Metabolic Activity Research Articles

Loss of the histone chaperone UNC-85/ASF1 inhibits the epigenome-mediated longevity and modulates the activity of one-carbon metabolism.

Histone H3/H4 chaperone anti-silencing function 1 (ASF1) is a conserved factor mediating nucleosomal assembly and disassembly, playing crucial roles in processes such as replication, transcription, and DNA repair. Nevertheless, its involvement in aging has remained unclear. Here, we utilized the model organism Caenorhabditis elegans to demonstrate that the loss of UNC-85, the homolog of ASF1, leads to a shortened lifespan in a multicellular organism. Furthermore, we show that UNC-85 is required for epigenome-mediated longevity, as knockdown of the histone H3 lysine K4 methyltransferase ash-2 does not extend the lifespan of unc-85 mutants. In this context, we found that the longevity-promoting ash-2 RNA interference enhances UNC-85 activity by increasing its nuclear localization. Finally, our data indicate that the loss of UNC-85 increases the activity of one-carbon metabolism, and that downregulation of the one-carbon metabolism component dao-3/MTHFD2 partially rescues the short lifespan of unc-85 mutants. Together, these findings reveal UNC-85/ASF1 as a modulator of the central metabolic pathway and a factor regulating a pro-longevity response, thus shedding light on a mechanism of how nucleosomal maintenance associates with aging.

Effect of immersion time on bacterial community structure and sulfur metabolism in biofilm on concrete surface in sewer environment

This study focuses on an overlooked but critical issue: the composition and functional expression of microbial communities on the concrete surface in different areas of sewer pipes. Three immersion conditions were applied to simulate the duration of concrete in different areas ofsewers exposed to sewage, including short-term (L1), long-term (L2) and permanent immersion (L3). The properties of concrete under different immersion conditions and the bacterial diversity and functional capabilities in biofilms on the concrete surface were analyzed. Results showed that the L1 group was dominated by Halothiobacillus, whereas Desulfomicrobium was prominent in the L3 group. Significant differences in the predominant functional microbial communities and metabolic functional genes further confirmed the strong impact of immersion time on the pathways of microbial sulfur metabolism and concrete performance in sewer environment. Compared with the L2 and L3 groups, the decreased sewage immersion time resulted in an increase in the abundance and metabolic activity of sulfur-oxidizing bacteria in the L1 group. Hence, greater mass loss and gypsum production of concrete was found in the L1 group. The structural and functional differentiation of bacterial communities on the concrete surface observed in this study contributes to a better understanding of the uneven corrosion in real sewer pipes.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when involving mutagens and carcinogens whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drugs and pollutant of emerging concern and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found on levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower while DFC only induced low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the increasing concern that co-exposure to environmental toxicants and their non-additive interactions can be a confounding factor that should not be neglected in environmental and human health risk assessment.

Using rice straw-augmented ecological floating beds to enhance nitrogen removal in carbon-limited wastewater

Agricultural biomass used as solid carbon substrates in ecological floating beds (EFBs) has been proven to be applicable in nitrogen removal for carbon-limited wastewater treatment. However, the subtle interactions among plants, rhizosphere microorganisms, and supplementary carbon sources have not been thoroughly studied. This study combined rice straw mats with different aquatic macrophytes in EFBs to investigate denitrification efficiency in carbon-limited eutrophic waters. Results showed that rice straw significantly enhanced the nitrogen removal efficiency of EFBs, while enriching nitrogen-fixing and denitrifying bacteria (such as Rhizobium, Rubrivivax, and Rhodobacter, etc.). Additionally, during the denitrification process in EFBs, rice straw can release humic acid-like fraction as electron donors to support the metabolic activities of microorganisms, while aquatic macrophytes provide a more diverse range of dissolved organic matters, facilitating a sustainable denitrification process. These findings help to understand the synergistic effect of denitrification processes within wetland ecosystems using agricultural biomass.

Nanowire-assisted electroporation via inducing cell destruction for inhibiting formation of VBNC bacteria: Comparison with chlorination

The induction of viable but nonculturable (VBNC) bacteria with cellular integrity and low metabolic activity by chemical disinfection causes a significant underestimation of potential microbiological risks in drinking water. Herein, a physical Co3O4 nanowire-assisted electroporation (NW-EP) was developed to induce cell damage via the locally enhanced electric field over nanowire tips, potentially achieving effective inhibition of VBNC cells as compared with chemical chlorination (Cl2). NW-EP enabled over 5-log removal of culturable cell for various G+/G- bacteria under voltage of 1.0 V and hydraulic retention time of 180 s, and with ∼3–6 times lower energy consumption than Cl2. NW-EP also achieved much higher removals (∼84.6 % and 89.5 %) of viable Bacillus cereus (G+) and Acinetobacter schindleri (G-) via generating unrecoverable pores on cell wall and reversible/irreversible pores on cell membrane than Cl2 (∼28.6 % and 41.1 %) with insignificant cell damage. The residual VBNC bacteria with cell wall damage and membrane pore resealing exhibited gradual inactivation by osmotic stress, leading to ∼99.8 % cell inactivation after 24 h storage (∼59.4 % for Cl2). Characterizations of cell membrane integrity and cell morphology revealed that osmotic stress promoted cell membrane damage for the gradual inactivation of VBNC cells during storage. The excellent adaptability of NW-EP for controlling VBNC cells in DI, tap and lake waters suggested its promising application potentials for drinking water, such as design of an external device on household taps.

Cellular Impact and Biodegradability of S‐ and N‐Doped Graphene Quantum Dots on Human Monocytes and Macrophages

AbstractGraphene quantum dots (GQDs), small graphene domains with lateral dimensions lower than 10 nm, are increasingly used in electronics, composites, and biomedicine. Chemical doping of GQDs allows tuning their optical properties. Immune cells are among the first cells exposed to nanomaterials entering a living body, rapidly triggering a downstream immune response. However, the assessment of the impact of chemically‐doped GQDs on the immune system remains rather limited if not absent. In this context, the effects and the biodegradability of sulfur‐doped and nitrogen‐doped GQDs (S‐GQDs and N‐GQDs) on human monocytes and macrophages are evaluated. The metabolic activity, membrane integrity, apoptosis, and intracellular reactive oxygen species (ROS) generation are studied. In parallel, the degradation of GQDs using human myeloperoxidase and a peroxynitrite‐mediated system is investigated in test tube. Their degradation in macrophages is also pursued. High‐resolution transmission electron microscopy (HRTEM), fluorescence spectroscopy, Raman, and flow cytometry are used to confirm the degradation. Overall, both GQDs exert little activation on monocytes and macrophages although they decrease the metabolic viability in a dose‐dependent manner. The loss of native GQD structure and crystal lattice provide evidence of their biodegradability. Both the safety and biodegradability of S‐GQDs and N‐GQDs ensure their potential in biomedical applications.

Targeting the mitochondrial protein YME1L to inhibit osteosarcoma cell growth in vitro and in vivo

Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.

Ribosomal dormancy at the nexus of ribosome homeostasis and protein synthesis.

Dormancy or hibernation is a non-proliferative state of cells with low metabolic activity and gene expression. Dormant cells sequester ribosomes in a translationally inactive state, called dormant/hibernating ribosomes. These dormant ribosomes are important for the preservation of ribosomes and translation shut-off. While recent studies attempted to elucidate their modes of formation, the regulation and roles of the diverse dormant ribosomal populations are still largely understudied. The mechanistic details of the formation of dormant ribosomes in stress and especially their disassembly during recovery remain elusive. In this review, we discuss the roles of dormant ribosomes and their potential regulatory mechanisms. Furthermore, we highlight the paradigms that need to be answered in the field of ribosomal dormancy.

Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis

Background: Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer.Methods: Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters.Results: Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered.Conclusion: This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.

Enhancing anaerobic digestion of actual papermaking wastewater with addition of Fenton sludge

The effect of Fenton sludge on anaerobic digestion of actual papermaking wastewater was investigated in this study. The results showed the iron in the Fenton sludge primarily exists in the form of needle-like iron oxide (FeOOH) and showed high electron transfer capability. Fenton sludge promoted electron transport in anaerobic digestion and electron transport system activity increased by 59 %. Fenton sludge enhanced the metabolic activity of anaerobic microorganisms, especially that of the hydrogenotrophic methanogens, the content of coenzyme F420 increased by 48.9 %. Besides, the microbial community structure in anaerobic digestion was affected by Fenton sludge, the quantity of microorganisms increased significantly. The dissimilatory iron-reducing bacteria (Desulfobacterota) and hydrogenotrophic methanogens (Methanobacterium and Methanolinea) were enriched, which promoted the methane production. As a result, the anaerobic digestion performance of papermaking wastewater was promoted significantly by adding Fenton sludge, the organic matter removal efficiency and methane production increased by 11.17 % and 15.12 %. This study provided an effective solution for the optimisation of anaerobic treatment of actual refractory organic wastewater.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

Dynamics of blood osteomarkers in the treatment of generalized periodontitis

AIM. Study of the dynamics of bone metabolism in the treatment of generalized periodontitis.MATERIALS AND METHODS. 60 patients with chronic generalized periodontitis of moderate to severe severity were examined and treated. A group of 15 healthy individuals without periodontal disease served as a control group. To assess the dynamics of bone formation, blood parameters were measured for bone metabolism: osteocalcin levels, alkaline phosphatase levels, and β-CrossLaps levels. Densitometry of the proximal femoral and lumbar spine regions was also performed.RESULTS. The study revealed increased bone metabolism compared with the control group, an increase in bone metabolism activity was found 3 months after treatment of patients with chronic generalized periodontitis, and after 12 months the values of the studied parameters did not differ from the control group.CONCLUSIONS. Thus, when treating generalized periodontitis, it is necessary to use a treatment regimen that takes into account the individual mineral metabolism of the patient’s bone tissue.

The association between leptin, adiponectin levels and the ovarian reserve in women of reproductive age

BackgroundReproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with high metabolic activity as it produces adipokines such as leptin and adiponectin. Our aim is to examine potential associations between women of reproductive age’s ovarian reserves and their levels of leptin and adiponectin.Method74 women between 19 and 40 years of age consented to take part. Based on the patterns of their ovarian reserves, the women were divided into three main groups: women with adequate ovarian reserves (AOR - Group A, n=30), women with polycystic ovary syndrome (PCOS - Group B, n=31) and women with depleted ovarian reserves (DOR - Group C, n=13). Among these groups, several biochemical and demographic parameters were statistically compared.ResultsCompared to the other two groups, women with DOR had statistically higher age and follicle stimulation hormone (FSH) levels. For estradiol (E2) and thyroid-stimulating hormone (TSH), no statistically significant difference was seen between the groups. In addition, women with PCOS had higher body mass index (BMI), luteinizing hormone (LH), total testosterone (TT), 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), anti-Mullerian hormone (AMH), and antral follicle count (AFC) than the other two groups. In line with expectations, women with DOR also had lower levels of AMH and AFC than the other two groups. Women with PCOS had higher leptin levels than the other two groups, but there was no statistically significant difference. Women with PCOS had lower levels of adiponectin than the other groups, however the difference was not statistically significant.ConclusionThe way we classified women in our study according to their ovarian reserves is completely consistent with what has been published internationally. The ovarian reserve in women of reproductive age is not strongly correlated with leptin and adiponectin levels. For safe conclusions, more research including a greater number of samples is required.

Novel Palladium Hydride Surface Enabling Simultaneous Bacterial Killing and Osteogenic Formation through Proton Capturing and Activation of Antioxidant System in Immune Microenvironments.

Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, we introduce a novel surface design-a palladium hydride (PdHx) film that enables these two distinct features to coexist. The PdHx lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdHx activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species (ROS). This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. Our findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials. This article is protected by copyright. All rights reserved.

Elevated CO2 concentration enhance carbon and nitrogen metabolism and biomass accumulation of Ormosiahosiei

Elevated CO2 concentrations may inhibit photosynthesis due to nitrogen deficiency, but legumes may be able to overcome this limitation and continue to grow. Our study confirms this conjecture well. First, we placed the two-year-old potted saplings of Ormosia hosiei (O. hosiei) (a leguminous tree species) in the open-top chamber (OTC) with three CO2 concentrations of 400 (CK), 600 (E1), and 800 μmol·mol−1 (E2) to simulate the elevated CO2 concentration environment. After 146 days, the light saturation point (LSP), light compensation point (LCP), apparent quantum efficiency (AQE), and dark respiration rate (Rd) of O. hosiei were increased under increasing CO2 concentration and obtain the maximum ribulose diphosphate (RuBP) carboxylation rate (Vc max) and RuBP regenerated photosynthetic electron transfer rate (Jmax) were also significantly increased under E2 treatment (P < 0.05). This results in a significant increase of the maximum assimilation rate (Amax) under elevated CO2 concentrations. Sucrose phosphate synthase (SPS) activity in sucrose metabolism increased in the leaves, more soluble sugars, starches, and sucrose was produced, but sucrose content only in leaves increased at E2, and more carbon flows to the roots. The activity of the NH4+ assimilating enzymes glutamine synthetase (GS), glutamate synthetase (GOGAT), and glutamate dehydrogenase (GDH) in the leaves of O. hosiei increases under elevated CO2 concentrations to promote nitrogen synthesis that reduces the content of ammonium nitrogen and increases the content of nitrate nitrogen. In addition, under E1 conditions, sucrose synthase (SS), direction of synthesis activity was highest and sucrose invertase (INV) activity was lowest, this means that the balance of C and N metabolism is maintained. While under E2 conditions SS activity decreased and INV activity increased, this increased C/N and nitrogen use efficiency. So, the elevated CO2 concentration promotes the accumulation of O. hosiei biomass, especially in the aboveground part, but did not have a significant effect on the accumulation of root biomass. This means that O. hosiei is able to cope under the elevated CO2 concentration without showing photosynthetic adaptation during the experimental period.

Microbial impact on basalt‐water‐hydrogen system: Insights into wettability, capillary pressure, and interfacial tension for subsurface hydrogen storage

AbstractHydrogen (H2) fuel is assessed to be a major component of sustainable energy systems in the net‐zero world. However, hydrogen storage is challenging and requires safe and environmentally friendly solutions like H2 geo‐sequestration. This study evaluates the effects of sulphate‐reducing bacteria (SRB) on H2 geological storage potential in the basalt rock. Fourier‐transform infrared spectroscopy (FTIR) findings show the presence of significant components, that is, O‐Si‐O and organic functional groups, that is, aromatics, amine salts, alkane, and cyclohexane in the basalt rock immersed in the nutrient solution without SRB. However, we found that C‐H stretching modes of organics with peaks at 1,465 cm−1 were observed. Consequently, amine salt (N‐H) (850–750 cm−1), solvent impurities (C‐H), and alkane spectrums are components of nutrient solutions and can be results of metabolic microbial activity that can influence on the surface of the basalt rock. Hence, these changes indicate the presence of microbial activity which might affect the surface chemistry of the rock leading to wettability alteration. We observed that the contact angle (θ) of brine‐H2 on the rock surface slightly changed from 500 to 4,000 psi pressure after the effect of bacteria at 50 °C. The wettability changed the surface of the rock from strong water‐wet to weak or intermediate water‐wet condition (i.e., θ &lt; 75°) at 4,000 psi and temperatures 25 and 50 °C after the bacteria effect. The affiliation of brine water reduces on the rock surface with increasing temperatures and pressures, even without microbial influence. Additionally, we investigated interfacial tension and capillary pressure on SRB bacteria treated basalt which is not yet reported in the published work. Interfacial tension (IFT) and Pc of H2 were reduced by 19% and 65%, respectively at 50 °C and 4,000 psi after the bacteria effect. Hence, the above findings could help to answer the key factors of the reservoir rock including wettability, capillary pressure, and interfacial tension to plan a field‐scale H2 geo‐sequestration strategy under the influence of biotic life. © 2024 Society of Chemical Industry and John Wiley &amp; Sons, Ltd.

WHEN CLINICAL FINDINGS TAKE YOU DOWN THE WRONG PATH: PERSISTENT FEVER IN A PATIENT WITH PREVIOUS CARDIAC SURGERY

Abstract Introduction In a patient who underwent previous cardiac surgery, persistent fever may be related to endocarditis. Symptoms and cardiovascular imaging, such as echocardiogram and PET/CT, may guide clinicians and surgeons to the correct diagnosis. Discussion A 43–years–old man came to our attention because of persistent fever (lasting several months) associated with cough and asthenia. When he was 5 years old, he underwent cardiac surgery for partial atrioventricular canal defect (atrial septal defect was about 4 cm) and mitral valve cleft. 14 years ago he undertook chemotherapy due to Hodgkin‘s lymphoma. Recently a cerebral artery aneurysm, radiologically defined as mycotic but proved to be fusiform, was diagnosed and treated with neurosurgery. During a recent hospitalization, blood culture positive for Streptococcus Mitis and brachial rash were reported and antibiotic therapy was started. Suspecting endocarditis, he was referred to our department. Echocardiogram revealed anterior mitral leaflet fissure, resulting in severe mitral regurgitation. Moreover a periannular cavity of doubtful interpretation (seemingly an abscess) was described. Subsequent 18FDG–PET/CT did not detect any abnormal cardiac metabolic activity. Due to severe valve regurgitation, cardiac surgery was performed: myxomatous degenerative mitral valve leaflets, failure of mitral valve cleft closure and anomalous coronary sinus communication to the left atrium (mimicking echocardiogram findings of suspected empty abscess cavity) were observed. Thus mitral valve replacement using a biological valve prosthesis was performed. Macroscopically there was no evidence of endocarditis, confirming PET/CT scan results. During the post–surgery period, third–degree atrioventricular block episodes were noted. Therefore a bicameral pacemaker was implanted. Conclusions This case report demonstrates the importance of not stopping at the first impression, as failure of previous mitral valve repair in a patient presented with persistent fever can mimic endocarditis. Therefore, the results of diagnostic tests should be compared to patients’ medical history and their clinical presentation.

Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and non-recovery in ACLF. Here we mapped the single-cell transcriptome of circulating immune cells from ACLF-, acute decompensated (AD) cirrhosis patients and healthy individuals. We further interrogate how these findings as well as immunometabolic- and functional profiles associate with ACLF recovery (ACLF-R) or non-recovery (ACLF-NR). Our analysis unveiled two distinct states of classical monocytes (cMon). Hereto, ACLF-R cMons were characterized by transcripts associated with immune- and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1. Additional metabolomic- and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program and blunted activation among lymphoid populations in ACLF-R patients. Conversely, ACLF-NR cMon featured elevated expression of inflammatory- and stress response genes such as VIM, LGALS2, and TREM1 along with blunted metabolic activity and increased functionality. This study identifies distinct immuno-metabolic cellular states that contribute to disease outcome in ACLF patients. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or non-recovery phenotypes which may be harnessed as potential therapeutic targets in the future.

Phosphorylation-amplified synchronized droplet microfluidics sensitizes bacterial growth kinetic real-time monitoring

The necessity for rapid and accurate bacterial growth monitoring is imperative across various domains, including healthcare and environmental safety. We introduce the self-synchronized droplet-amplified electrical screening cytometry (SYNC) system, a novel meld of droplet microfluidics and electrochemical amplification tailored for precise bacterial growth kinetic monitoring. SYNC encapsulates single bacteria in picolitre droplets, enabling real-time, fluorescence-free electrochemical monitoring. A specially devised phosphorylation-amplified culture medium translates bacterial metabolic activity into discernible electrical impedance changes. The dual-channel design and a rail-based structure in SYNC facilitate parallel screening and self-synchronization of droplets, addressing the limitations of conventional impedance cytometry. SYNC showcases a 5-fold enhancement in detection sensitivity and reduces 50% of the detection time compared to traditional approaches. Notably, SYNC is pioneering in providing exact initial bacterial concentrations, achieve to 104 bacteria/ml, a capability unmatched by existing real-time techniques measuring electrochemical variations. Along with its robust performance, this earmarks SYNC as a powerful tool for applications such as antibiotic susceptibility testing, food quality monitoring, and real-time water bacteria monitoring, paving the way for enhanced microbial process management and infection control.

Biological clock regulation by the PER gene family: a new perspective on tumor development

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.