The intestinal epithelial-macrophage-crypt stem cell axis plays a crucial role in regulating and maintaining intestinal homeostasis.

The intestinal tract plays a vital role in both digestion and immunity, making its equilibrium crucial for overall health. This equilibrium relies on the dynamic interplay among intestinal epithelial cells, macrophages, and crypt stem cells. Intestinal epithelial cells play a pivotal role in protecting and regulating the gut. They form vital barriers, modulate immune responses, and engage in pathogen defense and cytokine secretion. Moreover, they supervise the regulation of intestinal stem cells. Macrophages, serving as immune cells, actively influence the immune response through the phagocytosis of pathogens and the release of cytokines. They also contribute to regulating intestinal stem cells. Stem cells, known for their self-renewal and differentiation abilities, play a vital role in repairing damaged intestinal epithelium and maintaining homeostasis. Although research has primarily concentrated on the connections between epithelial and stem cells, interactions with macrophages have been less explored. This review aims to fill this gap by exploring the roles of the intestinal epithelial-macrophage-crypt stem cell axis in maintaining intestinal balance. It seeks to unravel the intricate dynamics and regulatory mechanisms among these essential players. A comprehensive understanding of these cell types' functions and interactions promises insights into intestinal homeostasis regulation. Moreover, it holds potential for innovative approaches to manage conditions like radiation-induced intestinal injury, inflammatory bowel disease, and related diseases.

Domain Growth in Polycrystalline Graphene.

Graphene is a two-dimensional carbon allotrope which exhibits exceptional properties, making it highly suitable for a wide range of applications. Practical graphene fabrication often yields a polycrystalline structure with many inherent defects, which significantly influence its performance. In this study, we utilize a Monte Carlo approach based on the optimized Wooten, Winer and Weaire (WWW) algorithm to simulate the crystalline domain coarsening process of polycrystalline graphene. Our sample configurations show excellent agreement with experimental data. We conduct statistical analyses of the bond and angle distribution, temporal evolution of the defect distribution, and spatial correlation of the lattice orientation that follows a stretched exponential distribution. Furthermore, we thoroughly investigate the diffusion behavior of defects and find that the changes in domain size follow a power-law distribution. We briefly discuss the possible connections of these results to (and differences from) domain growth processes in other statistical models, such as the Ising dynamics. We also examine the impact of buckling of polycrystalline graphene on the crystallization rate under substrate effects. Our findings may offer valuable guidance and insights for both theoretical investigations and experimental advancements.

Critical dynamical behavior of the Ising model.

We investigate the dynamical critical behavior of the two- and three-dimensional Ising models with Glauber dynamics in equilibrium. In contrast to the usual standing, we focus on the mean-squared deviation of the magnetization M, MSD_{M}, as a function of time, as well as on the autocorrelation function of M. These two functions are distinct but closely related. We find that MSD_{M} features a first crossover at time τ_{1}∼L^{z_{1}}, from ordinary diffusion with MSD_{M}∼t, to anomalous diffusion with MSD_{M}∼t^{α}. Purely on numerical grounds, we obtain the values z_{1}=0.45(5) and α=0.752(5) for the two-dimensional Ising ferromagnet. Related to this, the magnetization autocorrelation function crosses over from an exponential decay to a stretched-exponential decay. At later times, we find a second crossover at time τ_{2}∼L^{z_{2}}. Here, MSD_{M} saturates to its late-time value ∼L^{2+γ/ν}, while the autocorrelation function crosses over from stretched-exponential decay to simple exponential one. We also confirm numerically the value z_{2}=2.1665(12), earlier reported as the single dynamic exponent. Continuity of MSD_{M} requires that α(z_{2}-z_{1})=γ/ν-z_{1}. We speculate that z_{1}=1/2 and α=3/4, values that indeed lead to the expected z_{2}=13/6 result. A complementary analysis for the three-dimensional Ising model provides the estimates z_{1}=1.35(2), α=0.90(2), and z_{2}=2.032(3). While z_{2} has attracted significant attention in the literature, we argue that for all practical purposes z_{1} is more important, as it determines the number of statistically independent measurements during a long simulation.

Antioxidant activity of the thioredoxin system.

The thioredoxin system is composed of thioredoxin (Trx), thioredoxin reductase (TR) and reduced nicotinamide adenine dinucleotide phosphate. Trx is an important antioxidant molecule that can resist cell death caused by various stresses and plays a prominent role in redox reactions. TR is a protein that contains selenium (selenocysteine), in three main forms, namely, TR1, TR2 and TR3. TR1, TR2 and TR3 are mainly distributed in the cytoplasm, mitochondria, and testes, respectively. TR can regulate cell growth and apoptosis. After a cell becomes cancerous, the expression of TR is increased to promote cell growth and metastasis. The Trx system is closely related to neurodegenerative diseases, parasitic infections, acquired immunodeficiency syndrome, rheumatoid arthritis, hypertension, myocarditis, and so on. In addition, the Trx system can remove the reactive oxygen species in the body and keep the inside and outside of the cell in a balanced state. In summary, the Trx system is an important target for the drug treatment of many diseases.

Transcriptomic analysis: the protection of over-expression thioredoxin reductase 1 in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathologic characteristic feature is the loss of dopaminergic neurons in the substantia nigra (SN). However, the biochemical mechanisms are unclear. A large number of studies have shown that oxidative damage is the primary cause of PD. Hence, antioxidants could become a suitable option to treat PD. The thioredoxin (Trx) system represents a useful, potentially disease-relevant oxidation-reduction system. Thioredoxin reductase 1 (TR1) is a significant component of the Trx system. METHODS: The overexpression lentivirus (LV) or LV-TR1 in the TR1-A53T model of PD by the stereotactic brain, and successful overexpression of LV or LV-TR1 in the MPP+-induced cellular model by LV or LV-TR1 transfection. RESULTS: We confirmed that interleukin-7 mRNA levels increased in MPP+ compared to that in the control and MPP+-TR1 groups using quantitative polymerase chain reaction. The γ-H2AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western blotting. The expression of Na+-K+-ATP was decreased in the MPP+ group compared to that in the control and MPP+-TR1 groups by high content screening. Tg-A53T(the C57BL/6 mice transferred with mutant human a-syn); TR1-A53T(A53T mice which were injected TR1-LV 2 µl in SNc on two sides with minipump).The mice were fed for 10 months. control (the N2a cells cultivated with DMEM); MPP+(the N2a cells dealt with MPP+(1 mM) 48 h), MPP+-LV (the N2a cells over-expressed LV for 24 h then dealt with MPP+(1 mM) 48 h). MPP+-TR1(the N2a cell over-expressed TR1-LV for 24 h then dealt with MPP+(1 mM) 48 h). From the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we confirmed that the overexpression of TR1 in SN pars compacta cells decreased oxidative stress, apoptosis, DNA damage, and inflammatory response and increased NADPH, Na+-K+-ATP, and immune response in this PD model. CONCLUSIONS: Our study shows that overexpressed TR1 can be developed as a neuroprotective agent for PD. Therefore, our findings demonstrate a new targeted protein for the treatment of PD.

Resequencing of a Pekin duck breeding population provides insights into the genomic response to short-term artificial selection.

BACKGROUND: Short-term, intense artificial selection drives fast phenotypic changes in domestic animals and leaves imprints on their genomes. However, the genetic basis of this selection response is poorly understood. To better address this, we employed the Pekin duck Z2 pure line, in which the breast muscle weight was increased nearly 3-fold after 10 generations of breeding. We denovo assembled a high-quality reference genome of a female Pekin duck of this line (GCA_003850225.1) and identified 8.60 million genetic variants in 119 individuals among 10 generations of the breeding population. RESULTS: We identified 53 selected regions between the first and tenth generations, and 93.8% of the identified variations were enriched in regulatory and noncoding regions. Integrating the selection signatures and genome-wide association approach, we found that 2 regions covering 0.36 Mb containing UTP25 and FBRSL1 were most likely to contribute to breast muscle weight improvement. The major allele frequencies of these 2 loci increased gradually with each generation following the same trend. Additionally, we found that a copy number variation region containing the entire EXOC4 gene could explain 1.9% of the variance in breast muscle weight, indicating that the nervous system may play a role in economic trait improvement. CONCLUSIONS: Our study not only provides insights into genomic dynamics under intense artificial selection but also provides resources for genomics-enabled improvements in duck breeding.

[Identification, biological characteristics, and screening of effective fungicides of Phoma rhei causing leaf spot on Polygonum cuspidatum].

Severe leaf spot on Polygonum cuspidatum was found in the planting base of P. cuspidatum in Fangxian county, Shiyan of Hubei province. To clarify the types of pathogens and their pathogenesis, the present study isolated and purified the pathogen of leaf spot disease of P. cuspidatum according to Koch's postulates, determined the pathogenicity of the pathogen, and investigated its biological characteristics. Meanwhile, the inhibitory effects of 11 types of fungicides on the bacteria were determined according to the mycelium growth rate, and suitable prevention and control drugs were selected. The results showed that the pathogen isolated from the diseased leaves of P. cuspidatum was Phoma rhei by morphological and molecular identification. The colony morphology and microscopic characteristics were the same as those of Ph. rhei. The homology of rDNA-ITS and TEF gene sequences with Ph. rhei reached 99.96% and 99.43%, respectively. The optimal growth temperature of Ph. rhei was 25 ℃, and the optimal pH was 7-10. Furthermore, Ph. rhei grew faster under dark or light conditions. In fungicides, 0.3% eugenol, 250 g·L~(-1) propiconazole, and 33.5% quinoline copper had significant inhibitory effects on the pathogen with EC_(50) values of 57.54, 59.58, 88.69 µg·mL~(-1), respectively. Eugenol is a botanical fungicide, which can be used as a green and environmentally friendly fungicide in the prevention and control of P. cuspidatum. This study reported for the first time that the pathogen of P. cuspidatum leaf spot was Ph. rhei. investigated the biological characteristics of the pathogen, and screened the indoor chemicals, which provided a theoretical basis for the prevention and control of P. cuspidatum leaf spot in production.

Structural dynamics of polycrystalline graphene.

The exceptional properties of the two-dimensional material graphene make it attractive for multiple functional applications, whose large-area samples are typically polycrystalline. Here, we study the mechanical properties of graphene in computer simulations and connect these to the experimentally relevant mechanical properties. In particular, we study the fluctuations in the lateral dimensions of the periodic simulation cell. We show that over short timescales, both the area A and the aspect ratio B of the rectangular periodic box show diffusive behavior under zero external field during dynamical evolution, with diffusion coefficients D_{A} and D_{B} that are related to each other. At longer times, fluctuations in A are bounded, while those in B are not. This makes the direct determination of D_{B} much more accurate, from which D_{A} can then be derived indirectly. We then show that the dynamic behavior of polycrystalline graphene under external forces can also be derived from D_{A} and D_{B} via the Nernst-Einstein relation. Additionally, we study how the diffusion coefficients depend on structural properties of the polycrystalline graphene, in particular, the density of defects.

The Role of RAD6B and PEDF in Retinal Degeneration.

RAD6B is an E2 ubiquitin-conjugating enzyme, playing an important role in DNA damage repair, gene expression, senescence, apoptosis and protein degradation. However, the specific mechanism between ubiquitin and retinal degeneration requires more investigation. Pigment epithelium-derived factor (PEDF) has a potent neurotrophic effect on the retina, protecting retinal neurons and photoreceptors from cell death caused by pathological damage. In this study, we found that loss of RAD6B leads to retinal degeneration in mice, especially in old age. Affymetrix microarray analysis showed that the PEDF signal was changed in RAD6B deficient groups. The expression of γ-H2AX, ß-Gal, P53, Caspase-3, P21 and P16 was increased significantly in retinas of RAD6B knockout (KO) mice. Our studies suggest that RAD6B and PEDF play an important role in the health of retina, whereas the absence of RAD6B accelerates the degeneration.

Overexpression of thioredoxin reductase 1 can reduce DNA damage, mitochondrial autophagy and endoplasmic reticulum stress in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Several factors, including neuroinflammation, neuronal excitotoxicity, genetic mutations and incorrect protein folding are involved in PD pathophysiology. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. A growing body of research suggests that oxidative stress is a major factor in PD. Therefore, antioxidant therapy is an important approach for treating PD. The thioredoxin system is an important antioxidant system, and thioredoxin reductase 1 (TR1) is a major member of the thioredoxin system. The present study demonstrates that oxidative stress is increased and that the expression of TR1 is decreased in the SNc of A53T mice; TR1 has emerged as an important antioxidant agent in dopaminergic neurons. Therefore, we over-expressed TR1 in the MPP+-induced cellular model and in the A53T transgenic mouse model of PD. We confirmed that the overexpression of TR1 in neuronal cells decreased DNA damage and malondialdehyde (MDA) and ROS generation, increased T-SOD and GSH production, and decreased the ER stress, and autophagy in the PD model. In summary, our findings demonstrate that the overexpression of TR1 could be effective as a novel neuroprotective strategy for PD. This research suggests a novel direction in the treatment of PD.

Protective effect of thioredoxin reductase 1 in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Many factors can explain the mechanism. However, the precise mechanism that contributes to the decreased number of dopaminergic neurons is unknown. Our study shows that oxidative stress is increased in models of PD compared with WT mice; Thioredoxin reductase 1(TR1) has emerged as an important antioxidant agent in dopaminergic neurons. In summary, our findings demonstrate that the overexpression of TR1 could be developed into a novel neuroprotective strategy for PD and that the reduction of the expression of GSK-3ß and NF-κB could also be promising therapeutic strategies for PD. This research suggests a new direction in the treatment of PD.

Mitigating self-excited thermoacoustic oscillations in a liquid fuel combustor using dual perforated plates.

Perforated plates are widely used in many practical burners to attenuate noise emissions. In this study, the acoustic absorption capability of dual perforated plates (DPPs) with different porosities and aperture diameters was evaluated and tested in an impedance tube, and the damping performance of the DPPs located in a liquid fuel combustor inlet section was experimentally studied. The DPPs have an adjustable first cavity and can mitigate the thermoacoustic oscillations within a wide sound absorption bandwidth. The DPPs can absorb 95% of the specified incident sound energy. The combustion results indicated that the installation of DPPs at the inlet section has two effects: sound attenuation and the frequency shift of the combustor. The maximum reduction in dynamic pressure and CH* chemiluminescence intensity inside the chamber were 14 and 19 dB, respectively. When the primary air flow rate deviates from the optimal value, the DPPs can reduce the pressure amplitude in the combustion chamber by almost 80%. In general, this study may promote the application of DPPs under bias flow for the stabilization of spray combustion.

Frequent intra- and inter-species introgression shapes the landscape of genetic variation in bread wheat.

BACKGROUND: Bread wheat is one of the most important and broadly studied crops. However, due to the complexity of its genome and incomplete genome collection of wild populations, the bread wheat genome landscape and domestication history remain elusive. RESULTS: By investigating the whole-genome resequencing data of 93 accessions from worldwide populations of bread wheat and its diploid and tetraploid progenitors, together with 90 published exome-capture data, we find that the B subgenome has more variations than A and D subgenomes, including SNPs and deletions. Population genetics analyses support a monophyletic origin of domesticated wheat from wild emmer in northern Levant, with substantial introgressed genomic fragments from southern Levant. Southern Levant contributes more than 676 Mb in AB subgenomes and enriched in the pericentromeric regions. The AB subgenome introgression happens at the early stage of wheat speciation and partially contributes to their greater genetic diversity. Furthermore, we detect massive alien introgressions that originated from distant species through natural and artificial hybridizations, resulting in the reintroduction of ~ 709 Mb and ~ 1577 Mb sequences into bread wheat landraces and varieties, respectively. A large fraction of these intra- and inter-introgression fragments are associated with quantitative trait loci of important traits, and selection events are also identified. CONCLUSION: We reveal the significance of multiple introgressions from distant wild populations and alien species in shaping the genetic components of bread wheat, and provide important resources and new perspectives for future wheat breeding.

A heterometallic metal-organic framework based on multi-nuclear clusters exhibiting high stability and selective gas adsorption.

The design and synthesis of porous heterometallic metal-organic frameworks (MOFs) with high thermal and chemical stability is a challenging task at present. In this work, by the heterometallic cooperative crystallization (HCC) approach, an original heterometallic MOF based on a tetra-carboxylic ligand has been solvothermally synthesized [In6O3Tb3O(CBDA)3]·18DMF·3H2O (In/Tb-CBDA) [CBDA = 5,5'-(carbonylbis(azanediyl))-diisophthalic acid, DMF = N,N-dimethylformamide]. The framework of In/Tb-CBDA is cooperatively assembled from the rarely reported tetra-nuclear In4O2(COO)4 and tri-nuclear Tb3O(COO)6 clusters, and an organic ligand. Topological analysis indicates that In/Tb-CBDA exhibits a new (4,4,6)-connected topology with the Schläfli symbol (4·63·82)6(43·69·83)2(62·84)3. Noteworthy, forming multi-nuclear metal clusters prompts the framework to maintain high stability under the conditions of heating to 150 °C, exposure to air, and soaking in acidic and basic aqueous solutions for 12 h. After desolvation, In/Tb-CBDA shows permanent porosity proved by N2 adsorption isotherms. In addition, theoretical ideal adsorption solution theory (IAST) calculation indicates that In/Tb-CBDA displayed high selective adsorption of CO2/CH4, C2H6/CH4 and C3H8/CH4 at room temperature. This work shows a striking example of a porous heterometallic MOF material with high thermal and chemical stability, which exhibits high-efficiency selective gas adsorption behaviour.

Current progress in the controlled synthesis and biomedical applications of ultrasmall (<10 nm) NaREF4 nanoparticles.

The design and fabrication of rare earth upconversion nanoparticle (UCNP)-based nanomedical platforms have evoked increasing interest. However, their bio-safety is always the most worrisome problem. Most nanoparticles can accumulate in the internal organs, leading to acute toxicity, a long-term inflammatory response, or even fibrosis and cancer. In contrast, ultrasmall (sub-10 nm) nanoparticles have minimal safety risk because they can escape from macrophages, pass biological barriers, and be easily degraded or excreted from the body. In this review, we mainly introduce new progress in preparation strategies, imaging and drug delivery with regards to ultrasmall UCNPs, with an emphasis on rare earth fluorides, NaREF4. Finally, we discuss the future outlook and challenges relating to ultrasmall UCNPs.

Comparative neonatal outcomes in singleton births from blastocyst transfers or cleavage-stage embryo transfers: a systematic review and meta-analysis.

BACKGROUND: Comparative neonatal outcomes with respect to singleton births from blastocyst transfers or cleavage-state embryo transfers are controversial with respect to which method is superior. Many studies have yielded contradictory results. We performed a systematic review and meta-analysis for the purpose of comparing neonatal outcomes in single births following IVF/ICSI. METHODS: We searched the Medline, Embase and Cochrane Central Register of Clinical Trials (CCTR) databases until October 2016. Studies and trials that contained neonatal outcomes for singleton births were included. Data were extracted in 2 × 2 tables. The analysis was performed using Rev Man 5.1 software. Risk ratios (RRs) and risk differences, with 95% confidence intervals, were calculated to assess the results of each outcome. Subgroups were applied in all outcomes. Newcastle-Ottawa scale (NOS) checklists were used to assess the quality of the referenced studies. RESULTS: Twelve studies met the criteria in this meta-analysis. There was a high risk of preterm birth after blastocyst embryo transfer versus the risk after cleavage-stage transfer (RR: 1.11, 95% CI: 1.01-1.22). For the "only fresh" subgroup, the outcome was coincident (RR: 1.16, 95% CI: 1.06-1.27). For the "fresh and frozen" and "only frozen" subgroups, there were no differences. Patients who received fresh blastocyst embryo transfers had a high risk of very preterm births (RR: 1.16, 95% CI: 1.02-1.31). Finally, cleavage-stage embryo transfers were associated with a high risk of infants who were small for gestational age (0.83, 95% CI: 0.76-0.92) and a low risk of those who were large for gestation age (1.14, 95% CI: 1.04-1.25). CONCLUSIONS: The risks of preterm and very preterm births increased after fresh blastocyst transfers versus the risks after fresh cleavage-stage embryo transfers. However, in frozen embryo transfers, there were no differences. Blastocyst embryo transfers resulted in high risks of infants who were large for gestational age, and cleavage-stage embryo transfers resulted in high risks of infants who were small for gestational age.

[Effect of Gegen Qinlian decoction on hepatic cytochrome CYP450 isozymes in rats by HPLC-MS/MS].

To study the effect of Gegen Qinlian decoction and its major effective components on five hepatic microsomal CYP450 isozymes in rats. The in vitro hepatic microsomal incubation technique was used to co-culture Gegen Qinlian decoction and its major effective components together with each probe substrate. HPLC-MS/MS was used to establish the analytical method for metabolites of the five isoform probe substrates of CYP450 isozymes, detect the linearity among micoromal protein concentration, incubation time and metabolite formation amount. And HPLC-MS/MS was applied to determine the formation rate (V) of corresponding metabolites (acetaminophen, 4-OH-chlorzoxazone, dextrophan, 6-OH-chlorzoxazone and 6ß-hydroxytestosterone) specific probe substrates of the five isoform probe substrates of CYP450 isozymes (phenacetin, polbutamide, dextromethorphan, chlorzoxazone, testosterone), in order to determine the activity of each isozyme. The result showed good linearity among acetaminophen, 4-OH-tolbutamide, dextrophan, 6-OH-chlorzoxazone and 6ß-hydroxytestosterone, satisfactory precision, stability and average recovery, suggesting the method was feasible. The optimized in vitro microsomal incubation conditions conformed to the requirements in the guideline of drug-drug interaction. Gegen Qinlian decoction showed different degrees of inhibitor effect on 5 CYP450 isoforms (CYP1A2, CYP2C11, CYP2D2, CYP2E1, CYP3A1/2). Its major effective component berberine could inhibit each CYP450 isoform at high concentrations (except for CYP1A2, CYP3A1/2).

Spatial memory impairment is associated with hippocampal insulin signals in ovariectomized rats.

Estrogen influences memory formation and insulin sensitivity. Meanwhile, glucose utilization directly affects learning and memory, which are modulated by insulin signals. Therefore, this study investigated whether or not the effect of estrogen on memory is associated with the regulatory effect of this hormone on glucose metabolism. The relative expression of estrogen receptor ß (ERß) and glucose transporter type 4 (GLUT4) in the hippocampus of rats were evaluated by western blot. Insulin level was assessed by ELISA and quantitative RT-PCR, and spatial memory was tested by the Morris water maze. Glucose utilization in the hippocampus was measured by 2-NBDG uptake analysis. Results showed that ovariectomy impaired the spatial memory of rats. These impairments are similar as the female rats treated with the ERß antagonist tamoxifen (TAM). Estrogen blockade by ovariectomy or TAM treatment obviously decreased glucose utilization. This phenomenon was accompanied by decreased insulin level and GLUT4 expression in the hippocampus. The female rats were neutralized with hippocampal insulin with insulin antibody, which also impaired memory and local glucose consumption. These results indicated that estrogen blockade impaired the spatial memory of the female rats. The mechanisms by which estrogen blockade impaired memory partially contributed to the decline in hippocampal insulin signals, which diminished glucose consumption.

Downregulation of thioredoxin reductase 1 expression in the substantia nigra pars compacta of Parkinson's disease mice.

Because neurons are susceptible to oxidative damage and thioredoxin reductase 1 is extensively distributed in the central nervous system and has antioxidant properties, we speculated that the enzyme may be involved in the pathogenesis of Parkinson's disease. A Parkinson's disease model was produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into C57BL/6 mice. Real-time reverse transcription-PCR, western blot analysis and colorimetric assay showed that the levels of thioredoxin reductase 1 mRNA and protein were decreased, along with a significant reduction in thioredoxin reductase activity, in the midbrain of Parkinson's disease mice compared with normal mice. Immunohistochemical staining revealed that the number of thioredoxin reductase 1-positive neurons in the substantia nigra pars compacta of Parkinson's disease mice was significantly decreased compared with normal mice. These experimental findings suggest that the expression of thioredoxin reductase 1 in the substantia nigra pars compacta of Parkinson's disease mice is significantly decreased, and that the enzyme may be associated with disease onset.