Effects of preheat treatment and syringic acid modification on the structure, functional properties, and stability of black soybean protein isolate.

This study investigated preheated (25-100°C) black soybean protein isolate (BSPI) conjugated with syringic acid (SA) (25 and 50 µmol/g protein) under alkaline conditions, focusing on the structure, functional properties, and storage stability. The results revealed that the SA binding equivalent and binding rate on BSPI increased continuously as the preheat temperature increased. Additionally, preheating positively impacted the surface hydrophobicity (H0) of BSPI, with further enhancement observed upon SA binding. Preheating and SA binding altered the secondary and tertiary structure of BSPI, resulting in protein unfolding and increased molecular flexibility. The improvement in BSPI functional properties was closely associated with both preheating temperature and SA binding. Specifically, preheating decreased the solubility of BSPI but enhanced the emulsifying activity index (EAI) and foaming capacity (FC) of BSPI. Conversely, SA binding increased the solubility of BSPI with an accompanying increase in EAI, FC, foaming stability, and antioxidant activity. Notably, the BSPI100-SA50 exhibited the most significant improvement in functional properties, particularly in solubility, emulsifying, and foaming attributes. Moreover, the BSPI-SA conjugates demonstrated good stability of SA during storage, which positively correlated with the preheating temperature. This study proposes a novel BSPI-SA conjugate with enhanced essential functional properties, underscoring the potential of preheated BSPI-SA conjugates to improve SA storage stability. PRACTICAL APPLICATION: Preheated BSPI-SA conjugates can be used as functional ingredients in food or health products. In addition, preheated BSPI shows potential as a candidate for encapsulating and delivering hydrophobic bioactive compounds.

Actinomyces meyeri-induced brain abscess in pregnancy: a case report.

BACKGROUND: Brain abscesses can occur when suppurative, bacterial or protozoan infections spread to the brain. Here, we report a rare case of Actinomyces meyeri-induced brain abscess in a pregnant woman. CASE PRESENTATION: We present the case of a 38-years-old primipara admitted to the emergency department at our hospital with a 4-day history of fever and vomiting. The symptoms worsened rapidly during the 8 h prior to admission, and the patient experienced a sudden loss of consciousness 4 h before arrival to the unit. Brain magnetic resonance imaging revealed abnormal signals in the right parietal-temporal lobe, suggesting the possibility of abscess rupture into the ventricle and sulcus. Right lateral ventricle compression and midline structure deviation to the left were noted. A right temporal-occipital mass with midline shift was detected. Emergency procedures were promptly performed, including craniotomy, removal of the right temporal-occipital mass, decompressive craniectomy, implantation of an intracranial pressure monitoring device, and external ventricular drainage. Cerebrospinal fluid culture indicated infection with Actinomyces meyeri. After administration of antibiotics, including linezolid and meropenem injections, along with treatments to decrease intracranial pressure, the patient's vital signs stabilized. However, the patient developed hydrocephalus, requiring placement of a hydrocephalus shunt several months later. Throughout this period, the patient remained in a coma vigil state, and labor was induced for the fetus. CONCLUSIONS: Although the patient did not present with any apparent predisposing causes for brain abscess, a scout view of CT revealed dental caries. In addition, the occurrence of the brain abscess may have been influenced by the hormonal changes during pregnancy, including increased secretion of estrogen and progesterone, as well as decreased immune function. Early diagnosis and intervention are crucial in such cases. Therefore, it is recommended to seek early medical attention if symptoms such as fever, vomiting, and changes in mental state occur during pregnancy, as the prognosis for both the mother and infant is poor once the abscess ruptures.

Aerobic glycolysis is the predominant means of glucose metabolism in neuronal somata, which protects against oxidative damage.

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.

Changes in phenolic compounds and antioxidant activities of "nine steaming nine sun-drying" black soybeans before and after in vitro simulated gastrointestinal digestion.

Black soybean (Glycine max (L.) Merr.) is rich in phenolic compounds, and processing technology has a significant effect on the content and activity of phenolic compounds. However, the mechanism of nine steaming and nine sun-drying processing technique is not fully understood. This paper presents the changes of phenolics content, phenolic acids composition and their influence on antioxidant activity before and after in vitro simulated gastrointestinal digestion of black soybeans (BS) under the process of nine steaming nine sun-drying. Results showed that the total phenolic content (TPC) and total flavonoids content (TFC) in BS were reduced by the heat treatment method, and exhibited a decreasing trend with more steaming and sun-drying cycle. During in vitro digestion, the contents and bioaccessibility of 12 phenolic acids (PA-12) in BS were highest in the stomach, followed by mouth and the intestine. The bioaccessibility of PA-12 in steamed and sun-dried BS was higher than that of raw black soybeans (S0D0) after digestion. It reached maximum after digestion at the third steaming and sun-drying cycle (i.e. S3D3), wherein the phenolic acids with the highest bioaccessibility were syringic acid, gallic acid, ferulic acid and chlorogenic acid. Syringic acid, in particular, increased significantly during digestion compared with that before digestion, which also increased during processing. The antioxidant activity of in vitro digested BS products with appropriate steaming and sun-drying degree increased compared with S0D0. Principal component analysis (PCA) showed that the in vitro digestion-induced properties of steamed and sun-dried BS could be well distinguished. The results confirm that the phenolic compounds and bioaccessibility of nine steamed nine sun-dried BS must be taken into account when assessing the improvement of human health.

Spatiotemporal Differentiation and Driving Force Analysis of the High-Quality Development of Urban Agglomerations along the Yellow River Basin.

The ecological protection and high-quality development (HQD) of the Yellow River Basin (YRB) have been promoted as national strategies. An urban agglomeration is the basic unit of the YRB used to participate in international competitions. Taking seven urban agglomerations covering 70 cities along the YRB as the sample, this paper establishes a high-quality evaluation system and uses the entropy method and exploratory spatial data analysis (ESDA) to analyze the HQD levels of the seven urban agglomerations along the YRB from 2009 to 2018. In addition, geographically-weighted regression (GWR) is adopted to analyze the influencing factors. The results show that: (1) the gap in the HQD of the seven urban agglomerations gradually narrows, showing a spatial pattern of "high in the east, low in the west, and depression in the middle"; (2) the HQD levels of the seven urban agglomerations have a strong spatial correlation, and the patterns of cold and hot spots have not changed substantially, showing the spatial distribution of "hot in the east, cold in the west"; (3) the degree of influence of each driving factor on the HQD differs among the seven urban agglomerations. The order is as follows: industrial structure upgrading index > proportion of R&D expenditure > urbanization rate > internet penetration rate > proportion of urban construction area > proportion of days reaching the air standard. These findings show that advanced industrial structure and technology are the two core driving forces for the HQD of the urban agglomerations along the YRB.

Optogenetic control of small GTPases reveals RhoA mediates intracellular calcium signaling.

Rho/Ras family small GTPases are known to regulate numerous cellular processes, including cytoskeletal reorganization, cell proliferation, and cell differentiation. These processes are also controlled by Ca2+, and consequently, cross talk between these signals is considered likely. However, systematic quantitative evaluation has not yet been reported. To fill this gap, we constructed optogenetic tools to control the activity of small GTPases (RhoA, Rac1, Cdc42, Ras, Rap, and Ral) using an improved light-inducible dimer system (iLID). We characterized these optogenetic tools with genetically encoded red fluorescence intensity-based small GTPase biosensors and confirmed these optogenetic tools' specificities. Using these optogenetic tools, we investigated calcium mobilization immediately after small GTPase activation. Unexpectedly, we found that a transient intracellular calcium elevation was specifically induced by RhoA activation in RPE1 and HeLa cells. RhoA activation also induced transient intracellular calcium elevation in MDCK and HEK293T cells, suggesting that generally RhoA induces calcium signaling. Interestingly, the molecular mechanisms linking RhoA activation to calcium increases were shown to be different among the different cell types: In RPE1 and HeLa cells, RhoA activated phospholipase C epsilon (PLCε) at the plasma membrane, which in turn induced Ca2+ release from the endoplasmic reticulum (ER). The RhoA-PLCε axis induced calcium-dependent nuclear factor of activated T cells nuclear translocation, suggesting that it does activate intracellular calcium signaling. Conversely, in MDCK and HEK293T cells, RhoA-ROCK-myosin II axis induced the calcium transients. These data suggest universal coordination of RhoA and calcium signaling in cellular processes, such as cellular contraction and gene expression.

Sludge-based activated carbon catalyzed H2O2 oxidation of reactive azo dyes.

Sludge-based activated carbon (ZAC) was successfully employed as both adsorbent and catalyst for the oxidation process of reactive yellow 86 (RY86) and reactive black 5 (RB5). Physicochemical properties of the prepared sewage sludge-derived activated carbon were evaluated by N2 adsorption/desorption, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The effects of parameters such as initial pH, H2O2 concentrations, ZAC dosages, dye concentrations and temperature on the removal of RY86 and RB5 were investigated. Kinetics results showed that the adsorption rates of RY86 and RB5 by ZAC can be approximated by the pseudo-first order model, and that the oxidation rates by Behnajady-Modirshahla-Ghanbery (BMG) model. Under the optimum conditions in the experiment, i.e. pH = 6.0, T = 303 K, [H2O2] = 49.5 mmol/L, [ZAC] = 4 g/L, [dyes] = 300 mg/L and t = 150 min, 99%, 88% and 84% of colour, COD and TOC were removed by Fenton -like oxidation for RY86, while for RB5, the three removal rates were 90%, 70% and 62%, respectively, indicating that sludge-based activated carbon can be used as an effective catalyst to oxidation of dyes by H2O2 from coloured wastewater.

Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors.

Parasitic diseases cause ∼ 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs.

Trypanosoma cruzi infection and host lipid metabolism.

Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several metabolic pathways. We reviewed the interaction of T. cruzi with each of the relevant host components, in order to further understand the roles of host lipid metabolism in T. cruzi infection. This review sheds light on the potential impact of T. cruzi infection on the status of host lipid homeostasis.

Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment.

BACKGROUND: Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains an important public health issue in many Central and South American countries, as well as non-endemic areas with high rates of immigration from these countries. Existing treatment options for CD are limited and often unsatisfactory. Moreover the lack of post-treatment tests of cure limits the development of new drugs. To address this issue, we sought to identify serum biomarkers following nifurtimox (Nfx) treatment that could be used as an early test of cure and/or markers of a therapeutic response. METHODS: Human sera from Chagas patients pre- and post-treatment with Nfx (n = 37) were compared to samples from healthy subjects (n = 37) using a range of proteomic and immunologic techniques. Biomarker peaks with the best discriminatory power were further characterized. RESULTS: Using serum samples (n = 111), we validated the presence of five key biomarkers identified in our previous study, namely human apolipoprotein A-I (APOA1) and specific fragments thereof and one fragment of human fibronectin (FN1). In chagasic serum samples all biomarkers except full-length APOA1 were upregulated. These five biomarkers returned to normal in 43% (16/37) of the patients treated with Nfx at three years after treatment. CONCLUSIONS: The normalization of biomarker patterns strongly associated with CD suggests that these markers can be used to identify patients in whom Nfx treatment is successful. We believe that these are the first biomarkers predictive of cure in CD patients.

Apolipoprotein A-I truncations in Chagas disease are caused by cruzipain, the major cysteine protease of Trypanosoma cruzi.

Trypanosoma cruzi is the etiologic agent of Chagas disease. Approximately 10 million people are infected worldwide. We have previously reported that in individuals infected with T. cruzi, apolipoprotein A-I (Apo A-I), the major structural component of host high-density lipoprotein, was truncated into fragments that are specific to Chagas disease and have the potential to be used as diagnostic biomarkers. We investigated the possibility that cruzipain, the major cysteine protease of T. cruzi, is responsible for truncating host Apo A-I. We found that due to Apo A-I truncation, the high-density lipoprotein subspecies profile is altered in individuals with Chagas disease compared with healthy controls. Western blot analysis revealed that both purified Apo A-I protein and Apo A-I in the high-density lipoprotein complex were susceptible to cruzipain cleavage, and the sizes of the truncation product in the latter matched the sizes of Apo A-I biomarkers. We also found that in vitro feeding T. cruzi-infected differentiated human adipocytes with purified human high-density lipoprotein led to the appearance of the biomarker fragments of Apo A-I. Cruzipain is found both on the cytoplasmic membrane and in the internal lysosomal structure of T. cruzi. We demonstrate that cruzipain from both sources contributes to the production of Apo A-I truncation in the biomarker set.

Association between physical activity and serum C-peptide levels among the elderly.

AIM: Serum C-peptide is an active peptide that has important physiological functions and characteristics in the elderly. The present study aimed to investigate the association between physical activity and serum C-peptide level independent of insulin level among the elderly. METHODS: The study included 1700 elderly participants aged ≥ 65 years. Stratified analysis of covariance was used to compare serum C-peptide levels in participants with different physical activity levels. Two separate multiple linear regression models were created to estimate the association between physical activity and serum C-peptide level. RESULTS: The results of analysis of covariance stratified by sex, body mass index and serum insulin level showed that those who engaged in vigorous physical activity had lower serum C-peptide levels than those who engaged in light or no physical activity. Separate multiple linear regression analysis showed that in those with low serum C-peptide levels (≤ 0.621 nmol/L), physical activity was significantly positively associated with the serum C-peptide level. In contrast, physical activity was negatively associated with the serum C-peptide level among those with serum C-peptide level >0.621 nmol/L. CONCLUSIONS: The serum C-peptide level showed a significant two-way association with physical activity. The present findings suggest that physical activity modification is important for improving serum C-peptide levels among the elderly.

Serological and parasitological response in chronic Chagas patients 3 years after nifurtimox treatment.

BACKGROUND: With declining vectorial transmission, Chagas disease predominantly affects adults nowadays. The efficacy of nifurtimox in the chronic phase in adult patients is poorly known, particularly in regions where there is no risk of reinfection. Recommendations for treatment outcome assessment rely on serological follow-up. We evaluated the serological and parasitological response to nifurtimox in a cohort of adult patients three years post-treatment in Switzerland. METHODS: Patients treated with nifurtimox in 2008 during a cross-sectional study in Geneva, Switzerland, were contacted for follow-up in 2011. Two ELISAs and a rapid immunochromatographic test were used to test 2008 and 2011 serum samples simultaneously. In addition, conventional and real-time PCR were performed on 2011 samples. RESULTS: Thirty-seven (84.1%) of 44 eligible patients, predominantly female, middle-aged, Bolivians at the indeterminate stage, were enrolled. All 2011 ELISA and immunochromatographic tests were positive. Twenty-eight (75.7%) patients presented a lower optical density (OD) in 2011 compared to 2008. This OD difference was significant in both commercial (P < 0.001) and in-house (P = 0.002) ELISAs. Agreement between the two ELISAs was low (Kappa = 0.469). All patients had negative conventional PCR results but one (2.7%) was positive with real-time PCR. CONCLUSION: Our results highlight the inadequacy of serology for assessing response in adults, three years after treatment. In our cohort, 97.3% had results that could either indicate treatment failure or persistant humoral response despite treatment. The lack of accurate early post-treatment tests of cure prevents appropriate patients information and councelling. New follow-up tests are needed to assess treatments efficacy given the large adult population in need of antiparasitic therapy.

Genetic control of high density lipoprotein-cholesterol in AcB/BcA recombinant congenic strains of mice.

Epidemiological studies show that high HDL-cholesterol (HDLc) decreases the risk of cardiovascular disease. To map genes controlling lipid metabolism, particularly HDLc levels, we screened the plasma lipids of 36 AcB/BcA RC mouse strains subjected to either a normal or a high-fat/cholesterol diet. Strains BcA68 and AcB65 showed deviant HDLc plasma levels compared with the parental A/J and C57BL/6J strains; they were thus selected to generate informative F2 crosses. Linkage analyses in the AcB65 strain identified a locus on chromosome 4 (Hdlq78) responsible for high post-high fat diet HDLc levels. This locus has been previously associated at genome-wide significance to two regions in the human genome. A second linkage analysis in strain BcA68 identified linkage in the vicinity of a gene cluster known to control HDLc levels. Sequence analysis of these candidates identified a de novo, loss-of-function mutation in the ApoA1 gene of BcA68 that prematurely truncates the ApoA1 protein. The possibility of dissecting the specific effects of this new ApoA1 deficiency in the context of isogenic controls makes the BcA68 mouse a valuable new tool.