Association between plasma maresin 1 and the risk of atherosclerotic cardiovascular disease in Chinese adults: A community-based cohort study.

BACKGROUND AND AIMS: It has been reported that maresin 1 (MaR1) is able to protect against the development of atherogenesis in cellular and animal models. This study was performed to investigate whether plasma MaR1 is associated with the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. METHODS AND RESULTS: The study included 2822 non-ASCVD participants from a community-based cohort who were followed for about 8 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for ASCVD events according to baseline MaR1 quartiles were calculated using the Cox proportional hazards model. During follow-up, a total of 290 new ASCVD cases were identified. The restricted cubic spline analysis indicated a linear dose-response association between plasma MaR1 and incident ASCVD. In addition, the adjusted-HR (95% CI) for ASCVD events associated with one standard deviation increase in MaR1 was 0.79 (0.68-0.91). Moreover, the adjusted-HRs (95% CIs) for ASCVD events associated with the second, third and fourth quartiles versus the first quartile of plasma MaR1 were 1.00, 1.04 (0.76, 1.42), 0.88 (0.64, 1.22) and 0.58 (0.41, 0.84), respectively. Mediation analyses showed that the association between MaR1 and incident ASCVD was partially mediated by small dense low-density lipoprotein cholesterol, with a mediation proportion of 9.23%. Further, the net reclassification improvement and integrated discrimination improvement of ASCVD risk were significantly improved when MaR1 was added to basic model established by conventional risk factors (all p < 0.01). CONCLUSIONS: Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development.

Knowledge of Alzheimer's disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis.

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.

Meta-analysis of Palliative Care on End-stage Quality of Life in Cancer Patients.

Objective: This study aimed to investigate the impact of palliative care on the quality of life, depressive state, and physical and psychological symptoms of patients with end-stage cancer. Methods: A systematic literature search of PubMed, Embase, and Scopus databases was conducted for randomized controlled trials (RCTs) published from May 2000 to June 2023, focusing on the impact of palliative care on end-stage cancer patients. The search utilized terms such as "palliative care," "cancer/tumor/malignancy," "terminal/end-stage/advanced," to identify studies meeting our inclusion criteria. Selected RCTs were evaluated for quality, and relevant data were extracted for meta-analysis. Results: Meta-analysis of 16 RCTs revealed that palliative care significantly improved depressive states [OR=-0.88, 95%CI (-1.55, -0.20), P = .01] and alleviated physical and psychological symptoms [OR=-2.38, 95%CI (-3.95, -0.81), P = .003] in end-stage cancer patients compared to conventional oncology care. However, the improvement in overall quality of life was not statistically significant (P > .05). Conclusion: Palliative care significantly enhances the mental and physical well-being of end-stage cancer patients by reducing depressive states and symptom burden, although its impact on overall quality of life requires further exploration.

Palladium-Catalyzed Thiocarbonylation of Aryl Iodides Using CO2.

The first example of catalytic thiocarbonylation of aryl iodides using CO2 has been achieved employing a combination of PdCl2 and carbazole-derived phosphine ligands. Under mild conditions, a broad scope of aryl iodides were converted to the desired thioester products in the presence of aryl or alkyl thiols (33 examples, up to 96% yields). The choice of metal, ligands, and reductant were crucial for high efficiency and chemoselectivity. Moreover, this strategy provided an effective method for the late-stage functionalization of biorelevant molecules.

Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum.

Immunogenicity is a major issue associated with the PK, efficacy, and safety evaluation of therapeutic protein products during pre-clinical and clinical studies. A multi-tiered approach consisting of screening, confirmatory, and titration assays has been widely adopted for anti-drug antibody testing. GQ1001, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently linked to a cytotoxin of DM1, possesses a novel format of antibody-drug conjugates. In this study, we reported the development, validation, and application of an acid-dissociation bridging enzyme-linked immunosorbent assay for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The sensitivity of the screening assay was 126.141 ng/mL in undiluted serum. The screening assay and confirmatory assay were neither affected by the naïve monkey serum nor by 2% and 5% (v/v) erythrocyte hemolysates. Moreover, the assay was not subject to interference by 2500 ng/mL of human IgG1 in the samples. Drug interference at low positive control (150 ng/mL) and high positive control (8000 ng/mL) of anti-GQ1001 antibodies was not observed when GQ1001 concentrations were below 3.125 µg/mL and 100 µg/mL, respectively. Furthermore, no hook effect was observed for the positive antibodies in the concentration range of 8 to 64 µg/mL. The validated assay was, thereafter, successfully applied to a single-dose toxicity study of GQ1001. Anti-drug antibody positive rates among dosing animals and testing samples were reported, and no significant impact was found on toxicokinetic outcomes.

Nuclear factor Y participates in alcoholic liver disease by activating SREBP1 expression in mice.

Chronic and excessive alcohol consumption leads to alcoholic liver disease (ALD). However, the molecular mechanisms in the regulation of ALD have not been fully deciphered. Liver lipid accumulation is an important research direction in ALD. In this study, the physiological role of nuclear factor Y (NF-Y) in ALD and the related mechanisms were investigated using murine hepatocytes and an ethanol-induced liver injury mouse model. In this study, ethanol promoted hepatic NF-Y expression in a mouse model and Hepa1-6 mouse hepatocytes. Lentivirus-mediated NF-Y overexpression in Hepa1-6 cells markedly increased sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression compared with empty vector control cells. Conversely, CRISPR/Cas9-mediated knockdown of NF-Y subunit A (NF-YA) attenuated FASN and SREBP1 expression. Mechanistically, luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) analysis indicated that NF-Y activates the transcription of SREBP1 by directly binding to the CCAAT regulatory sequence motif in the promoter. Overall, our results reveal a previously unrecognized physiological function of NF-Y in ALD by activating sterol regulatory element-binding protein 1 (SREBP1). Modulation of hepatic NF-Y expression may therefore offer an attractive therapeutic approach to manage ALD.

Cascade Reaction of 2-Naphthols and Azirines: One-Pot Synthesis of C-3 Naphthol-Substituted Benzo[e]indoles.

A copper-catalyzed annulation of 3-aryl-2H-azirines with 2-naphthols has been developed for the rapid assembly of C-3-naphthol-substituted benzo[e]indoles in one pot. This cascade reaction was realized through dearomatic nucleophilic ring opening of azirine, intramolecular cyclization, and oxidative cross-dehydrogenative coupling to furnish the important unreported π-expanded naphthol/benzo[e]indole biaryls.

Insights into pH-dependent transformation of gibberellic acid in aqueous solution: Transformation pathway, mechanism and toxicity estimation.

Gibberellic acid (GA3) is widely used in agriculture and maybe transfer with groundwater flow, which is an endocrine disruptor, but few studies have focused on the transformation pathway and toxicity assessment of GA3 and its products. Here, GA3 and its transformation products in aqueous solution were identified and quantified by liquid chromatography mass spectrometry hybrid ion trap time-of-flight (LCMS-IT-TOF) and high-performance liquid chromatography (HPLC), respectively. The results showed that the half-life of GA3 transformation in ultrapure water was 16.1-24.6 days at pH=2.0-8.0, with the lowest half-life occurring at pH=8.0 and highest half-life occurring at pH=3.3. Isomerized gibberellic acid (Iso-GA3) and gibberellenic acid (GEA) were the main transformation products with a little hydroxy gibberellic acid (OH-GA3). In North China groundwater, the mass balance of GA3 and its products was 76.2%, including Iso-GA3 (58%), GEA (7.9%), GA3 (7.3%) and OH-GA3 (3%) after reaching transformation equilibrium. Using Gaussian 09 for chemical computation, it was found that the transformation mechanism of GA3 was dependent upon the bond energy and the stereochemical feature of its molecular structure. GA3 always isomerized from the γ-lactone ring due to the lowest bond energy between the oxygen terminus of the γ-lactone ring and A ring. While GA3 and its transformation products all had developmental toxicity, the predicated LC50 (96 hr) and LD50 of the main products of GA3 were much lower than those of GA3, indicating GA3 would be transformed into higher toxicity derivatives in water environments, posing a significant health risk to humans and the environment.

[Morin Improves Experimental Autoimmune Thyroiditis in Rats via NLRP3/Caspase-1 Pathway].

OBJECTIVE: To investigate the effects of morin-regulated NLRP3/Caspase-1 pathway on experimental autoimmune thyroiditis in rats. METHODS: The rats were randomly assigned to 6 groups: control group, experimental autoimmune thyroiditis group (EAT), low-, medium- and high-dose morin groups (post-modeling gavage of 50, 100 and 200 mg/kg morin hydrate per day for 6 weeks) and tripterygium wilfordii polyglycosides group (LGT group, post-modeling gavage of 6.25 mg/kg tripterygium wilfordii polyglycosidesper day for 6 weeks). Except for the control group, the rat model of experimental autoimmune thyroiditis was established by subcutaneous injection of 0.1 mL incomplete Freund's adjuvant containing porcine thyroglobulin. The levels of serum thyroglobulin (TgAb), thyroid peroxidase antibody (TPOAb), triiodothyronine (T3) and tetraiodothyronine (T4) in serum were detected by radioimmunoassay. The mRNA levels of interleukin-17 ( IL-17), interleukin-4 ( IL-4) and interferon γ ( INF- γ) were detected by reverse transcription-polymerase chain reaction. The levels of serum protein carbonyl content, 8-hydroxydeoxyguanosine (8-OHdG), and malondialdehyde (MDA) activity were checked with test kits. Expressions of NLRP3, apoptosis-related speck-like protein (ASC), and Caspase-1 were detected by Western blot. RESULTS: Compared with the EAT group, serum levels of TPOAb, TgAb, T3, and T4 in low-, medium- and high-dose Morin groups and LGT group were reduced ( P<0.01) and the mRNA levels of IL-17, INF-γ and IL-4 were increased ( P<0.01), the protein hydroxyl content, MDA activity, and 8-OHdG levels were reduced ( P<0.01). The levels of NLRP3, ASC and Caspase-1 were reduced ( P<0.01), the levels of 8-OHdG were significantly reduced ( P<0.01), and the levels of NLRP3, ASC and Caspase-1 were significantly reduced ( P<0.01). There were statistically significant differences between the data from the low-dose and the medium-dose Morin groups and the data of the LGT group ( P<0.05), while data from the high-dose Morin group showed no significant difference compared with the data of the LGT group. Data from low-, medium- and high-dose Morin groups showed no statistically significant differences ( P<0.05). CONCLUSION: The findings suggest that Morin improved experimental autoimmune thyroiditis in rats through regulating NLRP3/Caspase-1 pathway.

The N-Terminal Region of Soybean PM1 Protein Protects Liposomes during Freeze-Thaw.

Late embryogenesis abundant (LEA) group 1 (LEA_1) proteins are intrinsically disordered proteins (IDPs) that play important roles in protecting plants from abiotic stress. Their protective function, at a molecular level, has not yet been fully elucidated, but several studies suggest their involvement in membrane stabilization under stress conditions. In this paper, the soybean LEA_1 protein PM1 and its truncated forms (PM1-N: N-terminal half; PM1-C: C-terminal half) were tested for the ability to protect liposomes against damage induced by freeze-thaw stress. Turbidity measurement and light microscopy showed that full-length PM1 and PM1-N, but not PM1-C, can prevent freeze-thaw-induced aggregation of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes and native thylakoid membranes, isolated from spinach leaves (Spinacia oleracea). Particle size distribution analysis by dynamic light scattering (DLS) further confirmed that PM1 and PM1-N can prevent liposome aggregation during freeze-thaw. Furthermore, PM1 or PM1-N could significantly inhibit membrane fusion of liposomes, but not reduce the leakage of their contents following freezing stress. The results of proteolytic digestion and circular dichroism experiments suggest that PM1 and PM1-N proteins bind mainly on the surface of the POPC liposome. We propose that, through its N-terminal region, PM1 functions as a membrane-stabilizing protein during abiotic stress, and might inhibit membrane fusion and aggregation of vesicles or other endomembrane structures within the plant cell.

Trash to Treasure: Eco-Friendly and Practical Synthesis of Amides by Nitriles Hydrolysis in WEPPA.

The hydration of nitriles to amides in a water extract of pomelo peel ash (WEPPA) was realized with moderate to excellent yields without using external transition metals, bases or organic solvents. This reaction features a broad substrate scope, wide functional group tolerance, prominent chemoselectivity, and good reusability. Notably, a magnification experiment in this bio-based solvent at 100 mmol further demonstrated its practicability.

The association of depressive symptoms and medication adherence in asthma patients: The mediation effect of medication beliefs.

BACKGROUND: The significant role of depression in influencing medication beliefs, which are pivotal cognitive factors that strongly influence medication adherence, has been established. Poor adherence to asthma-controlled medication poses an significant barrier to achieving optimal asthma management. OBJECTIVE: To explore the potential mediating effects of medication beliefs on the relationship between depressive symptoms and medication adherence in patients with asthma. METHODS: Demographic and clinical characteristics, depressive symptoms, medication adherence, and medication beliefs were collected using questionnaires. Structural equation modeling, was utilized to model medication beliefs as mediators in the relationship between depressive symptoms and medication adherence. Bootstrapping was performed to analyze the mediation- and contrast-specific indirect effects of the two medication beliefs. RESULTS: Among the patients who participated in the study, 29.6 % with depressive symptoms were more prone to poor adherence and exhibited skepticism toward asthma medications. Depression had a direct effect (direct effect = -0.275, 95%CI: -0.369 to -0.190) and an indirect effect on adherence mediated by medication beliefs (indirect effect = -0.168, 95%CI: -0.224 to -0.121). The specific mediation effect of concern belief was stronger than that of necessity belief (difference = -0.076, 95%CI: -0.132 to -0.029). CONCLUSION: Depressive symptoms have a direct impact on medication adherence as well as an indirect effect mediated by beliefs about medication, particularly concerns belief.

Structure and properties of the acellular porcine cornea irradiated with 60Co-γ and electron beam and its histocompatibility.

Acellular porcine cornea (APC) has been used in corneal transplantation and treatment of the corneal diseases. Sterilization is a key step before the application of graft, and irradiation is one of the most commonly used methods. In this paper, APC was prepared by the physical freeze-thawing combined with biological enzymes, and the effects of the electron beam (E-beam) and cobalt 60 (60Co-γ) at the dose of 15 kGy on the physicochemical properties, structure, immunogenicity, and biocompatibility of the APC were investigated. After decellularization, the residual DNA was 20.86 ± 1.02 ng/mg, and the α-Gal clearance rate was more than 99%. Irradiation, especially the 60Co-γ, reduced the cornea's transmittance, elastic modulus, enzymatic hydrolysis rate, swelling ratio, and cross-linking degree. Meanwhile, the diameter and spacing of the collagen fibers increased. In the rat subcutaneous implantation, many inflammatory cells appeared in the unirradiated APC, while the irradiated had good histocompatibility, but the degradation was faster. The lamellar keratoplasty in rabbits indicated that compared to the E-beam, the 60Co-γ damaged the chemical bond of collagen to a larger extent, reduced the content of GAGs, and prolonged the complete epithelization of the grafts. The corneal edema was more serious within 1 month after the surgery. After 2 months, the thickness of the APC with the two irradiation methods tended to be stable, but that in the 60Co-γ group became thinner. The pathological results showed that the collagen structure was looser and the pores were larger, indicating the 60Co-γ had a more extensive effect on the APC than the E-beam at 15 kGy.

Structure and properties of the acellular porcine cornea irradiated with electron beam and its in-situ implantation.

Different sterilization doses of the electron beam (E-beam) will change the properties of biomaterials and affect their clinical application. Acellular porcine cornea (APC) is a promising corneal substitute to alleviate the shortage of corneal resources. The residual DNA was significantly reduced to 18.50 ± 3.19 ng/mg, and the clearance rate of α-Gal was close to 100% after the treatment with freezing-thawing combined enzyme, indicating that the decellularization was effective. The effects of different E-beam doses at 0, 2, 8, 15, and 25 kGy on the APC were studied. With the increase in irradiation dose, the transmittance, tensile strength, and swelling ratio of APC gradually decreased, but the resistance to enzymatic degradation was stronger than that of non-irradiated APC, especially at 8 kGy. The structure of APC was denser after irradiation, but the dose of 25 kGy could cause partial collagen fiber fracture and increase the pore size. The cell viability of the APC irradiated by 15 and 25 kGy were greater than 80%. After the implantation in rabbit corneas, there was no obvious neovascularization and inflammation, but the dose of 25 kGy had a more destructive effect on the chemical bonds of collagen, which made the APC easier to be degraded. The thickness of APC in the 25 kGy group was thinner than that in the 15 kGy group 1 year after surgery, and the epithelium grew more slowly, so the E-beam dose of 15 kGy might be more suitable for the sterilization of APC.

Long-term groundwater geochemical evolution induced by coal mining activities-a case study of floor confined limestone aquifer in Yaoqiao Coal Mine, Jiangsu, China.

Groundwater chemical composition can be changed due to long-term coal mining activities, but it was unclear how it was induced in Taiyuan Formation limestone (TFL) regarding the lack of relevant quantitative studies. The aim of this research is to improve understanding of the chemical composition changes in groundwater of L4 limestone in the coal mining area based on the available hydrochemical and hydrodynamical reports and studies during the period 1978-2020. The systematical analysis of the groundwater composition and field allows to make the hydrogeological characterization with the relatively independent blocks by the factor groups "Planar division & Vertical zonation" and "High water pressure, Poor recharge & Little water inflow," which determines different hydrochemical types and high TDS concentration. The long-term groundwater drainage has caused the eastern and southern limestone aquifer to demonstrate a wide range of depression cones and depletion of groundwater resources, the majority areas were dewatered, and the karstification process changed significantly. An analysis of chemical compositions changes due to extensive permanent drainage of L4 limestone water revealed the decrease in the TDS concentration. The solubility of calcite, dolomite, and gypsum changed, which resulted in the decreasing tendency of Ca2+ + Mg2+ ions. Evaporation and concentration were found to be the main factors determining the L4 limestone water composition, whereas ion exchange was the primary factor for rock-water interaction. These findings are helpful for mine enterprises to take necessary measures for preventing and controlling the groundwater quality degradation from the extensive coalmine drainage.

Boron-Assisted Cobalt-Catalyzed C-H Methylation Using CO2 and H2.

C-H methylation of heteroarenes (e.g., indoles, pyrroles, etc.) is frequently applied in the synthesis of drug/biorelated compounds. We herein report the use of CO2/H2 as a methylation reagent for selective C-H methylation of indoles and pyrroles in the presence of cobalt/B(C6F5)3 cocatalysts. The Lewis acidic additive B(C6F5)3 is essential to achieving good reactivity for a broad scope of substituted indoles and pyrroles (20 examples, up to 92% yields). The C-H methylation is accomplished via the CO2 reduction/C-C bond formation/reduction sequence. Water is the only byproduct. This system based on the use of non-noble metal catalysts features an environmentally benign alternative for C-H methylation.

Practical application for legacy acid mine drainage (AMD) prevention and treatment technologies in karst-dominated regions: A case study.

Acid mine drainage (AMD) from abandoned mines in karst-dominated regions in southwestern China was causing contamination of groundwater and surface streams. To avert the unwise decisions of "pollution first before treatment" during pre-mining, mid-mining and post-mining activities, this paper proposes a contaminant migration prevention technical framework covering 4 comprehensive processes. The formation mechanism of spring pollution, engineering remediation processes and contamination treatment effects were described in Longdong Spring. In 2018, the Longdong Spring water had Fe 33.83 mg/L and Mn 3.60 mg/L, exceeding the Chinese surface water standard (0.3 mg/L and 0.1 mg/L in GB 3838-2002) by 112 and 36 times, respectively. In 2020, after grout blocking, in situ treatment and wetland remediation, the highest Fe was 4.5 mg/L in a short period, and the spring water pollution days in this year were 42 days compared with the previous 320 spring water pollution days in 2018. In 2021, two years of remediation with the implementation of terminal remediation wetlands, the Fe was less than 0.03 mg/L compared with the previous 33.83 mg/L, and the water quality reached water standard (less than 0.3 mg/L). At present, Longdong Spring has become one of the most beautiful natural local landscapes.

Dissolved organic matter composition and fluorescence characteristics of the river affected by coal mine drainage.

Coal mine drainage (CMD) discharged into surface waters results in serious environmental pollution risk to rivers, lakes, and reservoirs. Coal mine drainage generally contains a variety of organic matter and heavy metals due to coal mining activities. Dissolved organic matter (DOM) plays an important role in the physicochemical and biological processes of many aquatic ecosystems. In this study, the investigations were carried out in the dry and wet seasons in 2021 to assess the characteristics of DOM compounds in coal mine drainage and the CMD-affected river. The results indicated that the pH of CMD-affected river pressed close to coal mine drainage. Besides, coal mine drainage lowered DO by 36% and increased total dissolved solids by 19% in the CMD-affected river. Coal mine drainage decreased absorption coefficient a(350) and absorption spectral slope S275-295 of DOM in the CMD-affected river; hence, DOM molecular size increased with decreasing S275-295. Three-dimensional fluorescence excitation-emission matrix spectroscopy and parallel factor analysis identified humic-like C1, tryptophan-like C2, and tyrosine-like C3 in the CMD-affected river and coal mine drainage. DOM in the CMD-affected river mainly originated from microbial and terrestrial sources, with strong endogenous characteristics. The ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry analysis revealed that coal mine drainage had a higher relative abundance of CHO (44.79%), with a higher unsaturation degree of DOM. Coal mine drainage decreased the AImod,wa, DBEwa (double bond equivalents), Owa, Nwa, and Swa values and increased the relative abundance of the O3S1 species with DBE of 3 and carbons number range of 15-17 at the CMD inlet to the river channel. Moreover, coal mine drainage with the higher protein content increased the protein content of water at the CMD inlet to the river channel and the downstream river. DOM compositions and proprieties in coal mine drainage were investigated to further understand the influence of organic matter on heavy metals in future study.

Serum metabolomics analysis in patients with alcohol dependence.

Objective: Alcohol dependence (AD) is a chronic recurrent mental disease caused by long-term drinking. It is one of the most prevalent public health problems. However, AD diagnosis lacks objective biomarkers. This study was aimed to shed some light on potential biomarkers of AD patients by investigating the serum metabolomics profiles of AD patients and the controls. Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to detect the serum metabolites of 29 AD patients (AD) and 28 controls. Six samples were set aside as the validation set (Control: n = 3; AD group: n = 3), and the remaining were used as the training set (Control: n = 26; AD group: n = 25). Principal component analysis (PCA) and partial least squares discriminant analysis (PCA-DA) were performed to analyze the training set samples. The metabolic pathways were analyzed using the MetPA database. The signal pathways with pathway impact >0.2, value of p <0.05, and FDR < 0.05 were selected. From the screened pathways, the metabolites whose levels changed by at least 3-fold were screened. The metabolites with no numerical overlap in their concentrations in the AD and the control groups were screened out and verified with the validation set. Results: The serum metabolomic profiles of the control and the AD groups were significantly different. We identified six significantly altered metabolic signal pathways, including protein digestion and absorption; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; linoleic acid metabolism; butanoate metabolism; and GABAergic synapse. In these six signal pathways, the levels of 28 metabolites were found to be significantly altered. Of these, the alterations of 11 metabolites changed by at least 3-fold compared to the control group. Of these 11 metabolites, those with no numerical overlap in their concentrations between the AD and the control groups were GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid and L-glutamine. Conclusion: The metabolite profile of the AD group was significantly different from that of the control group. GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid, and L-glutamine could be used as potential diagnostic markers for AD.

Transformation kinetics and mechanism of gibberellic acid with ferrihydrite: Building a novel adsorption-transformation multi-step kinetic model.

Gibberellic acid (GA3), a widely used phytohormone, is easily transformed into more toxic products. The soil and groundwater environment are an important sink for GA3, but its transformation catalyzed by soil minerals has not been studied. In this study, the transformation kinetics and mechanism of GA3 with ferrihydrite (Fh) were examined through kinetic batch experiments, microscopic-spectroscopic investigation and mathematical modeling. The results showed that rapid adsorption of GA3 on Fh occurred in the first 4 h, followed by a catalytic pseudo-first-order transformation of the parent compound and products generation (4 h-30 d). Fh predominantly enhanced the transformation of GA3 into Iso-GA3 which was further hydrolyzed into OH-GA3, in which adsorption was a prerequisite for transformation. The catalytic transformation likely resulted from the surface hydroxy of Fh, which not only stabilized the transformation intermediates by forming surface complexes with the carboxyl group of GA3 and its products, but also served as a powerful nucleophile to attack the γ-lactone of GA3 and Iso-GA3. Based on the catalytic isomerization and hydrolysis mechanism of GA3 with Fh, a novel adsorption-transformation multi-step kinetic conceptual model and mathematical model were developed. This model fitted the measured data well (R2 > 0.97) and the fitted parameters suggested that the transformation rate constants of the transformation of GA3 into Iso-GA3 and the transformation of Iso-GA3 into OH-GA3 were facilitated with Fh by ∼26 and ∼9 times, respectively. The multi-step kinetic model has great potential in simulating GA3 fate in soil and groundwater to assess its environmental health risk.