Design Principles and Mechanistic Understandings of Non-Noble-Metal Bifunctional Electrocatalysts for Zinc-Air Batteries.

Zinc-air batteries (ZABs) are promising energy storage systems because of high theoretical energy density, safety, low cost, and abundance of zinc. However, the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs. Therefore, feasible and advanced non-noble-metal electrocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction. In this review, we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field. Then, we discussed the working mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design, crystal structure tuning, interface strategy, and atomic engineering. We also included theoretical studies, machine learning, and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions. Finally, we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.

Pan-cancer integrated analysis of ANKRD1 expression, prognostic value, and potential implications in cancer.

There is substantial evidence demonstrating the crucial role of inflammation in oncogenesis. ANKRD1 has been identified as an anti-inflammatory factor and is related to tumor drug resistance. However, there have been no studies investigating the prognostic value and molecular function of ANKRD1 in pan-cancer. In this study, we utilized the TCGA, GTEx, GSCALite, ENCORI, CTRP, DAVID, AmiGO 2, and KEGG databases as well as R language, to explore and visualize the role of ANKRD1 in tumors. We employed the ROC curve to explore its diagnostic significance, while the Kaplan-Meier survival curve and Cox regression analysis were used to investigate its prognostic value. Additionally, we performed Pearson correlation analysis to evaluate the association between ANKRD1 expression and DNA methylation, immune cell infiltration, immune checkpoints, TMB, MSI, MMR, and GSVA. Our findings indicate that ANKRD1 expression is dysregulated in pan-cancer. The ROC curve revealed that ANKRD1 expression is highly sensitive and specific in diagnosing CHOL, LUAD, LUSC, PAAD, SKCM, and UCS (AUC > 85.0%, P < 0.001). Higher ANKRD1 expression was related to higher overall survival (OS) in LGG, but with lower OS in COAD and STAD (P < 0.001). Moreover, Cox regression and nomogram analyzes suggested that ANKRD1 is an independent factor for COAD, GBM, HNSC, and LUSC. Dysregulation of ANKRD1 expression in pan-cancer involves DNA methylation and microRNA regulation. Using the CTRP database, we discovered that ANKRD1 may influence the half-maximal inhibitory concentration (IC50) of several anti-tumor drugs. ANKRD1 expression showed significant correlations with immune cell infiltration (including cancer-associated fibroblast and M2 macrophages), immune checkpoints, TMB, MSI, and MMR. Furthermore, ANKRD1 is involved in various inflammatory and immune pathways in COAD, GBM, and LUSC, as well as cardiac functions in HNSC. In vitro experiments demonstrated that ANKRD1 promotes migration, and invasion activity, while inhibiting apoptosis in colorectal cancer cell lines (Caco2, SW480). In summary, ANKRD1 represents a potential prognostic biomarker and therapeutic target in human cancers, particularly in COAD.

Boosting anaerobic digestion of long chain fatty acid with microbial electrolysis cell combining metal organic framework as cathode: Biofilm construction and metabolic pathways.

The role of metal organic framework (MOF) modified cathode in promoting long chain fatty acid (LCFA) methanation was identified in microbial electrolysis cell coupled anaerobic digestion (MEC-AD) system. The maximum methane production rate of MEC-AD-MOF achieved 49.8 ± 3.4 mL/d, which increased by 41 % compared to MEC-AD-C. The analysis of bio-cathode biofilm revealed that microbial activity, distribution, population, and protein secretion prompted by MOF cathode, which in turn led to an acceleration of electron transfer between the cathode and microbes. Specifically, the relative abundance of acetate-oxidizing bacterium (Mesotoga) in MEC-AD-MOF was 1.5-3.6 times higher than that in MEC-AD-C, with a co-metabolized enrichment of Methanobacterium. Moreover, MOF cathode reinforced LCFA methanation by raising the relative abundance of genes coded key enzymes involved in CO2-reducing pathway, and elevating the tolerance of microbes to LCFA inhibition. These results indicate that MOF can enhance biofilm construction in MEC-AD, thereby improving the treatment performance of lipid wastewater.

Preparation and Properties of GO/ZnO/nHAp Composite Microsphere Bone Regeneration Material.

The purpose of this study is to explore the possibility of using graphene-zinc oxide-hydroxyapatite (GO/ZnO/nHAp) composite microspheres as bone regeneration materials by making use of the complementary advantages of nanocomposites, so as to provide reference for the clinical application of preventing and solving bacterial infection after implantation of synthetic materials. Firstly, GO/ZnO composites and hydroxyapatite nanoparticles were synthesized using the hydrothermal method, and then GO/ZnO/nHAp composite microspheres were prepared via high-temperature sintering. The graphene-zinc oxide-calcium phosphate composite microspheres were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), energy dispersion spectroscopy (EDS), water contact angle measurement, degradation and pH determination, and differential thermal analysis (DiamondTG/DTA). The biocompatibility, osteogenic activity, and antibacterial activity of GO/ZnO/nHAp composite microspheres were further studied. The results of the cell experiment and antibacterial experiment showed that 0.5% and 1% GO-ZnO-nHAp composite microspheres not only had good biocompatibility and osteogenic ability but also inhibited Escherichia coli and Staphylococcus aureus by more than 45% and 70%. Therefore, GO/ZnO/nHAp composite microspheres have good physical and chemical properties and show good osteogenic induction and antibacterial activity, and this material has the possibility of being used as a bone regeneration material.

Recovery capability of anaerobic digestion from ammonia stress: Metabolic activity, energy generation, and genome-centric metagenomics.

Excessive ammonia stresses anaerobic digestion (AD) significantly. Although there has been progress in understanding AD under ammonia exposure, investigations on AD liberated from ammonia exposure are limited. Here, the recovery capability of AD from ammonia stress was evaluated, by examining specific methanogenic activity, energy-conserving capability, microbial community succession, and metabolic pathway reconstruction. The findings demonstrated that ammonia stress relief resulted in < 50% methane recovery, with propionate conversion identified as the critical impediment to AD reactivation. Energy generation could not recovered either. Efforts to mitigate ammonia stress failed to restore acetoclastic methanogens, e.g., Methanothrix soehngenii, and proved futile in awakening propionate oxidizers, e.g., Desulfobulbus. Interestingly, a symbiotic metabolism emerged, prevailing in stress-relieved AD due to its energy-conserving advantage. This study underscores the importance of targeted interventions, including stimulating acetoclastic methanogenesis, propionate oxidation, and energy generation, as priorities for AD recovery following ammonia stress, rather than focusing solely on ammonia level management.

Genome-wide transcription landscape of citric acid producing Aspergillus niger in response to glucose gradient.

Aspergillus niger is the main industrial workhorse for global citric acid production. This fungus has complex sensing and signaling pathways to respond to environmental nutrient fluctuations. As the preferred primary carbon source, glucose also acts as a critical signal to trigger intracellular bioprocesses. Currently, however, there is still a knowledge gap in systems-level understanding of metabolic and cellular responses to this vital carbon source. In this study, we determined genome-wide transcriptional changes of citric acid-producing Aspergillus niger in response to external glucose gradient. It demonstrated that external glucose fluctuation led to transcriptional reprogramming of many genes encoding proteins involved in fundamental cellular process, including ribosomal biogenesis, carbon transport and catabolism, glucose sensing and signaling. The major glucose catabolism repressor creA maintained a stable expression independent of external glucose, while creB and creD showed significant downregulation and upregulation by the glucose increase. Notably, several high-affinity glucose transporters encoding genes, including mstA, were greatly upregulated when glucose was depleted, while the expression of low-affinity glucose transporter mstC was glucose-independent, which showed clear concordance with their protein levels detected by in situ fluorescence labeling assay. In addition, we also observed that the citric acid exporter cexA was observed to be transcriptionally regulated by glucose availability, which was correlated with extracellular citric acid secretion. These discoveries not only deepen our understanding of the transcriptional regulation of glucose but also shed new light on the adaptive evolutionary mechanism of citric acid production of A. niger.

Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway.

Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1ß, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis.

Exosomal circKIAA1797 Regulates Cell Progression and Glycolysis by Targeting miR-4429/PBX3 Pathway in Gastric Cancer.

In recent years, circular RNAs (circRNAs) are extensively studied in the progression of various types of cancer, while the mechanism of circKIAA1797 is rarely studied in gastric cancer (GC). Hence, this research aimed to investigate the expression of exosomal circKIAA1797 and its biological function in GC cells. Exosomes were extracted from the serum of GC patients and identified by transmission electron microscopy (TEM) and nanoparticle tracking analyzer (NTA). CD81, CD63, Bcl-2, Bax, and pre-leukemia transcription factor 3 (PBX3) protein levels were detected using western blot assay. circKIAA1797, microRNA-4429 (miR-4429), and PBX3 mRNA were determined by quantitative real-time PCR (RT-qPCR). Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and flow cytometry assay. Glucose consumption and lactate production levels were examined using glycolysis detection kits. The interaction between miR-4429 and circKIAA1797 or PBX3 was identified using dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. Xenograft mouse model assay was used to investigate the effect of exosomal circKIAA1797 in vivo. It was found that circKIAA1797 was up-regulated in GC tissues and cells, as well as in the exosomes derived from the serum of GC patients. Silencing of exosomal circKIAA1797 could hamper cell progression and glycolytic metabolism of GC. Mechanically, circKIAA1797 acted as a sponge of miR-4429 to regulate PBX3 expression. Moreover, the knockdown of exosomal circKIAA1797 repressed tumor growth in vivo. Our data demonstrated that knockdown of exosomal circKIAA1797 suppressed GC malignant phenotypes by regulating miR-4429/PBX3 axis, which might offer a promising therapeutic strategy for GC treatment.

Advances and challenges in biocathode microbial electrolysis cells for chlorinated organic compounds degradation from electroactive perspectives.

Microbial electrolysis cell (MEC) is a promising in-situ strategy for chlorinated organic compound (COC) pollution remediation due to its high efficiency, low energy input, and long-term potential. Reductive dechlorination as the most critical step in COC degradation which takes place primarily in the cathode chamber of MECs is a complex biochemical process driven by the behavior of electrons. However, no information is currently available on the internal mechanism of MEC in dechlorination from the perspective of the whole electron transfer procedure and its dependent electrode materials. This review addresses the underlying mechanism of MEC on the fundamental of the generation (electron donor), transmission (transfer pathway), utilization (functional microbiota) and reception (electron acceptor) of electrons in dechlorination. In addition, the vital role of varied cathode materials involved in the entire electron transfer procedure during COC dechlorination is emphasized. Subsequently, suggestions for future research, including model construction, cathode material modification, and expanding the applicability of MECs to removal gaseous COCs have been proposed. This paper enriches the mechanism of COC degradation by MEC, and thus provides the theoretical support for the scale-up bioreactors for efficient COC removal.

Regression modelling of conditional morphogene expression links and quantifies the impact of growth rate, fitness and macromorphology with protein secretion in Aspergillus niger.

BACKGROUND: Filamentous fungi are used as industrial cell factories to produce a diverse portfolio of proteins, organic acids, and secondary metabolites in submerged fermentation. Generating optimized strains for maximum product titres relies on a complex interplay of molecular, cellular, morphological, and macromorphological factors that are not yet fully understood. RESULTS: In this study, we generate six conditional expression mutants in the protein producing ascomycete Aspergillus niger and use them as tools to reverse engineer factors which impact total secreted protein during submerged growth. By harnessing gene coexpression network data, we bioinformatically predicted six morphology and productivity associated 'morphogenes', and placed them under control of a conditional Tet-on gene switch using CRISPR-Cas genome editing. Strains were phenotypically screened on solid and liquid media following titration of morphogene expression, generating quantitative measurements of growth rate, filamentous morphology, response to various abiotic perturbations, Euclidean parameters of submerged macromorphologies, and total secreted protein. These data were built into a multiple linear regression model, which identified radial growth rate and fitness under heat stress as positively correlated with protein titres. In contrast, diameter of submerged pellets and cell wall integrity were negatively associated with productivity. Remarkably, our model predicts over 60% of variation in A. niger secreted protein titres is dependent on these four variables, suggesting that they play crucial roles in productivity and are high priority processes to be targeted in future engineering programs. Additionally, this study suggests A. niger dlpA and crzA genes are promising new leads for enhancing protein titres during fermentation. CONCLUSIONS: Taken together this study has identified several potential genetic leads for maximizing protein titres, delivered a suite of chassis strains with user controllable macromorphologies during pilot fermentation studies, and has quantified four crucial factors which impact secreted protein titres in A. niger.

Swertia cincta Burkill alleviates LPS/D-GalN-induced acute liver failure by modulating apoptosis and oxidative stress signaling pathways.

Swertia cincta Burkill is widely distributed along the southwestern region of China. It is known as "Dida" in Tibetan and "Qingyedan" in Chinese medicine. It was used in folk medicine to treat hepatitis and other liver diseases. To understand how Swertia cincta Burkill extract (ESC) protects against acute liver failure (ALF), firstly, the active ingredients of ESC were identified using liquid chromatography-mass spectrometry (LC-MS), and further screening. Next, network pharmacology analyses were performed to identify the core targets of ESC against ALF and further determine the potential mechanisms. Finally, in vivo experiments as well as in vitro experiments were conducted for further validation. The results revealed that 72 potential targets of ESC were identified using target prediction. The core targets were ALB, ERBB2, AKT1, MMP9, EGFR, PTPRC, MTOR, ESR1, VEGFA, and HIF1A. Next, KEGG pathway analysis showed that EGFR and PI3K-AKT signaling pathways could have been involved in ESC against ALF. ESC exhibits hepatic protective functions via anti-inflammatory, antioxidant, and anti-apoptotic effects. Therefore, the EGFR-ERK, PI3K-AKT, and NRF2/HO-1 signaling pathways could participate in the therapeutic effects of ESC on ALF.

Impact of carbon monoxide on performance and microbial community of extreme-thermophilic hydrogenotrophic methanation in horizontal rotary bioreactor.

A novel horizontal rotary bioreactor was developed for upgrading biogas from coke oven gas at extreme-thermophilic condition. The introduction of CO decreased the outlet methane content from 80% to 50% due to insufficient H2. This hindrance was overcome by increasing the proportion of incoming hydrogen, coupled with a prolonged gas retention time from 24 to 72 h, leading to a restoration of methane content to 91.6%. Notably, CO and CO2 exhibited a competitive relationship to hydrogen, which was determined by their contents. The substitution of Methanothermobacter for Methanobacterium as the dominant genus was observed at 70 °C, with relative abundance exceeding 98%. Incorporation of CO increased bacteria diversity and fostered a syntrophic relationship between the bacterial community and M. thermautotrophicus. This study provides both theoretical basis and practical support for biogas upgrading from coke oven gas using a biofilm reactor, thus aiding its future industrialization prospects.

Internal driving mechanism of microbial community and metabolic pathway for psychrophilic anaerobic digestion by microbial electrolysis cell.

The system that microbial electrolysis cell coupled anaerobic digestion (termed MEC-AD) with metal organic framework-modified cathode was operated under different voltage levels (0-1.2 V) at 20 °C. The maximum methane yield increased to 0.23 ± 0.01 LCH4 g-1COD at 0.9 V, with 28% improvement compared to 0 V (0.18 ± 0.01 LCH4 g-1COD). Moreover, total volatile fatty acid and propionate accumulation decreased by 32% and 15% at 0.9 V, indicating the system has potential to alleviate acidity suppression. Acidogens and electroactive microorganisms was clearly enriched with increasing applied voltage. Specifically, the abundance of Smithella increased, which could degrade propionate to acetate. Methanosaeta was dominant, accounting for ca. 40.1%∼55.1% of the archaea community at 0.3-1.2 V. Furthermore, the system reinforced psychrophilic methanogenesis by activating important enzymes involved in related metabolism pathways. Overall, this study provides perspective on the future practical application for the regulation of psychrophilic AD in electrochemically integrated bioreactors.

Advancement in understanding the role of ferroptosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic disease of unknown etiology. The primary manifestation of RA is inflammatory synovitis, which eventually leads to deformity and functional loss. Ferroptosis is a non-apoptosis form of cell death that depends on intracellular iron accumulation. This leads to an increase in reactive oxygen species (ROS) induced-lipid peroxidation. The underlying mechanisms of ferroptosis are System Xc- and Glutathione metabolism, regulation of glutathione peroxidase 4 activity, and ROS generation. Recent studies have shown an association between the pathogenesis of RA and ferroptosis, suggesting the involvement of ferroptosis in the onset and progression of RA. In this review, we have focused on the mechanism of ferroptosis and its association with RA pathogenesis. Further, we discuss the status of therapeutics targeting ferroptosis in the treatment of patients with RA. Targeting ferroptosis could be a potential therapeutic approach for RA treatment.

Do neutrophil to lymphocyte ratio and platelet to lymphocyte ratio associate with frailty in elderly inpatient with comorbidity?

OBJECTIVE: Inflammation is one of the pathogenesis of frailty, Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are newly proposed inflammatory indicators. This study aimed to explore the relationship between NLR, PLR and frailty in elderly inpatient with comorbidity. METHODS: Inpatient elderly with comorbidity in our geriatric department from January 2015 to December 2018 were selected, and three groups, which included frailty, pre-frailty and robust, were divided by 5-item FRAIL scale. General data of the patients were collected, and comprehensive geriatric assessment was performed. NLR and PLR were calculated by neutrophil, lymphocyte and platelet in blood. SPSS24.0 software was used for analysis. RESULTS: CONCLUSION: Although results from the present study revealed associations between frailty and neutrophil and NLR in elderly inpatient with comorbidity, the potential role of these inflammation indicators on frailty needs further prospective investigation and researches involving larger population to improve its reliability.

The Short Health Scale: A Valid and Reliable Quality-of-Life Scale for Mainland Chinese Patients with Inflammatory Bowel Disease.

Background: The aim of our study was to translate and validate the mainland Chinese version of the short health scale (SHS), a disease-specific quality-of-life (QoL) scale for patients with inflammatory bowel disease (IBD). Methods: The SHS was translated and validated according to the standard process: a translation and back-translation procedure and a reliability and validation study. Patients with IBD were enrolled, and their QoL was assessed using the SHS, the short inflammatory bowel disease questionnaire (SIBDQ), and the Bristol stool form scale. Reliability (internal consistency reliability, split-half reliability, and test-retest reliability) and validity analyses were performed to evaluate the psychometric characteristics of the SHS. The impacts of different severity of major symptoms on QoL were analyzed by comparing the scores of SHS. Results: A total of 112 patients with IBD (69 with ulcerative colitis and 43 with Crohn's disease) completed the mainland Chinese version of the SHS, and 34 patients completed the SHS a second time within one to two weeks. Cronbach's alpha value of the SHS was 0.90, and its split-half coefficient was 0.83. Intraclass correlation coefficients of the four items ranged from 0.52 to 0.72. All four items of the SHS were significantly associated with the corresponding domains of the SIBDQ, with correlation coefficients ranging from -0.52 to -0.69 (p < 0.001). The results of confirmatory factor analysis indicated a good fit of the one-factor model, with comparative fit index (CFI) = 0.878, normed fit index (NFI) = 0.874, incremental fit index (IFI) = 0.880, and goodness of fit index (GFI) = 0.842. The patients with severe symptoms had higher scores in the SHS than those with no or mild symptoms. Conclusions: The SHS was simple and quick to be used. The SHS had good validity and reliability and was suitable for evaluating the QoL of patients with IBD in mainland China.

A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical drugs based on the inhibition of AD pathological features is imperative. METHODS: First, we utilized the HERB database and Swisstarget Prediction database to get the related targets of curcumin and intersected with the AD targets. The intersection targets were used to construct the protein-protein interaction network and performed gene ontology and kyoto encyclopedia of genes and genomes analyses. Further, we obtained targets of curcumin against AD-related tau and aß pathology via the AlzData database. These targets were applied to perform GEO and receiver operating characteristic analyses. Finally, the reliability of the core targets was evaluated using molecular docking technology. RESULTS: We identified 49 targets of curcumin against AD, and kyoto encyclopedia of genes and genomes pathway enrichment analysis demonstrated that the Alzheimer disease pathway (has05010) was significantly enriched. Even more, we obtained 16 targets of curcumin-related Aß and tau pathology. Among these targets, 8 targets involved the Alzheimer disease pathway and the biological process analyses showed that positive regulation of cytokine production (GO:0001819) was significantly enriched. Bioinformatic analyses indicated that HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression was significantly different compared to the control group in the AD patients. Finally, molecular docking studies suggested these genes have a good binding force with curcumin. CONCLUSIONS: In this study, we identified curcumin exerted the effect of treating AD by regulating multitargets and multichannels through the method of network pharmacology.

Evaluation of Aspergillus niger Six Constitutive Strong Promoters by Fluorescent-Auxotrophic Selection Coupled with Flow Cytometry: A Case for Citric Acid Production.

Aspergillus niger is an important industrial workhorse for the biomanufacturing of organic acids, proteins, etc. Well-controlled genetic regulatory elements, including promoters, are vital for strain engineering, but available strong promoters for A. niger are limited. Herein, to efficiently assess promoters, we developed an accurate and intuitive fluorescent-auxotrophic selection workflow based on mCherry, pyrG, CRISPR/Cas9 system, and flow cytometry. With this workflow, we characterized six endogenous constitutive promoters in A. niger. The endogenous glyceraldehyde-3-phosphate dehydrogenase promoter PgpdAg showed a 2.28-fold increase in promoter activity compared with the most frequently used strong promoter PgpdAd from A. nidulans. Six predicted conserved motifs, including the gpdA-box, were verified to be essential for the PgpdAg activity. To demonstrate its application, the promoter PgpdAg was used for enhancing the expression of citrate exporter cexA in a citric acid-producing isolate D353.8. Compared with the cexA controlled by PgpdAd, the transcription level of the cexA gene driven by PgpdAg increased by 2.19-fold, which is consistent with the promoter activity assessment. Moreover, following cexA overexpression, several genes involved in carbohydrate transport and metabolism were synergically upregulated, resulting in up to a 2.48-fold increase in citric acid titer compared with that of the parent strain. This study provides an intuitive workflow to speed up the quantitative evaluation of A. niger promoters and strong constitutive promoters for fungal cell factory construction and strain engineering.

Decreased salivary α-amylase activity responding to citric acid stimulation in Myasthenia gravis with malnutrition.

OBJECTIVES: Malnutrition, defined according to Nutritional risk screening (NRS 2002), is commonly observed in patients of Myasthenia gravis (MG), a neuromuscular disorder manifested by varied degrees of skeletal muscle weakness. Because biochemical composition of saliva changes in correspondence to alterations in nutritional status, we tested our hypothesis that a certain saliva component(s) might serve as a biomarker(s) for nutrition status of MG, particularly for those MG patients with high risk of malnutrition. MATERIALS AND METHODS: 60 MG patients and 60 subjects belonging to the healthy control group (HCG) were enrolled in this case-control study. The salivary α-amylase (sAA) activity, salivary flow rate (SFR), pH, total protein density (TPD), and the concentrations of chloride and calcium ions in MG group with or without malnutrition were measured before and after citric acid stimulation. Thereafter, the relationship between sAA activity and BMI was determined in MG and HCG. RESULTS: Compared with HCG, more patients with malnutrition, increased TPD and chloride and calcium concentrations but decreased pH value and SFR both before and after acid stimulation, as well as reduced sAA activity, pH and TPD responses to acid stimulation. MG with malnutrition showed decreased sAA activity and TPD responding to acid stimulation compared with those without malnutrition. Compared with normal BMI, sAA activity response to acid stimulation was reduced in low BMI. There was a significant strong positive correlation between the ratio of sAA activity and BMI in MG. CONCLUSIONS: Salivary biochemical characteristics are abnormally altered in MG with malnutrition. Altered sAA activity responding to acid stimulation was associated with malnutrition. CLINICAL RELEVANCE: Decreased sAA activity responding to acid stimulation can reflect malnutrition state and may be one potential screening marker for MG patients with high risk of malnutrition.

Diurnal pattern of salivary alpha-amylase and cortisol under citric acid stimulation in young adults.

Background: Saliva composition has diurnal variations. Citric acid stimulation plays a major role in the change of salivary flow rate and salivary composition. However, diurnal variations and sex differences in salivary alpha-amylase (sAA), pH, salivary flow rate (SFR), and salivary cortisol before and after citric acid stimulation remain unclear. Methods: We recruited 30 healthy volunteers, including 15 women (24.7 ± 1.0 years old) and 15 men (25.3 ± 1.3 years old). At four time points (T1, 7:00; T2, 10:00; T3, 16:00; and T4, 20:00), saliva was collected from healthy volunteers before and after citric acid stimulation; and sAA, pH, SFR and salivary cortisol were measured and compared between men and women. Results: There were circadian fluctuations in sAA activity, SFR, pH, and cortisol level both before and after citric acid stimulation, and the diurnal fluctuations of these indexes were not affected by citric acid stimulation. There were significant differences in salivary cortisol between men and women before and after acid stimulation in T1. Neither SFR nor pH showed sex-related differences before or after acid stimulation. The variation trend of sAA activity was contrary to that of cortisol, with a significant negative correlation. Conclusions: Our data suggest that sAA and cortisol showed diurnal fluctuation, and the variation characteristics of male and female under resting state and acid stimulation were basically the same. The variation trend of salivary alpha-amylase activity was opposite to that of cortisol, with significant negative correlation. Our findings may enable the selection of the correct sampling time for research and the selection of appropriate sampling strategies in studies investigating chronic psychosocial conditions.