of signal transducer and activator of transcription 3 (STAT3) was determined by flow cytometry. Cytokine responses were also assessed in PBMCs from patients with JAK2 V617F tyrosine kinase mutation. RESULTS: PBMCs pre-treated with urate produced more interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) and less interleukin-1 receptor anatagonist (IL-1Ra) after LPS simulation. In vitro, urate treatment enhanced SOCS3 expression in control monocytes but no DNA methylation changes were observed at the SOCS3 gene. A dose-dependent reduction in phosphorylated STAT3 concomitant with a decrease in IL-1Ra was observed with increasing concentrations of urate. PBMCs with constitutively activated STAT3 (JAK2 V617F mutation) could not be primed by urate. CONCLUSION: In vitro, urate exposure increased SOCS3 expression, while urate priming, and subsequent stimulation resulted in decreased STAT3 phosphorylation and IL-1Ra production. There was no evidence that DNA methylation constitutes a regulatory mechanism of SOCS3. Elevated SOCS3 and reduced pSTAT3 could play a role in urate-induced hyperinflammation since urate priming had no effect in PBMCs from patients with constitutively activated STAT3.


Subject(s)
Cytokines , Gout , STAT3 Transcription Factor , Suppressor of Cytokine Signaling 3 Protein , Uric Acid , Humans , Suppressor of Cytokine Signaling 3 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/genetics , Uric Acid/pharmacology , STAT3 Transcription Factor/metabolism , Cytokines/metabolism , Gout/genetics , Gout/metabolism , Cells, Cultured , Male , Myeloid Cells/metabolism , Myeloid Cells/drug effects , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/drug effects , Hyperuricemia/metabolism , Female , Middle Aged , DNA Methylation , Janus Kinase 2/metabolism
7.
Immunity ; 57(1): 171-187.e14, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38198850

ABSTRACT

Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity. We established personal immune profiles and chromatin accessibility maps over a 90-day time course of BCG vaccination in 323 individuals. Our analysis uncovered genetic and epigenetic predictors of baseline immunity and immune response. BCG vaccination enhanced the innate immune response specifically in individuals with a dormant immune state at baseline, rather than providing a general boost of innate immunity. This study advances our understanding of BCG's heterologous immune-stimulatory effects and trained immunity in humans. Furthermore, it highlights the value of epigenetic cell states for connecting immune function with genotype and the environment.


Subject(s)
BCG Vaccine , Trained Immunity , Humans , Multiomics , Vaccination , Epigenesis, Genetic
8.
J Leukoc Biol ; 115(1): 149-163, 2024 01 05.
Article in English | MEDLINE | ID: mdl-37672677

ABSTRACT

Bacillus Calmette-Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both adaptive and innate immunity, γδ T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human γδ T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette-Guérin vaccine. We investigated in vivo induction of innate memory in γδ T cells by Bacillus Calmette-Guérin vaccination in healthy human volunteers by combining single-cell RNA sequencing technology with immune functional assays. The total number of γδ T cells and membrane markers of activation was not influenced by Bacillus Calmette-Guérin vaccination. In contrast, Bacillus Calmette-Guérin changed γδ T cells' transcriptional programs and increased their responsiveness to heterologous bacterial and fungal stimuli, including lipopolysaccharide and Candida albicans, as simultaneously characterized by higher tumor necrosis factor and interferon γ production, weeks after vaccination. Human γδ T cells in adults display the potential to develop a trained immunity phenotype after Bacillus Calmette-Guérin vaccination.


Subject(s)
BCG Vaccine , Mycobacterium bovis , Adult , Humans , Trained Immunity , Interferon-gamma , Immunity, Innate , Vaccination
9.
Waste Manag Res ; 42(1): 74-80, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37102342

ABSTRACT

Since the majority of valuable components in spent lithium-ion batteries, such as lithium, exists in the electrode materials, common studies focused on the treatment of the cathode materials, which ignored the harm of residual electrolyte. The cavitation and thermal effects produced by ultrasonic can not only be used for the separation of electrode materials, but also have a wide range of applications in the field of sewage pollutant degradation. This work used ultrasonic to treat simulated electrolyte (propylene carbonate (PC)) solution of spent lithium-ion batteries, explored the effect of ultrasonic power, the addition amount of H2O2 solution (30 wt%) and reaction temperature on the degradation of electrolyte, and analysed the ultrasonic degradation reaction from the perspective of reaction kinetics. And the synchronous experiment of cathode material separation and electrolyte degradation was conducted under the optimal conditions. The results showed that the highest degradation efficiency of PC in the electrolyte was 83.08% under the condition of ultrasonic power of 900 W, the addition of H2O2 solution (30 wt%) of 10.2 mL, reaction temperature of 120°C and reaction time of 120 minutes, and the separation efficiency was 100%. This work reduced the environmental and health risks in the cathode material separation process and was conducive to the green development of spent lithium-ion battery recycling technology.


Subject(s)
Lithium , Ultrasonics , Hydrogen Peroxide , Recycling/methods , Electric Power Supplies , Electrodes
10.
EBioMedicine ; 99: 104935, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38134621

ABSTRACT

BACKGROUND: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. METHODS: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments. FINDINGS: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. INTERPRETATION: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. FUNDING: Found in acknowledgements.


Subject(s)
Cortodoxone , Progesterone , Humans , Androstenedione , Steroids , Phenotype
11.
Nat Commun ; 14(1): 6172, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37794016

ABSTRACT

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.


Subject(s)
Dermatitis, Atopic , Genome-Wide Association Study , Humans , Dermatitis, Atopic/genetics , Genetic Predisposition to Disease/genetics , Hispanic or Latino/genetics , Black People , Polymorphism, Single Nucleotide
12.
Pharmacol Ther ; 250: 108508, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37567513

ABSTRACT

Epigenetics functions as a bridge between host genetic & environmental factors, aiding in human health and diseases. Many immune-related diseases, including infectious and allergic diseases, have been linked to epigenetic mechanisms, particularly DNA methylation. In this review, we summarized an updated overview of DNA methylation and its importance in personalized medicine, and demonstrated that DNA methylation has excellent potential for disease prevention, diagnosis, and treatment in a personalized manner. The future implications and limitations of the DNA methylation study have also been well-discussed.


Subject(s)
DNA Methylation , Hypersensitivity , Humans , Precision Medicine , Epigenesis, Genetic , Hypersensitivity/genetics , Epigenomics
13.
Biomedicines ; 11(6)2023 May 25.
Article in English | MEDLINE | ID: mdl-37371624

ABSTRACT

Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation.

14.
Food Sci Technol Int ; : 10820132231173158, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37166957

ABSTRACT

To improve the edible qualities of meatballs, various percentages of pork fat in meatballs were replaced by brown flaxseed flour (BFF) to decrease the fat contents and further optimize the fatty acid compositions. Five different meatball formulations that used 0%, 5%, 10%, 15%, and 20% of flaxseed flour additions were used in which the corresponding amounts pork fat were replaced. The proximate compositions, water activity, pH levels, colors, textures, cooking losses, fatty acid compositions, sensory properties, flavors, and oxidation stabilities of these meatballs were analyzed. Increasing the BFF addition amounts improved the protein and dietary fiber contents, pH levels, fatty acid profiles and oxidation stabilities, but decreased the fat contents, moisture levels, cooking losses, n6/n3 ratios, hardness, and lightness. The volatile flavors of meatballs with different BFF replacement levels were significantly different. According to the sensory evaluation, the use of 5% BFF increased the odor of meatballs without significantly affecting the other sensory scores. This work demonstrated that BFF may be a healthier alternative as pork fat replacer for preparing meatballs.

15.
Cell Rep ; 42(5): 112487, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37155329

ABSTRACT

Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8+ T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.


Subject(s)
Mycobacterium bovis , Humans , Mycobacterium bovis/metabolism , BCG Vaccine , Trained Immunity , CD8-Positive T-Lymphocytes , Interferon-gamma/metabolism , Immunity, Innate
16.
Adv Mater ; 35(29): e2300813, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37080594

ABSTRACT

Thermal protection under extreme conditions requires materials with excellent thermal insulation properties and exceptional mechanical properties to withstand a variety of complex external stresses. Mesoporous silica aerogels are the most widely used insulation materials due to their ultralow thermal conductivity. However, they still suffer from mechanical fragility and structural instability in practical applications. Herein, a nacre-mimetic nanocomposite aerogel, synthesized via in situ growth of inorganic minerals in a lamellar cellulose nanofibrous network, is reported. The multiscale structural adaptation of the inorganic-organic components endows nanocomposite aerogels with rapid configuration recovery during ambient pressure drying. The resulting aerogels show ultralow thermal conductivities (17.4 mW m-1  K-1 at 1.0 atm). These aerogels also integrate challenging mechanical properties, including high compressive stiffness to resist deformation under the pressure of an adult, superelasticity to prevent static and dynamic stress cracking even under the crushing of a vehicle (1.6 t), and high bending flexibility to adapt to any surface. Moreover, they exhibit excellent structural stability under fatigue stress/strain cycles over a wide temperature range (-196 to 200 °C). The combination of high thermal insulation performance and excellent mechanical properties offers a potential material system for robust thermal superinsulation under extreme conditions, especially for aerospace applications.

17.
Nanomicro Lett ; 15(1): 64, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36899127

ABSTRACT

Solar-driven interfacial evaporation is an emerging technology for water desalination. Generally, double-layered structure with separate surface wettability properties is usually employed for evaporator construction. However, creating materials with tunable properties is a great challenge because the wettability of existing materials is usually monotonous. Herein, we report vinyltrimethoxysilane as a single molecular unit to hybrid with bacterial cellulose (BC) fibrous network, which can be built into robust aerogel with entirely distinct wettability through controlling assembly pathways. Siloxane groups or carbon atoms are exposed on the surface of BC nanofibers, resulting in either superhydrophilic or superhydrophobic aerogels. With this special property, single component-modified aerogels could be integrated into a double-layered evaporator for water desalination. Under 1 sun, our evaporator achieves high water evaporation rates of 1.91 and 4.20 kg m-2 h-1 under laboratory and outdoor solar conditions, respectively. Moreover, this aerogel evaporator shows unprecedented lightweight, structural robustness, long-term stability under extreme conditions, and excellent salt-resistance, highlighting the advantages in synthesis of aerogel materials from the single molecular unit.

18.
EMBO Rep ; 24(4): e55747, 2023 04 05.
Article in English | MEDLINE | ID: mdl-36916532

ABSTRACT

Metabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. Here, we provide an overview on recent technological developments of metabolomic applications in immunological research. To begin, two widely used metabolomics approaches are compared: targeted and untargeted metabolomics. Then, we provide a comprehensive overview of the analysis workflow and the computational tools available, including sample preparation, raw spectra data preprocessing, data processing, statistical analysis, and interpretation. Third, we describe how to integrate metabolomics with other omics approaches in immunological studies using available tools. Finally, we discuss new developments in metabolomics and its prospects for immunology research. This review provides guidance to researchers using metabolomics and multiomics in immunity research, thus facilitating the application of systems immunology to disease research.


Subject(s)
Metabolomics , Multiomics , Research Design
19.
J Viral Hepat ; 30(7): 597-606, 2023 07.
Article in English | MEDLINE | ID: mdl-36924318

ABSTRACT

Bulevirtide (BLV) is an entry inhibitor blocking entry of HBsAg into hepatocytes by interfering with the bile acid transporter Na+-taurocholate co-transporting polypeptide. We here investigated if bile acid levels before or during BLV treatment would correlate with HDV RNA declines. We studied 20 patients with compensated HDV infection receiving a daily dose of 2 mg bulevirtide subcutaneously qd for at least 24 weeks. ALT levels improved in all patients including 13/20 patients showing normal ALT values at treatment Week 24. An HDV RNA drop of at least 50% was evident in 20/20 patients at Week 24 including 10 patients showing a ≥ 2 log HDV RNA decline. Elevated bile acid levels were detected already before treatment in 10 patients and further increased during BLV administration with different kinetics. Baseline bile acids were associated with higher transient elastography values (p = .0029) and evidence of portal hypertension (p = .0004). Bile acid levels before treatment were associated with HDV RNA declines throughout therapy, but not at Week 24 (rho = -0.577; p = .0078; rho = -0.635, p = .0026; rho = -0.577, p = .0077; rho = -0.519, p = .0191; rho = -0.564, p = .0119 and rho = -0.393, p = .087 at treatment Weeks 2, 8, 12, 16, 20 and 24, respectively). However, bile acid increases during treatment were not associated with HDV RNA or ALT declines at any of the time points. BLV-induced increases in bile salts do not correlate with HDV RNA declines suggesting that the inhibitory effects of BLV on NTCP differ between blocking bile acid transport and hindering HBsAg entry. If baseline bile salt levels could be useful to predict virological response remains to be confirmed.


Subject(s)
Hepatitis D , Hepatitis Delta Virus , Humans , RNA , Hepatitis B Surface Antigens , Bile Acids and Salts , Hepatitis D/drug therapy , Hepatitis B virus , Antiviral Agents
20.
Nat Commun ; 14(1): 119, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36650136

ABSTRACT

The energy transition will require a rapid deployment of renewable energy (RE) and electric vehicles (EVs) where other transit modes are unavailable. EV batteries could complement RE generation by providing short-term grid services. However, estimating the market opportunity requires an understanding of many socio-technical parameters and constraints. We quantify the global EV battery capacity available for grid storage using an integrated model incorporating future EV battery deployment, battery degradation, and market participation. We include both in-use and end-of-vehicle-life use phases and find a technical capacity of 32-62 terawatt-hours by 2050. Low participation rates of 12%-43% are needed to provide short-term grid storage demand globally. Participation rates fall below 10% if half of EV batteries at end-of-vehicle-life are used as stationary storage. Short-term grid storage demand could be met as early as 2030 across most regions. Our estimates are generally conservative and offer a lower bound of future opportunities.

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