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Trichoderma reesei strain Rut-C30 was modified with enhanced beta-glycosidase (BGL) activity to balance the cellulase system and generated laccase (LAC) protein for lignin degradation. Initially, the binary plasmid p1300-w1 was constructed to express T. reesei bgl2 under the control of promoter P pki and T-nos terminator. Random insertion was performed via Agrobacterium tumefaciens-mediated transformation. A total of 353 mutants were obtained, and 34PTrb2 was exceptionally stable with increased FPA and BGL activity after screening for extracellular enzyme activity. Subsequently, 34PTrb2 was used as parent strain via the same method to insert the lac gene from Fomes lignosus, with promoter P gpd , followed by cbh1 signal peptide trss and T-nos as terminator. Several mutants successfully expressed enzyme LAC with stable activity of approximately 0.13 U/mL. The mutant 15Gsslac increased activity by 40.4% FPA compared with that of the host Rut-C30.

This work explored the feasibility of paper waste (PW)/sewage sludge (SS) co-fermentation for volatile fatty acids (VFAs) production, and disclosed its correlation with the key operational parameters (i.e., pH and PW/SS ratio). The results indicated that the maximal VFAs was 251.55 mg COD/g TSS at optimal conditions, which was approximately 10-folds of sole SS fermentation. PW feeding contributed to the bioavailable substrates and C/N balance during co-fermentation process. The pH exhibited evident impacts on organics solubilization/hydrolysis, in which acidic pH was more beneficial for carbohydrates metabolism while alkaline pH was better for proteins. Under optimal operational conditions, the metabolic functions associated with VFAs production (i.e., substrate membrane transport, intracellular metabolism and VFAs biosynthesis) were up-regulated. Moreover, functional microorganisms (i.e., Saccharofermentans and Bacteroides) responsible for VFAs generation were enriched. This work provided an innovative approach to recovery valuable products from biowastes, and in-depth understandings of microbial features in PW/SS co-fermentation systems.

Paper mill sludge (PS), a solid waste from pulp and paper industry, was investigated as a feedstock for acetone-butanol-ethanol (ABE) production by simultaneous saccharification and fermentation (SSF). ABE fermentation of paper sludge by Clostridium acetobutylicum required partial removal of ash in PS to enhance its enzymatic digestibility. Enzymatic hydrolysis was found to be a rate-limiting step in the SSF. A total of 16.4-18.0g/L of ABE solvents were produced in the SSF of de-ashed PS with solid loading of 6.3-7.4% and enzyme loading of 10-15FPU/g-glucan, and the final solvent yield reached 0.27g/g sugars. No pretreatment and pH control were needed in ABE fermentation of paper sludge, which makes it an attractive feedstock for butanol production. The results suggested utilization of paper sludge should not only consider the benefits of buffering effect of CaCO3 in fermentation, but also take into account its inhibitory effect on enzymatic hydrolysis.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that - potentially severe - side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease. ispartof: CLINICAL AND TRANSLATIONAL ALLERGY vol:10 issue:1 ispartof: location:England status: published

Anthropogenic activities are altering levels of atmospheric carbon dioxide (CO2) and tropospheric ozone (O3). These changes can alter phytochemistry, and in turn, influence ecosystem processes. We assessed the individual and combined effects of elevated CO2 and O3 on the phytochemical composition of two tree species common to early successional, northern temperate forests. Trembling aspen (Populus tremuloides) and paper birch (Betula papyrifera) were grown at the Aspen FACE (Free-Air Carbon dioxide and ozone Enrichment) facility under four combinations of ambient and elevated CO2 and O3. We measured, over three years (2006-08), the effects of CO2 and O3 on a suite of foliar traits known to influence forest functioning. Elevated CO2 had minimal effect on foliar nitrogen and carbohydrate levels in either tree species, and increased synthesis of condensed tannins and fiber in aspen, but not birch. Elevated O3 decreased nitrogen levels in both tree species and increased production of sugar, condensed tannins, fiber, and lignin in aspen, but not birch. The magnitude of responses to elevated CO2 and O3 varied seasonally for both tree species. When co-occurring, CO2 offset most of the changes in foliar chemistry expressed under elevated O3 alone. Our results suggest that levels of CO2 and O3 predicted for the mid-twenty-first century will alter the foliar chemistry of northern temperate forests with likely consequences for forest community and ecosystem dynamics.

HCC has remained one of the challenging cancers to treat, owing to the paucity of drugs targeting the critical survival pathways. Considering the cancer cells are deficient in DNase activity, the increase of an autonomous apoptisis endonuclease should be a reasonable choice for cancer treatment. In this study, we investigated whether DNASE1L3, an endonuclease implicated in apoptosis, could inhibit the progress of HCC. We found DNASE1L3 was down-regulated in HCC tissues, whereas its high expression was positively associated with the favorable prognosis of patients with HCC. Besides, serum DNASE1L3 levels were lower in HCC patients than in healthy individuals. Functionally, we found that DNASE1L3 inhibited the proliferation of tumor cells by inducing G0/G1 cell cycle arrest and cell apoptosis in vitro. Additionally, DNASE1L3 overexpression suppressed tumor growth in vivo. Furthermore, we found that DNASE1L3 overexpression weakened glycolysis in HCC cells and tissues via inactivating the rate-limiting enzymes involved in PTPN2-HK2 and CEBPβ-p53-PFK1 pathways. Finally, we identified the HBx to inhibit DNASE1L3 expression by up-regulating the expression of ZNF384. Collectively, our findings demonstrated that DNASE1L3 could inhibit the HCC progression through inducing cell apoptosis and weakening glycolysis. We believe DNASE1L3 could be considered as a promising prognostic biomarker and therapeutic target for HCC.

Key points Paternal obesity negatively influences metabolic outcomes in adult rat offspring.Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers.Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring.Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers.This paper presents a feasible, low‐cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity. Abstract We investigated whether maternal exercise before and during gestation could attenuate the negative metabolic effects of paternal high‐fat diet‐induced obesity in female adult rat offspring. Fathers consumed a normal chow or high‐fat diet before mating. Mothers exercised on a treadmill before and during gestation or remained sedentary. In adulthood, female offspring were assessed using intraperitoneal insulin and glucose tolerance tests (IPITT and IPGTT, respectively), pancreatic morphology, ex vivo skeletal muscle insulin‐stimulated glucose uptake and mitochondrial respiratory function. Paternal obesity impaired whole‐body and skeletal muscle insulin sensitivity and insulin secretion in adult offspring. Maternal exercise attenuated the lower insulin‐stimulated glucose uptake in offspring sired by obese fathers but distal insulin signalling components (p‐AKT Thr308 and Ser473, p‐TBC1D4 Thr642 and GLUT4) remained unchanged (P > 0.05). Maternal exercise increased citrate synthase activity only in offspring sired by obese fathers. Maternal exercise also reversed the lower insulin secretion in vivo observed in offspring of obese fathers, probably due to an attenuation of the decrease in pancreatic beta cell mass. In summary, maternal exercise before and during pregnancy in rats attenuated skeletal muscle insulin resistance and attenuated the decrease in pancreatic beta cell mass and insulin secretion observed in the female offspring of obese fathers., Key points Paternal obesity negatively influences metabolic outcomes in adult rat offspring.Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers.Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring.Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers.This paper presents a feasible, low‐cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity.

Metallothionein (MT) is a family of low molecular weight, cysteine-rich proteins that regulate zinc homeostasis and have potential protective effects against oxidative stress and toxic metals. MT1 and MT2 gene knockout (MTKO) mice show shorter lifespans than wild-type (WT) mice. In this study, we aimed to investigate how MT gene deficiency accelerates aging. We performed comparative metabolomic analyses of plasma between MTKO and WT male mice at middle age (50-week-old) and advanced age (100-week-old) using liquid chromatography with time-of-flight mass spectrometry (LC-TOF-MS). The concentration of N6,N6,N6-trimethyl-L-lysine (TML), which is a metabolic intermediate in carnitine biosynthesis, was consistently higher in the plasma of MTKO mice compared to that of WT mice at middle and advanced age. Quantitative reverse transcription PCR (RT-PCR) analysis revealed remarkably lower mRNA levels of Tmlhe, which encodes TML dioxygenase, in the liver and kidney of male MTKO mice compared to that of WT mice. L-carnitine is essential for β-oxidation of long-chain fatty acids in mitochondria, the activity of which is closely related to aging. Our results suggest that reduced carnitine biosynthesis capacity in MTKO mice compared to WT mice led to metabolic disorders of fatty acids in mitochondria in MTKO mice, which may have caused shortened lifespans.

The discarding and burning of corn stalks in the fields after harvesting lead to environmental pollution and waste of resources. Composting is an effective way to disposal of the crop straws. Composting is a complex biochemical process and needs a detailed study in cold region. Hence, the succession process of bacteria and Actinomycetes in the process of corn stalk composting in cold region was studied by 16SrRNA. Alpha diversity analysis showed that the detection results could represent the real situation. The bacterial community diversity from high to low was F50 > F90 > F0 > F10 > F20. The results of beta analysis showed that F20 and F50 had the most similar microbial structure at the phylum level, and the difference between F0 and F20 was the largest. The dominant microbes changed from Proteobacteria and Bacteroidetes in F0 in heating stage to Firmicutes and Proteobacteria, Actinobacteria and Firmicutes in F10 during early high temperature stage, and Actinobacteria, Proteobacteria and Bacteroidetes in cooling and post composting phases. Actinobacteria and Firmicutes were the dominant bacteria in the whole composting process. In the composting process, the microbial community was mainly involved in amino acid metabolism related to nitrogen transformation and carbohydrate metabolism related to lignocellulose degradation. Lignin and hemicellulose were mainly degraded in thermophilic stage. The conversion of nitrogen and degradation of cellulose occurred mainly in the early stages of composting. The research will be helpful to understand the biochemical process of composting in cold region.

Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n= 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS (n= 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate

Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

Objective Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) uses the host's angiotensin-converting enzyme 2 (ACE2) as a cellular entry point. Therefore, modulating ACE2 might impact SARS-CoV-2 viral replication, shedding, and coronavirus disease 2019 (COVID-19) severity. Here, it was investigated whether the angiotensin II type 1 receptor blocker valsartan alters the expression of renin-angiotensin system (RAS) components, including ACE2, in human adipose tissue (AT) and skeletal muscle. Methods A randomized, double-blind, placebo-controlled clinical trial was performed, in which 36 participants (BMI 31.0 +/- 0.8 kg/m(2)) with impaired glucose metabolism received either valsartan or placebo for 26 weeks. Before and after 26 weeks' treatment, abdominal subcutaneous AT and skeletal muscle biopsies were obtained, and gene expression of RAS components was measured by quantitative reverse transcription polymerase chain reaction. Results Valsartan treatment did not significantly impact the expression of RAS components, including ACE2, in AT and skeletal muscle. Conclusions Given the pivotal role of ACE2 in SARS-CoV-2 spread and the clinical outcomes in COVID-19 patients, the data suggest that the putative beneficial effects of angiotensin II type 1 receptor blockers on the clinical outcomes of patients with COVID-19 may not be mediated through altered ACE2 expression in abdominal subcutaneous AT.

Cancer is a highly malignant disease, killing approximately 10 million people worldwide in 2020. Cancer patient survival substantially relies on early diagnosis. In this study, we evaluated whether genes involved in glucose metabolism could be used as potential diagnostic markers for cancer. In total, 127 genes were examined for their gene expression levels and pairwise gene correlations. Genes ADH1B and PDHA2 were differentially expressed in most of the 12 types of cancer and five pairs of genes exhibited consistent correlation changes (from strong correlations in normal controls to weak correlations in cancer patients) across all types of cancer. Thus, the two differentially expressed genes and five gene pairs could be potential diagnostic markers for cancer. Further preclinical and clinical studies are warranted to prove whether these genes and/or gene pairs would indeed aid in early diagnosis of cancer.

Ameliorating hyperglycemia and insulin resistance are major therapeutic strategies for type 2 diabetes. Previous studies have indicated that photobiomodulation therapy (PBMT) attenuates metabolic abnormalities in insulin-resistant adipose cells and tissues. However, it remains unclear whether PBMT ameliorates glucose metabolism in skeletal muscle in type 2 diabetes models. Here we showed that PBMT reduced blood glucose and insulin resistance, and reversed metabolic abnormalities in skeletal muscle in two diabetic mouse models. PBMT accelerated adenosine triphosphate (ATP) and reactive oxygen species (ROS) generation by elevating cytochrome c oxidase (CcO) activity. ROS-induced activation of phosphatase and tensin homolog (PTEN)/ protein kinase B (AKT) signaling after PBMT promoted glucose transporter GLUT4 translocation and glycogen synthase (GS) activation, accelerating glucose uptake and glycogen synthesis in skeletal muscle. CcO subunit III deficiency, ROS elimination, and AKT inhibition suppressed the PBMT effects of glucose metabolism in skeletal muscle. This study indicated amelioration of glucose metabolism after PBMT in diabetic mouse models and revealed the metabolic regulatory effects and mechanisms of PBMT on skeletal muscle.

Hypochlorous acid (HOCl) is generated at a high concentration by activated neutrophils at sites of inflammation in a myeloperoxidase catalyzed reaction. The increased and sustained production of HOCl at inflammatory sites may lead to tissue injury and this process is believed to play an important role in the progression of several diseases like chronic inflammation, atherosclerosis and some types of cancers. We have examined the effect of HOCl on human red blood cells (RBCs) under in vitro conditions. Treatment of RBC with different concentrations of HOCl (0.05–2.5 mM) at 37°C resulted in decreased activities of major antioxidant enzymes while the antioxidant power of RBC was weakened, as shown by lowered metal-reducing and free radical quenching ability of HOCl treated cells. RBC plasma membrane redox system was also inhibited suggesting membrane damage. The enzymes of glucose metabolism were inhibited indicating deranged energy metabolism. Electron microscopic images showed gross morphological changes in HOCl treated RBC. These results show that HOCl causes major alterations in the cellular antioxidant defense system and inhibition of glycolytic pathways, which increase the susceptibility of RBC to oxidative damage.

Background: Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes. Methods: We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in. Results: We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients. Conclusion: These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.

The global incidence of ulcerative colitis (UC) continues to increase while it’s clinical cure rate remains low. Intestinal mucosal ulcers have segmental distribution and variable severity. Intestinal bacteria are closely related to intestinal immunity and metabolism; however, the relationship between intestinal microbiome profile and the occurrence of UC, as well as the contribution of glucose metabolism, are not well understood. This was investigated in the present study using mucosal biopsies from patients with UC and healthy control subjects. We performed high throughput 16S rRNA gene sequencing to estimate microbiota composition and abundance as well as their association with clinical indices such as lesion severity. The results showed that the diversity and abundance of intestinal microbiota were significantly lower in patients with UC than in healthy subjects; however, these were unrelated to ulcer severity. Serum glucagon-like peptide 2 (GLP-2) level was associated with reduced microbiota diversity and abundance in UC. These results indicate that colonization by specific microbiota is not the main determinant of pathologic status in UC. Additionally, therapeutic strategies that increase GLP-2 levels in intestinal mucosa may be effective in the treatment of UC., Graphical abstract

International audience; Background: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.Methods: In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

Identifying cerebral vulnerability in late life may help prevent or slow the progression of aging-related chronic diseases. However, non-invasive biomarkers aimed at detecting subclinical cerebral changes in the elderly are lacking. Here, we have examined the potential of plasma total tau (t-tau) for identifying cerebral and cognitive deficits in normal elderly subjects. Patterns of cortical thickness and cortical glucose metabolism were used as outcomes of cerebral vulnerability. We found that increased plasma t-tau levels were associated with widespread reductions of cortical glucose uptake, thinning of the temporal lobe, and memory deficits. Importantly, tau-related reductions of glucose consumption in the orbitofrontal cortex emerged as a determining factor of the relationship between cortical thinning and memory loss. Together, these results support the view that plasma t-tau may serve to identify subclinical cerebral and cognitive deficits in normal aging, allowing detection of individuals at risk for developing aging-related neurodegenerative conditions.

Accumulating evidence from epidemiological studies of humans and genetic models in rodents has shown that offspring from males of advanced paternal age (APA) are susceptible to metabolic and neurological disorders. However, knowledge of molecular mechanism(s) underlying these metabolic and behavioral changes at the intergeneration and trans-generation levels from APA is limited. Here, we characterized changes on glucose and cholesterol metabolism, and also autism spectrum disorders (ASD)-like behaviors in 1st and 2nd generations from 12- and 18-month-old male mice, respectively. Whole Genome Bisulfite Sequencing (WGBS) of sperm from APA mice identified differentially methylated regions (DMRs) within the whole genome, and DMRs within promoter regions, suggesting that specific genes and relevant pathways might be associated with autism and aberrant glucose metabolism in the offspring from APA males. These results strongly suggest that epigenetic reprogramming induced by aging in male sperm may lead to high risks of aberrant glucose metabolism and the development of ASD behaviors in intergenerational and transgenerational offspring.

Antimicrobial peptides are considered to be one of the candidate antimicrobial agents for antibiotic-resistant bacterial infection in the future. The effects of antimicrobial peptide hBD3-CBD on Pseudomonas aeruginosa PA14 and PA14 ΔexsA were analyzed by the bactericidal effects, hemolysis assays, pyocyanin pigment productions, and virulence factor expressions (exoU, exoS, hcnA, and lasB). Pyocyanin production and virulence factor expressions are important features of the type III secretion system in Pseudomonas aeruginosa. HBD3-CBD killed PA14 and PA14 ΔexsA with similar efficiency; it lowered the hemolysis levels of PA14 and PA14 ΔexsA and reduced the pyocyanin production, biofilm formation, and exoU, exoS, and lasB expressions in PA14. Compared with PA14, PA14 ΔexsA showed a lower hemolysis effect, pyocyanin production, exoU, and lasB expressions. The effects of hBD3-CBD on the PA14 toxin secretion were similar to the changes in the type III secretion system mutant isolate PA14 ΔexsA. Our results demonstrated that the type III secretion system was involved in the biological functions on PA 14 from hBD3-CBD.

Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor in the connection between glycolysis and the tricarboxylic acid cycle. Restoring the mitochondrial OXPHOS function by inhibiting glycolysis through targeting PDK1 has become a hot spot for tumor therapy. However, the specific mechanism by which metabolic changes affect mitochondrial function remains unclear. Recent studies have found that mitochondrial quality control such as mitochondrial protein homeostasis plays an important role in maintaining mitochondrial function. Here, we focused on PDK1 and explored the specific mechanism by which metabolic changes affect mitochondrial OXPHOS function. We showed that glucose metabolism in HepG2 and HepG3B cells switched from anaerobic glycolysis to the mitochondrial tricarboxylic acid cycle under different concentrations of dichloroacetate (DCA) or short hairpin PDK1. After DCA treatment or knockdown of PDK1, the mitochondrial morphology was gradually condensed and exhibited shorter and more fragmented filaments. Additionally, expression of the mitochondrial autophagy proteins parkin and PTEN-induced kinase was down-regulated, and the biosynthetic protein peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and its regulated complex I, III, IV, and V protein were down-regulated. This indicated that PDK1 inhibition affected the level of mitochondrial quality control. Analysis of mitochondrial function revealed significantly increased mitochondrial reactive oxygen species and decreased membrane potential. Therefore, glucose metabolism reprogramming by PDK1 inhibition could induce mitochondrial quality control disorders to aggravate mitochondrial stress damage.

Deregulation of aerobic glycolysis is a common phenomenon in human cancers, including glioblastoma (GBM). In the present study, we demonstrated that the natural compound xanthohumol has a profound anti-tumor effect on GBM via direct inhibition of glycolysis. Xanthohumol suppressed cell proliferation and colony formation of GBM cells, and significantly impaired glucose metabolism via inhibiting Hexokinase 2 (HK2) expression. We demonstrated that down-regulation of c-Myc was required for xanthohumol-induced decrease of HK2. Xanthohumol destabilization of c-Myc, and promoted FBW7-mediated ubiquitination of c-Myc. Xanthohumol attenuated Akt activity and inhibited the activation of GSK3β, resulted in c-Myc degradation. Overexpression of Myr-Akt1 significantly rescued xanthohumol-mediated c-Myc inhibition and glycolysis suppression. Finally, the xanthohumol-mediated down-regulation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis promoted the destabilization of c-Myc. Finally, the animal results demonstrated that xanthohumol substantially inhibited tumor growth in vivo. Collectively, xanthohumol appears to be a promising new anti-tumor agent with the therapeutic potential for GBM.

Background: Osteocalcin is related to energy metabolism, memory and the acute stress response, suggesting a relationship between bone and the brain. The need to explore the effect of osteocalcin on acute ischemic stroke is therefore urgent. Results: Patients with better outcomes had higher serum osteocalcin levels than those whose NIHSS scores did not improve. Multivariable logistic regression analysis showed acceptable performance (area under the curve = 0.766). The effect of osteocalcin on the promotion of neuron survival was confirmed by Cell Counting Kit-8 experiments. In addition, osteocalcin could decrease proline hydroxylase 1 and inhibit the degradation of gasdermin D. Conclusions: We propose that osteocalcin can improve outcome after acute ischemic stroke in the acute period. By downregulating proline hydroxylase 1, osteocalcin leads glucose metabolism to the pentose phosphate pathway and therefore promotes neuronal survival through inhibiting pyroptosis. Methods: Demographic data and laboratory results were obtained from patients with ischemic stroke in the acute period for analysis. A receiver operating characteristic curve was used to assess the discrimination of the prediction model. The potential effect of osteocalcin on cerebral ischemia and osteocalcin mechanism were explored in cultured primary rat cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation.

Adipose tissue is an important metabolic organ, and transplantation of white adipose tissue plays crucial roles in glucose homoeostasis and energy metabolism. However, how adipose tissue affects glucose utilization is poorly understood. PAI-1-knockout (PAI-1KO) mice were previously shown to be resistant to a high-fat diet and obesity. We used microPET/CT (positron emission tomography/computed tomography), gene microarray, and biochemical assays to measure changes in systemic and myocardial glucose metabolism in mice subjected to transplantation of adipose tissue from PAI-1KO and wild-type mice. Here, we show that transplanting subcutaneous white adipose tissue (scWAT) from PAI-1KO mice into high-fat diet (HFD)-fed mice reduced levels of serum total cholesterol and triglycerides, and improved glucose tolerance in the HFD-fed mice. microPET/CT imaging revealed that cardiac glucose uptake was increased in the heart but not in the liver, hindlimb muscles, or abdominal subcutaneous white adipose tissue in HFD-fed mice transplanted with PAI-1KO scWAT, suggesting that the transplanted PAI-1KO scWAT exerted endocrine effects in the heart. In addition, transplantation of scWAT from PAI-1KO mice upregulated mitochondrial gene expression in cardiac muscle, increased the expression of glucose transporters 1 and 4 in cardiac tissues and was associated with an increased NAD+/NADH ratio. Together, these findings suggest that modulating PAI-1 in scWAT may provide a promising approach for intervening in glucose metabolism.

Background: Vitamin A (VA) plays an essential role in pancreatic homeostasis. Islet stellate cells (ISCs) are VA-storing cells in pancreatic islets. Herein, we have investigated the effect of VA on glucose homeostasis trough regulation of ISCs function in dietary VA deficiency model mice. Methods: Male C57BL/6 mice were randomly fed a VA-sufficient, a VA-deficient (VAD) or a VAD-rescued diet. Glucose metabolism was assessed by glucose tolerance tests and immunohistochemistry. ISCs activation degree was evaluated by immunofluorescence, quantitative PCR and western blotting in both, retinol-treated cultured ISCs and model mice. Changes in ISCs phenotype and their effect on islets were assessed by lentiviral transduction and enzyme-linked immunosorbent assays in a co-culture system. Results: VAD mice showed irregular shaped islet, glucose intolerance, islet size distribution excursions, and upregulated expression of α-smooth muscle actin (α-SMA, marker of ISCs activation). Reintroduction of dietary VA restored pancreatic VA levels, endocrine hormone profiles, and inhibited ISCs activation. Incubation with retinol increased the expression of VA signaling factors in ISCs, including cellular retinol binding protein 1 (CRBP1). The knockdown of CRBP1 maintained the quiescent ISCs phenotype and reduced the damage of activated ISCs on islet function. Conclusions: VA deficiency reduced islet function by activating ISCs in VAD mice. Restoring ISCs quiescence via CRBP1 inhibition could reverse the impairment of islet function caused by activated ISCs exposure.

The journal of experimental botany 71(4), 1628 - 1644 (2020). doi:10.1093/jxb/erz530, Solving the global environmental and agricultural problem of chronic low-level cadmium (Cd) exposure requires better mechanistic understanding. Here, soybean (Glycine max) plants were exposed to Cd concentrations ranging from 0.5 nM (background concentration, control) to 3 µM. Plants were cultivated hydroponically under non-nodulating conditions for 10 weeks. Toxicity symptoms, net photosynthetic oxygen production and photosynthesis biophysics (chlorophyll fluorescence: Kautsky and OJIP) were measured in young mature leaves. Cd binding to proteins [metalloproteomics by HPLC-inductively coupled plasma (ICP)-MS] and Cd ligands in light-harvesting complex II (LHCII) [X-ray absorption near edge structure (XANES)], and accumulation of elements, chloropyll, and metabolites were determined in leaves after harvest. A distinct threshold concentration of toxicity onset (140 nM) was apparent in strongly decreased growth, the switch-like pattern for nutrient uptake and metal accumulation, and photosynthetic fluorescence parameters such as Φ RE10 (OJIP) and saturation of the net photosynthetic oxygen release rate. XANES analyses of isolated LHCII revealed that Cd was bound to nitrogen or oxygen (and not sulfur) atoms. Nutrient deficiencies caused by inhibited uptake could be due to transporter blockage by Cd ions. The changes in specific fluorescence kinetic parameters indicate electrons not being transferred from PSII to PSI. Inhibition of photosynthesis combined with inhibition of root function could explain why amino acid and carbohydrate metabolism decreased in favour of molecules involved in Cd stress tolerance (e.g. antioxidative system and detoxifying ligands)., Published by Oxford Univ. Press, Oxford

Black rockfish (Sebastes schlegelii) is an economically important viviparous marine teleost in Japan, Korea, and China. It is characterized by internal fertilization, long-term sperm storage in the female ovary, and a high abortion rate. For better understanding the mechanism of fertilization and gestation, it is essential to establish a reference genome for viviparous teleosts. Herein, we used a combination of Pacific Biosciences sequel, Illumina sequencing platforms, 10× Genomics, and Hi-C technology to obtain a genome assembly size of 848.31 Mb comprising 24 chromosomes, and contig and scaffold N50 lengths of 2.96 and 35.63 Mb, respectively. We predicted 39.98% repetitive elements, and 26,979 protein-coding genes. S. schlegelii diverged from Gasterosteus aculeatus ∼32.1-56.8 million years ago. Furthermore, sperm remained viable within the ovary for up to 6 months. The glucose transporter SLC2 showed significantly positive genomic selection, and carbohydrate metabolism-related KEGG pathways were significantly up-regulated in ovaries after copulation. In vitro suppression of glycolysis with sodium iodoacetate reduced sperm longevity significantly. The results indicated the importance of carbohydrates in maintaining sperm survivability. Decoding the S. schlegelii genome not only provides new insights into sperm storage; additionally, it is highly valuable for marine researchers and reproduction biologists.

Background and purpose Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use. Experimental approach Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice. Key results Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream β oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells. Conclusion and implications Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD.

Background: End-induction minimal residual disease (MRD) is the strongest predictor of relapse in paediatric acute lymphoblastic leukaemia (ALL), but an understanding of the biological pathways underlying early treatment response remains elusive. We hypothesized that metabolomic profiling of diagnostic bone marrow plasma could provide insights into the underlying biology of early treatment response and inform treatment strategies for high-risk patients. Methods: We performed global metabolomic profiling of samples from discovery (N = 93) and replication (N = 62) cohorts treated at Texas Children's Hospital. Next, we tested the cytotoxicity of drugs targeting central carbon metabolism in cell lines and patient-derived xenograft (PDX) cells. Findings: Metabolite set enrichment analysis identified altered central carbon and amino acid metabolism in MRD-positive patients from both cohorts at a 5% false discovery rate. Metabolites from these pathways were used as inputs for unsupervised hierarchical clustering. Two distinct clusters were identified, which were independently associated with MRD after adjustment for immunophenotype, cytogenetics, and NCI risk group. Three nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which reduce glycolytic/TCA cycle activities, demonstrated nanomolar-range cytotoxicity in B- and T-ALL cell lines and PDX cells. Interpretation: This study provides new insights into the role of central carbon metabolism in early treatment response and as a potential targetable pathway in high-risk disease. Funding: American Society of Hematology; Baylor College of Medicine Department of Paediatrics; Cancer Prevention and Research Institute of Texas; the Lynch family; St. Baldrick's Foundation with support from the Micaela's Army Foundation; United States National Institutes of Health. Keywords: Acute lymphoblastic leukaemia, Minimal residual disease, Epidemiology, NAMPT, NAMPT inhibitors

Lately there are many new, promising low-density lipoprotein cholesterol reducing therapies with PCSK9 inhibitors. We performed selected sampling of the publications in PubMed and made a review according to selected keywords. It summarizes the effect of PCSK9 on vascular aging, directly associated with lipid and glucose metabolism, chronic inflammation, atherosclerosis and hypertension. Serum level of PCSK9 is different in patients affected by certain illnesses (whose risk increases with age) than in healthy individuals. The same could be observed in the case of chronic inflammation. In this review we summarize what is known about the role PCSK9 in human metabolism and how this could affect the vascular aging process. Based on the available sources, we prove that PCSK9 is involved in many biochemical pathways associated with vascular aging. In the future, treatments using PCSK9 inhibition may not only reduce the cardiovascular risk but also slow down this process.Ostatnio pojawiła się nowa metoda redukcji stężenia cholesterolu LDL z wykorzystaniem inhibitorów PCSK9. Na podstawie przeglądu piśmiennictwa dostępnego w bazie PubMed podsumowano wiedzę na temat związku białka PCSK9 z procesami starzenia naczyń krwionośnych. Procesy te są bezpośrednio powiązane z metabolizmem lipidów i glukozy, przewlekłym stanem zapalnym, miażdżycą, a także nadciśnieniem tętniczym. Zebrane dane wskazują na różnice w stężeniach białka PCSK9 w osoczu między osobami zdrowymi a osobami dotkniętymi określonymi chorobami występującymi w starszym wieku. Ta sama zależność występuje w przypadku przewlekłego stanu zapalnego. W niniejszej pracy podsumowano wiedzę na temat roli PCSK9 w metabolizmie człowieka, przedstawiając szlaki biochemiczne z udziałem tego białka, które oddziałują na proces starzenia naczyń krwionośnych. Na podstawie dostępnych źródeł autorzy wskazują na istotną rolę PCSK9 w szlakach biochemicznych zaangażowanych w ten proces. Przypuszcza się, że leczenie z zastosowaniem inhibicji PCSK9 będzie skutkować nie tylko zmniejszeniem ryzyka rozwoju chorób układu krążenia, lecz także spowolnieniem procesu starzenia naczyń krwionośnych.

Background & aims Plasma concentrations of bilirubin, a product of heme catabolism formed by biliverdin reductase A (BVRA), inversely associate with the risk of metabolic diseases including hepatic steatosis and diabetes mellitus in humans. Bilirubin has antioxidant and anti-inflammatory activities and may also regulate insulin signaling and peroxisome proliferator-activated receptor alpha (PPARα) activity. However, a causal link between bilirubin and metabolic diseases remains to be established. Here, we used the global Bvra gene knockout (Bvra–/–) mouse as a model of deficiency in bilirubin to assess its role in metabolic diseases. Approach & results We fed mice fat-rich diets to induce hepatic steatosis and insulin resistance. Bile pigments were measured by LC-MS/MS, and hepatic lipids by LC-MS/MS (non-targeted lipidomics), HPLC-UV and Oil-Red-O staining. Oxidative stress was evaluated measuring F2-isoprostanes by GC-MS. Glucose metabolism and insulin sensitivity were verified by glucose and insulin tolerance tests, ex vivo and in vivo glucose uptake, and Western blotting for insulin signaling. Compared with wild type littermates, Bvra–/– mice contained negligible bilirubin in plasma and liver, and they had comparable glucose metabolism and insulin sensitivity. However, Bvra–/– mice exhibited an inflamed and fatty liver phenotype, accompanied by hepatic accumulation of oxidized triacylglycerols and F2-isoprostanes, in association with depletion of α-tocopherol. α-Tocopherol supplementation reversed the hepatic phenotype and observed biochemical changes in Bvra–/– mice. Conclusions Our data suggests that BVRA deficiency renders mice susceptible to oxidative stress-induced hepatic steatosis in the absence of insulin resistance., Graphical abstract Image 1, Highlights • Low plasma levels of bilirubin associate with increased metabolic disease risk. • A direct link between bilirubin and metabolic disease remains to be established. • Global BVRA deficiency causes global bilirubin deficiency and a fatty, inflamed liver. • This hepatic phenotype is linked to decreased vitamin E and increased lipid oxidation. • Vitamin E supplements restore normal liver phenotype in BVRA deficiency.

Highlights • Acid-tolerant microalgae were grown at pH 3.5 and 6.7 in presence of heavy metals (HMs). • HMs-induced phenotypic changes in microalgae were evaluated by ATR-FTIR spectroscopy. • Higher HMs bioavailability affected microalgae more at pH 6.7 than pH 3.5. • Acclimation of microalgal strains to acidic pH significantly alleviates HMs toxicity., Acclimatory phenotypic response is a common phenomenon in microalgae, particularly during heavy metal stress. It is not clear so far whether acclimating to one abiotic stressor can alleviate the stress imposed by another abiotic factor. The intent of the present study was to demonstrate the implication of acidic pH in effecting phenotypic changes that facilitate microalgal tolerance to biologically excess concentrations of heavy metals. Two microalgal strains, Desmodesmus sp. MAS1 and Heterochlorella sp. MAS3, were exposed to biologically excess concentrations of Cu (0.50 and 1.0 mg L‒1), Fe (5 and 10 mg L‒1), Mn (5 and 10 mg L‒1) and Zn (2, 5 and 10 mg L‒1) supplemented to the culture medium at pH 3.5 and 6.7. Chlorophyll autofluorescence and biochemical fingerprinting using FTIR-spectroscopy were used to assess the microalgal strains for phenotypic changes that mediate tolerance to metals. Both the strains responded to acidic pH by effecting differential changes in biochemicals such as carbohydrates, proteins, and lipids. Both the microalgal strains, when acclimated to low pH of 3.5, exhibited an increase in protein ( 1.5-fold). Strain MAS1 grown at pH 3.5 showed a reduction (1.5-fold) in carbohydrates while strain MAS3 exhibited a 17-fold increase in carbohydrates as compared to their growth at pH 6.7. However, lower levels of biologically excess concentrations of the selected transition metals at pH 6.7 unveiled positive or no effect on physiology and biochemistry in microalgal strains, whereas growth with higher metal concentrations at this pH resulted in decreased chlorophyll content. Although the bioavailability of free-metal ions is higher at pH 3.5, as revealed by Visual MINTEQ model, no adverse effect was observed on chlorophyll content in cells grown at pH 3.5 than at pH 6.7. Furthermore, increasing concentrations of Fe, Mn and Zn significantly upregulated the carbohydrate metabolism, but not protein and lipid synthesis, in both strains at pH 3.5 as compared to their growth at pH 6.7. Overall, the impact of pH 3.5 on growth response suggested that acclimation of microalgal strains to acidic pH alleviates metal toxicity by triggering physiological and biochemical changes in microalgae for their survival.

It is now well-established that the Gram-negative bacterium, Helicobacter pylori, causes gastritis in humans. In recent years it has become apparent that the so-called non-pylori Helicobacters, normally infecting pigs, cats, and dogs, may also be involved in human pathology via zoonotic transmission. Indeed, more than 30 species of non-pylori Helicobacters have been identified thus far. One such organism is Helicobacter canadensis, an emerging pathogen whose genome sequence was published in 2009. Given our long-standing interest in the biosynthesis of N-formylated sugars found in the O-antigens of some Gram-negative bacteria, we were curious as to whether H. canadensis produces such unusual carbohydrates. Here we demonstrate using both biochemical and structural techniques, that the proteins encoded by the HCAN_0198, HCAN_0204, and HCAN_0200 genes in H. canadensis, correspond to a 3,4-ketoisomerase, a pyridoxal 5'-phosphate aminotransferase, and an N-formyltransferase, respectively. For this investigation, five high-resolution X-ray structures were determined and the kinetic parameters for the isomerase and the N-formyltransferase were measured. Based on these data, we suggest that the unusual sugar, 3-formamido-3,6-dideoxy-d-glucose, will most likely be found in the O-antigen of H. canadensis. Whether N-formylated sugars found in the O-antigen contribute to virulence is presently unclear, but it is intriguing that they have been observed in such pathogens as Francisella tularensis, Mycobacterium tuberculosis, and Brucella melitensis. This article is protected by copyright. All rights reserved.

Cellulose has a long history dating back to ancient times in the evolution of humanity. It was a key material for basic needs, especially for the construction of shelters, paper making, which allowed our ancestors to perpetuate the valuable literary, philosophical or artistic works. In modern era, cellulose has acquired new dimensions of knowledge and scientific interest. This increased interest in cellulose is due to the need to exploit the still unknown resources that cellulose provides us, possibly due to the remarkable progress made lately in the field of fine characterization of the structure using sophisticated electron microscopes and other characterization techniques that have recently emerged. The growing demands of modern society in the direction of computerization and technology, have led the general interest to move from the classical writing paper to other types of "papers" that incorporates a high degree of ingenuity and intelligence, the so-called special papers, ranging from sensors, chips, motherboards, papers with a high degree of security, and many others. Among these, paper-based biosensors are of special interest, due to their high selectivity, simplicity, low price, and fast response. In this article we will review the new trends in the immobilization of biomolecules on various cellulose-based supports. In the first part, we will discuss the stages prior to the manufacture of a such support by specific chemical modification of the cellulosic substrate, followed by an overview of the most studied proteins, but also the most commonly used methods in monitoring protein adsorption on cellulosic substrates.

Cellulosic biomass represents a huge reservoir of renewable carbon, but converting it into useful products is challenging. Attempts to transfer cellulose degradation capability to industrially useful micro-organisms have met with limited success, possibly due to poorly understood synergy between multiple cellulases. This is best studied by co-expression of many combinations of cellulases and associated proteins. Here, we describe the development of a test platform based on Citrobacter freundii, a cellobiose-assimilating organism closely related to Escherichia coli. Standard E. coli cloning vectors worked well in Cit. freundii. Expression of cellulases CenA and Cex of Cellulomonas fimi in Cit. freundii gave recombinant strains which were able to grow at the expense of cellulosic filter paper or microcrystalline cellulose (Avicel) in a mineral medium supplemented with a small amount of yeast extract. Periodic physical agitation of the cultures was highly beneficial for growth at the expense of filter paper. This provides a test platform for the expression of combinations of genes encoding biomass-degrading enzymes to develop effective genetic cassettes for degradation of different biomass streams. Significance and Impact of the Study Biofuels have been shown to be the best sustainable and alternative source of fuel to replace fossil fuels. Of the different types of feedstocks used for producing biofuels, lignocellulosic biomass is the most abundant. Converting this biomass to useful products has met with little success. Different approaches are being used and microbial platforms are the most promising and sustainable method. This study shows that Citrobacter freundii is a better test platform than Escherichia coli for testing various combinations of cellulases for the development of microbial systems for biomass conversion.

The emergence of New Delhi metallo-beta-lactamase (NDM-1) has become a major health threat to clinical managements of gram-negative bacteria infections. A novel incompatibility group X3 plasmid (IncX3) pNDM-HN380 carrying bla(NDM-1) has recently been found to epidemiologically link with multiple geographical areas in China. In this paper, we studied the metabolic responses of host bacteria E. coli J53 upon introduction of pNDM-HN380. A reduction of bacterial motility was observed in J53/pNDM-HN380. We profiled the RNA repertoires of the transconjugants and found a downregulation of genes involved in flagella and chemotaxis metabolic pathways at logarithmic (log) phase. We also identified a novel intragenic region (IGR) small RNA plas2. The plasmid-transcribed sRNA IGR plas2 was further characterized as a regulator of fucRwhich controls the fucose metabolism. By knockdown of IGR plas2 using an antisense decoy, we managed to inhibit the formation of bacterial biofilm of the host. Our study demonstrated a potential way of utilizing plasmid-transcribed sRNA against infectious bacteria.

Exercise‐induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4 (IRF4) on skeletal muscle glycogen and subsequent regulation of exercise capacity. Skeletal muscle‐specific IRF4 knockout mice show normal body weight and insulin sensitivity, but better exercise capacity and increased glycogen content with unaltered triglyceride levels compared to control mice on chow diet. In contrast, mice overexpression of IRF4 displays decreased exercise capacity and lower glycogen content. Mechanistically, IRF4 regulates glycogen‐associated regulatory subunit protein targeting to glycogen (PTG) to manipulate glucose metabolism in skeletal muscle. Knockdown of PTG can reverse the effects imposed by the absence of IRF4 in vivo. These studies reveal a regulatory pathway including IRF4/PTG/glycogen synthesis on controlling exercise capacity., Muscle glycogen is critical for exercise‐induced fatigue. However, how glycogen is manipulated during exercise is not well‐known. Interferon regulatory factor 4 (IRF4) was induced by exercise. Mice without IRF4 specific in muscle show increased glycogen content pre‐exercise and subsequently affects exercise capacity. These studies reveal a feedback signaling pathway including IRF4/protein targeting to glycogen (PTG)/glycogen synthesis that controlling exercise capacity.