Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction.

In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients.

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.

Novel insights into autophagy in gastrointestinal pathologies, mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure.

In this editorial, we comment on three articles published in a recent issue of World Journal of Gastroenterology. There is a pressing need for new research on autophagy's role in gastrointestinal (GI) disorders, and also novel insights into some liver conditions, such as metabolic dysfunction-associated fatty liver disease (MAFLD) and acute liver failure (ALF). Despite advancements, understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete. Moreover, MAFLD's pathogenesis, encompassing hepatic steatosis and metabolic dysregulation, require further elucidation. Similarly, the mechanisms underlying ALF, a severe hepatic dysfunction, are poorly understood. Innovative studies exploring the interplay between autophagy and GI disorders, as well as defined mechanisms of MAFLD and ALF, are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease: Clinical implications.

In this editorial, we comment on the article by Chen et al recently published in 2024. We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase (ALT) would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease (MAFLD). This is important given the increasing prevalence of MAFLD and obesity globally. Currently, a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT. The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered, particularly as their study found that 83.12% of their study population with a diagnosis of MAFLD had a normal ALT. The main advantages of screening would be to identify patients and provide intervention early, the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis. However, there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered. Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity, although studies have not yet shown a significant improvement in fibrosis regression. It would also require a huge amount of resource if a reduced ALT level alone was used as criteria; it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk. Currently, there is not a good argument to recommend widespread screening with a reduced ALT level as this is unlikely to be cost-effective. This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories. Although studies previously have suggested a more pragmatic approach in screening those over the age of 60, this is likely to change with the increasing incidence of obesity within the younger age groups. The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Evaluation of elevated serum liver enzymes and metabolic syndrome in the PERSIAN Guilan cohort study population.

Objective: The purpose of this study is to evaluate the association between elevated serum liver enzymes and Metabolic Syndrome (MetS) in Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study (PGCS) population. Methods: This cross-sectional study involved 10,519 individuals between the ages of 35 and 70 enrolled in the PGCS. The gathered data encompassed demographic information, anthropometric measurements, blood pressure, and biochemical indicators. MetS was defined by the National Cholesterol Education Program-Adult Treatment Panel III criteria (NCEP-ATP III). The associations between elevated liver enzymes and MetS were examined using logistic regression analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated. Results: The prevalence of MetS was 41.8 %, and the prevalence of elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were 19.4, 4.6, 11.6, and 5.1 %, respectively. In the unadjusted model, elevated ALT, AST, and GGT were associated with increased odds of MetS (OR = 1.55, 95 % CI: 1.41-1.71; OR = 1.29, 95 % CI: 1.07-1.55, and OR = 1.90, 95 % CI: 1.69-2.14, respectively). These associations remained significant for ALT and GGT after adjustment for some demographic and clinical characteristics (aOR = 1.31, 95 % CI: 1.17-1.46 and aOR = 1.30, 95 % CI: 1.14-1.49, respectively). In addition, the odds of MetS increased with the number of elevated liver enzymes, up to almost 1.32-fold among subjects with three/four elevated liver enzymes. Conclusion: The higher incidence of elevated liver enzymes was associated with an increased likelihood of MetS. Including liver markers in diagnosing and predicting MetS holds promise and is considered a possible approach.

Branched-chain amino acids and L-alanine supplementation ameliorate calcium dyshomeostasis in sarcopenia: New insights for nutritional interventions.

Introduction: During aging, sarcopenia and decline in physiological processes lead to partial loss of muscle strength, atrophy, and increased fatigability. Muscle changes may be related to a reduced intake of essential amino acids playing a role in proteostasis. We have recently shown that branched-chain amino acid (BCAA) supplements improve atrophy and weakness in models of muscle disuse and aging. Considering the key roles that the alteration of Ca2+-related homeostasis and store-operated calcium entry (SOCE) play in several muscle dysfunctions, this study has been aimed at gaining insight into the potential ability of BCAA-based dietary formulations in aged mice on various players of Ca2+ dyshomeostasis. Methods: Seventeen-month-old male C57BL/6J mice received a 12-week supplementation with BCAAs alone or boosted with two equivalents of L-alanine (2-Ala) or with dipeptide L-alanyl-L-alanine (Di-Ala) in drinking water. Outcomes were evaluated on ex vivo skeletal muscles indices vs. adult 3-month-old male C57BL/6J mice. Results: Ca2+ imaging confirmed a decrease in SOCE and an increase of resting Ca2+ concentration in aged vs. adult mice without alteration in the canonical components of SOCE. Aged muscles vs. adult muscles were characterized by a decrease in the expression of ryanodine receptor 1 (RyR1), the Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) pump, and sarcalumenin together with an alteration of the expression of mitsugumin 29 and mitsugumin 53, two recently recognized players in the SOCE mechanism. BCAAs, particularly the formulation BCAAs+2-Ala, were able to ameliorate all these alterations. Discussion: These results provide evidence that Ca2+ homeostasis dysfunction plays a role in the functional deficit observed in aged muscle and supports the interest of dietary BCAA supplementation in counteracting sarcopenia-related SOCE dysregulation.

The ratio of alanine aminotransferase to high-density lipoprotein cholesterol is positively correlated with the insulin resistance in American adults: a population-based cohort study.

Introduction: Previous studies have demonstrated a correlation between the ratio of alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) in the serum and the risk of diabetes. However, no existing study has investigated the association between insulin resistance (IR) and ALT/HDL-C. Therefore, this study aims to explore the association between ALT/HDL-C and IR in American adults. Methods: A total of 7,599 adults selected from the National Health and Nutrition Examination Survey (NHANES) in 2013 to 2020 were studied. IR was assessed based on the homeostatic model assessment of insulin resistance (HOMA-IR). And the association between IR and ALT/HDL-C was assessed through multiple logistic regression, generalized smooth curve fitting and subgroup analyses. Results: Multiple logistic regression analysis indicated a significant correlation between IR and ALT/HDL-C, with odds ratios (OR) of 1.04 (95% CI = 1.02-1.05) in males and 1.04 (95% CI = 1.02-1.07) in females. A non-linear association and saturation effect between ALT/HDL-C and IR risk were identified, with an inverted L shaped curve and an inflection point at 33.62. The area under the ROC curve (AUC) of ALT/HDL-C was significantly larger (AUC = 0.725 for males and 0.696 for females, all p < 0.01) compared with the use of ALT, HDL-C, AST and AST/ALT. Subgroup analysis showed a significantly higher independent association in obese individuals and individuals aged ≥50 years (All P interaction <0.05). Conclusion: Elevated ALT/HDL-C demonstrates a significant correlation with IR, which can be used as a potential indicator of IR in American adults.

Seroepidemiology of hepatitis B virus (HBV) and relationship to serum transaminase levels in Indian population.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value <0.0001). The median viral load was significantly higher in HBeAg-positive cases (4.72 log10 copies/mL) than in HBeAg-negative individuals (4.23 log10 copies/mL; P = 0.997). Additionally, a higher proportion of HBeAg-positive samples (P = 0.0001) had HBV-DNA levels above 10,000 copies/mL.

Through virtual saturation mutagenesis and rational design for superior substrate conversion in engineered d-amino acid oxidase.

The d-amino acid oxidase (DAAO) is pivotal in obtaining optically pure l-glufosinate (l-PPT) by converting d-glufosinate (d-PPT) to its deamination product. We screened and designed a Rasamsonia emersonii DAAO (ReDAAO), making it more suitable for oxidizing d-PPT. Using Caver 3.0, we delineated three substrate binding pockets and, via alanine scanning, identified nearby key residues. Pinpointing key residues influencing activity, we applied virtual saturation mutagenesis (VSM), and experimentally validated mutants which reduced substrate binding energy. Analysis of positive mutants revealed elongated side-chain prevalence in substrate binding pocket periphery. Although computer-aided approaches can rapidly identify advantageous mutants and guide further design, the mutations obtained in the first round may not be suitable for combination with other advantageous mutations. Therefore, each round of combination requires reasonable iteration. Employing VSM-assisted screening multiple times and after four rounds of combining mutations, we ultimately obtained a mutant, N53V/F57Q/V94R/V242R, resulting in a mutant with a 5097% increase in enzyme activity compared to the wild type. It provides valuable insights into the structural determinants of enzyme activity and introduces a novel rational design procedure.

Effects of d-alanine Intake on Amino Acid Metabolism and Kidney Function in Healthy Adults: A Multicenter, Randomized Pilot Study.

Background: d-alanine administration prevented kidney damage in a murine acute kidney injury model. Further data are needed on the influence of d-alanine on kidney function in humans. Objective: This study investigated the effects of d-alanine intake on amino acid metabolism and kidney function in healthy volunteers. Methods: This multicenter pilot study randomly assigned individuals from the general Japanese population to receive 3 g or 6 g of d-alanine intake per day for 7 d in a 1:1 ratio. The primary endpoint was the mean change in plasma and urine d-alanine levels from baseline to 7 d after intake. The secondary endpoints were mean changes in kidney function and other clinical factors. Safety was assessed by evaluating adverse events and clinical parameters. Results: We randomly assigned 24 participants to the 3-g (n = 12) and 6-g d-alanine (n = 12) groups. The mean baseline estimated glomerular filtration rate (eGFR) was 73 mL/min/1.73 m2. The mean plasma d-alanine concentration increased from baseline by 77.5 ± 34.3 and 192.1 ± 80.9 nmol/mL in the 3-g and 6-g d-alanine groups (both p < 0.0001), respectively, in a dose-dependent manner (between-group difference: 114.6 nmol/mL; 95% CI: 62.1-167.2; P = 0.0002). A similar increase was observed for the urine d-alanine to creatinine ratio. The mean eGFR was elevated by 5.7 ± 8.8 mL/min/1.73 m2 in the 6-g d-alanine group (P = 0.045) but did not significantly change in the 3-g d-alanine group. Nonserious adverse events were reported in 11 participants. Conclusions: d-alanine intake increased plasma and urine d-alanine levels and was well tolerated in participants with normal kidney function. These results will be useful in future trials investigating the effects of d-alanine intake on kidney disease progression in patients with chronic kidney disease.This trial was registered at the UMIN Clinical Trials Registry as UMIN000051466.

A combined association of obesity, alanine aminotransferase and creatinine with hyperuricemia in youth aged 13-20 years.

Background: Despite extensive research on hyperuricemia (HUA) in adults, there remains a dearth of studies examining this condition in youth. Consequently, our objective was to investigate the prevalence of HUA among youth in the United States, as well as identify the corresponding risk factors. Methods: This study employed a nationally representative subsample of 1,051 youth aged 13-20 from the US National Health and Nutrition Examination Survey (NHANES) conducted between January 2017 and March 2020. Univariate and multivariate techniques were utilized to examine the association between HUA and obesity, dietary nutrients, liver and kidney function, glucose and lipid metabolism, inflammation, and other indicators in the adolescent population. Results: The study encompassed a cohort of 1,051 youth aged 13-20 years, comprising 538 boys and 513 girls. The overall prevalence of HUA was found to be 7% (74 out of 1,051). Univariate analysis revealed that the HUA group exhibited greater age, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Additionally, the prevalence of obesity was significantly higher in the HUA group compared to the non- HUA group (all p < 0.05). Regarding biochemical indicators, the levels of urea nitrogen, creatinine (Cr), alanine aminotransferase (ALT), glutamic oxalic aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), and HS C reactive protein (Hs CRP) were found to be significantly higher in the HUA group compared to the non-HUA group (all p < 0.05). Further analysis using binary logistics regression showed that BMI (p = 0.024, OR1.158, 95%CI1.019-1.316), ALT (p = 0.020, OR1.032, 95%CI1.005-1.059), and Cr (p = 0.016, OR1.028, 95%CI1.005-1.051) were identified as risk factors for HUA, after controlling for age, gender, BMI, WC, HC, WHR, ALT, AST, GGT, TG, TC, Cr, Hs CRP, and other indicators. Interestingly, neither univariate nor multivariate analysis found any association between dietary nutrients and the risk of HUA (all p > 0.05). Conclusion: High BMI remains a major risk factor for HUA in US youth aged 13-20 years, and ALT and Cr levels should be closely monitored along with serum uric acid.

Nano silicated-FeAl2O4 functionalized by DL-alaninium nitrate ionic liquid (FeAl2O4-SiO2@[DL-Ala][NO3]) as versatile promotor for aqua-mediated synthesis of spiro[chromenopyrazole-indene-triones and spiro[chromenopyrazole-indoline-diones.

In this work, the spinel FeAl2O4 was prepared and functionalized step-by-step with silica and alaninium nitrate ionic liquid ([DL-Ala][NO3]) to produce a bio-based multi-layered nanostructure (nano FeAl2O4-SiO2@[DL-Ala][NO3]). The obtained magnetized inorganic-bioorganic nanohybrid characterized by Fourier transform infrared spectroscopy (FT-IR), vibrating-sample magnetometry (VSM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), transmission electron microscopy (TEM), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), X-ray fluorescence (XRF), and X-Ray diffraction (XRD) analysis. A facile synthesis of some tricyclic dihydro-spiro[chromeno[2,3-c]pyrazole-4,2'-indene]triones and dihydro-spiro[chromeno[2,3-c]pyrazole-4,3'-indoline]diones via domino four-component one-pot reaction of various hydrazine derivatives, ethyl acetoacetate, heterocyclic 1,2-ketones (ninhydrin, isatin, 5-bromoisatin) and cyclic 1,3-diketones (dimedone and 1,3-cyclohexanedine), examined in the presence of nano FeAl2O4-SiO2@[DL-Ala][NO3] nanohybrid in refluxing aqueous media, successfully. The multi-aspect characteristics of the nanohybrid which consist of magnetized inorganic and bioorganic parts, could be the reason of its special catalytic efficacy. The recovery and reusability of the FeAl2O4-SiO2@[DL-Ala][NO3] magnetized nanoparticles (MNPs) were performed in two runs without significant activity loss.

Alanine and glutamate catabolism collaborate to ensure the success of Bacillus subtilis sporulation.

Sporulation as a typical bacterial differentiation process has been studied for decades. However, two crucial aspects of sporulation, (i) the energy sources supporting the process, and (ii) the maintenance of spore dormancy throughout sporulation, are scarcely explored. Here, we reported the crucial role of RocG-mediated glutamate catabolism in regulating mother cell lysis, a critical step for sporulation completion of Bacillus subtilis, likely by providing energy metabolite ATP. Notably, rocG overexpression resulted in an excessive ATP accumulation in sporulating cells, leading to adverse effects on future spore properties, e.g. increased germination efficiency, reduced DPA content, and lowered heat resistance. Additionally, we revealed that Ald-mediated alanine metabolism was highly related to the inhibition of premature germination and the maintenance of spore dormancy during sporulation, which might be achieved by decreasing the typical germinant L-alanine concentration in sporulating environment. Our data inferred that sporulation of B. subtilis was a highly orchestrated biological process requiring a delicate balance in diverse metabolic pathways, hence ensuring both the completion of sporulation and production of high-quality spores.

The role of neutrophil extracellular traps in ß-methylamino L-alanine-induced liver injury in mice.

The non-protein amino acid ß-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a 'double-edged sword' for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Non-clinical Safety Evaluation of Camelina Oil: Acute and 12-Week Oral Toxicities.

This study assessed the acute and sub-chronic toxicity of Camelina oil, a well-known oil rich in polyunsaturated fatty acids that enhance cellular immunity and human health, in Wistar rats. Wistar rats, 5 per sex per group, were randomly assigned to three groups for acute (14 days) toxicity studies and five groups for sub-chronic (90 days) toxicity studies. In the acute study, Camelina sativa oil was administered orally at a single dose of 5000 mg/kg of body weight (BW). The positive control group received a single dose of 5 000 mg/kg BW Canola oil by gavage. In the sub-chronic study, Groups III-V received 250, 500, and 1 000 mg/kg BW of Camelina oil, while Groups I and II received ultra-pure water and Canola oil at a dose of 500 mg/kg BW, respectively. Throughout the experiment, clinical signs, mortality, and body weight were monitored. At the end of the sub-chronic study, hematological, biochemical, and histopathological investigations were conducted. Administration of Camelina oil and Canola had no significant effect on daily weight gain (P > 0.05) of the test rats. Serum calcium levels decreased while phosphorous levels increased in male rats treated with Camelina oil. Other hematological and biochemical parameters showed no significant differences or dose-response effects between control and seed oil groups in both sexes (P < 0.05). Moreover, in animal necropsy, there were no apparent lesions in the liver, heart, and kidney organs in any of the doses administered. In conclusion, the results suggest that oral administration of Camelina oil is unlikely to be toxic. Therefore, the possibility for the development of future human nutrition should be considered.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic liver disease (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Metabolic Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and age independently predict ALT levels among blood donors. Over the last few decades, the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges. With this backset, Chen et al have recently published a study which has two main findings. First, > 80% of individuals with MAFLD had normal ALT levels. Second, there was a linear increasing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD. This study has biologically credible findings. However, it inaccurately considered sex differences in the MAFLD arena. Therefore, future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Fine and combinatorial regulation of key metabolic pathway for enhanced ß-alanine biosynthesis with non-inducible Escherichia coli.

ß-Alanine is the only ß-amino acid in nature and one of the most important three-carbon chemicals. This work was aimed to construct a non-inducible ß-alanine producer with enhanced metabolic flux towards ß-alanine biosynthesis in Escherichia coli. First of all, the assembled E. coli endogenous promoters and 5'-untranslated regions (PUTR) were screened to finely regulate the combinatorial expression of genes panDBS and aspBCG for an optimal flux match between two key pathways. Subsequently, additional copies of key genes (panDBS K104S and ppc) were chromosomally introduced into the host A1. On these bases, dynamical regulation of the gene thrA was performed to reduce the carbon flux directed in the competitive pathway. Finally, the ß-alanine titer reached 10.25 g/L by strain A14-R15, 361.7% higher than that of the original strain. Under fed-batch fermentation in a 5-L fermentor, a titer of 57.13 g/L ß-alanine was achieved at 80 h. This is the highest titer of ß-alanine production ever reported using non-inducible engineered E. coli. This metabolic modification strategy for optimal carbon flux distribution developed in this work could also be used for the production of various metabolic products.

Amino acids regulating skeletal muscle metabolism: mechanisms of action, physical training dosage recommendations and adverse effects.

Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and ß-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research.

ß-N-methylamino-L-alanine production, photosynthesis and transcriptional expression in a possible mutation strain and a wild strain of Thalassiosira minima.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) produced by marine diatoms has been implicated as an important environmental trigger of neurodegenerative diseases in humans. However, the biosynthesis mechanism of BMAA in marine diatoms is still unknown. In the present study, the strain of diatom Thalassiosira minima almost lost the biosynthesis ability for BMAA after a long-term subculture in our laboratory. The production of BMAA-containing proteins in the mutant strain of T. minima reduced to 18.2 % of that in the wild strain, meanwhile the cell size decreased but pigment content increased in the mutant strain. Take consideration of our previous transcriptional data on the mixed diatom and cyanobacterium cultures, the current transcriptome analysis showed four identical and highly correlated KEGG pathways associated with the accumulation of misfolded proteins in diatom, including ribosome, proteasome, SNARE interactions in vesicle transport, and protein processing in the endoplasmic reticulum. Analysis of amino acids and transcriptional information suggested that amino acid synthesis and degradation are associated with the biosynthesis of BMAA-containing proteins. In addition, a reduction in the precision of ubiquitination-mediated protein hydrolysis and vesicular transport by the COPII system will exacerbate the accumulation of BMAA-containing proteins in diatoms.