Molecular Mechanisms of Iron Transport and Homeostasis Regulated by Antarctic Krill-Derived Heptapeptide-Iron Complex.

In this study, the molecular mechanisms of iron transport and homeostasis regulated by the Antarctic krill-derived heptapeptide-iron (LVDDHFL-iron) complex were explored. LVDDHFL-iron significantly increased the hemoglobin, serum iron, total iron binding capacity levels, and iron contents in the liver and spleen to normal levels, regulated the gene expressions of iron homeostasis, and enhanced in vivo antioxidant capacity in iron-deficiency anemia mice (P < 0.05). The results revealed that iron ions within LVDDHFL-iron can be transported via the heme transporter and divalent metal transporter-1, and the absorption of LVDDHFL-iron involved receptor-mediated endocytosis. We also found that the transport of LVDDHFL-iron across cells via phagocytosis was facilitated by the up-regulation of the high mobility group protein, heat shock protein ß, and V-type proton ATPase subunit, accompanied by the regulatory mechanism of autophagy. These findings provided deeper understandings of the mechanism of LVDDHFL-iron facilitating iron absorption.

A Miniature Biomedical Sensor for Rapid Detection of Schistosoma japonicum Antibodies.

Schistosomiasis, typically characterized by chronic infection in endemic regions, has the potential to affect liver tissue and pose a serious threat to human health. Detecting and screening for this disease early on is crucial for its prevention and control. However, existing methods encounter challenges such as low sensitivity, time-consuming processes, and complex sample handling. To address these challenges, we report a soluble egg antigen (SEA)-based functionalized gridless and meander-type AlGaN/GaN high electron mobility transistors (HEMT) sensor for the highly sensitive detection of antibodies to Schistosoma japonicum. Immobilization of the self-assembled membrane on the gate surface was verified using a semiconductor parameter analyzer, scanning electron microscope (SEM), and atomic force microscopy (AFM). The developed biosensor demonstrates remarkable performance in detecting anti-SEA, exhibiting a linear concentration range of 10 ng/mL to 100 µg/mL and a sensitivity of 0.058 mA/log (ng/mL). It also exhibits similar excellent performance in serum systems. With advantages such as rapid detection, high sensitivity, miniaturization, and label-free operation, this biosensor can fulfill the requirements for blood defense.

Iron Complexes with Antarctic Krill-Derived Peptides Show Superior Effectiveness to Their Original Protein-Iron Complexes in Mice with Iron Deficiency Anemia.

Antarctic krill protein-iron complex and peptide-iron complex were acquired to investigate their iron bioavailability, expression of iron-regulated genes, and in vivo antioxidant capacity. Results indicated that the Antarctic krill peptide-iron complex significantly increased the hemoglobin (Hb), serum iron (SI), and iron contents in the liver and spleen in iron-deficiency anemia (IDA) mice (p < 0.05) compared with those of the Antarctic krill protein-iron complex. Despite the gene expressions of the divalent metal transporter 1(DMT1), the transferrin (Tf), and the transferrin receptor (TfR) being better regulated by both Antarctic krill peptide-iron complex and protein-iron complex, the relative iron bioavailability of the Antarctic krill peptide-iron complex group (152.53 ± 21.05%) was significantly higher than that of the protein-iron complex group (112.75 ± 9.60%) (p < 0.05). Moreover, Antarctic krill peptide-iron complex could enhance the antioxidant enzyme activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce the malondialdehyde (MDA) level in IDA mice compared with the protein-iron complex, and reduce the cell damage caused by IDA. Therefore, these results indicated that Antarctic krill peptide-iron complex could be used as a highly efficient and multifunctional iron supplement.

A highly sensitive sensor for carcinoembryonic antigen based on AlGaN/GaN high-electron-mobility transistors.

Carcinoembryonic antigen (CEA) is a well-known biomarker and validated serum biomarker for lung cancer. We introduce a simple label-free method for CEA detection. Specific recognition of CEA was made possible by immobilizing CEA antibodies in the sensing region of AlGaN/GaN high-electron-mobility transistors. The biosensors have a detection limit of 1 fg ml-1in phosphate buffer solution. This approach has advantages of integration, miniaturization, low cost, and rapid detection compared to other testing methods for lung cancer and could be used in future medical diagnostics.

Effects of sulforaphane on breast cancer based on metabolome and microbiome.

Sulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF-7 cell-transplanted nude mice with 50 mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate-related metabolites and glutathione-related metabolites and decreased tryptophan metabolites and methyl-purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate-reducing bacterium Desulfovibrio, which is related to reduced methylation capacity, and increased the genus Lactobacillus related to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.

Modulation effects of different treatments on periaqueductal gray resting state functional connectivity in knee osteoarthritis knee pain patients.

BACKGROUND: The analgesic effect of acupuncture is widely recognized, but the mechanical characteristics of acupuncture for pain relief, compared to non-steroidal anti-inflammatory (NSAIDs) and placebo medication, remain unknown. AIMS: To compare the modulation effects of acupuncture treatment with NSAIDs and placebo medication on descending pain modulation system (DPMS) in knee osteoarthritis (KOA) patients. METHODS: This study recruited 180 KOA patients with knee pain and 41 healthy controls (HCs). Individuals with KOA knee pain were divided randomly into groups of verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), and waiting list (WT), with 36 patients in each group. VA and SA groups included ten sessions of puncturing acupoints or puncturing non-acupoints acupuncture treatment for two successive weeks. Celecoxib capsules were continuously given orally to patients in the SC group at a dosage of 200 mg daily for 2 weeks. In the PB group, patients received a placebo capsule once a day for 2 weeks at the same dosage as celecoxib capsules. In the WL group, patients did not receive any treatment. Patients underwent a resting-state BOLD-fMRI scan pre- and post-receiving the therapy, whereas HCs only underwent a baseline scan. Seed (ventrolateral periaqueductal gray, vlPAG, a key node in DPMS) based resting-state functional connectivity (rs-FC) was applied in the data analysis. RESULTS: All groups demonstrated improved knee pain scores relative to the initial state. There was no statistical difference between the VA and SA groups in all clinical outcomes, and vlPAG rs-FC alterations. KOA knee pain individuals reported higher vlPAG rs-FC in the bilateral thalamus than HCs. KOA knee pain patients in the acupuncture group (verum + sham, AG) exhibited increased vlPAG rs-FC with the right dorsolateral prefrontal cortex (DLPFC) and the right angular, which is associated with knee pain improvement. In contrast with the SC and PB group, the AG exhibited significantly increased vlPAG rs-FC with the right DLPFC and angular. Contrary to the WT group, the AG showed greater vlPAG rs-FC with the right DLPFC and precuneus. CONCLUSIONS: Acupuncture treatment, celecoxib, and placebo medication have different modulation effects on vlPAG DPMS in KOA knee pain patients. Acupuncture could modulate vlPAG rs-FC with brain regions associated with cognitive control, attention, and reappraisal for knee pain relief in KOA patients, compared with celecoxib and placebo medication.

Iron delivery systems for controlled release of iron and enhancement of iron absorption and bioavailability.

Iron deficiency is a global nutritional problem, and adding iron salts directly to food will have certain side effects on the human body. Therefore, there is growing interest in food-grade iron delivery systems. This review provides an overview of iron delivery systems, with emphasis on the controlled release of iron during gastrointestinal digestion, as well as the enhancement of iron absorption and bioavailability. Iron-bearing proteins are easily degraded by digestive enzymes and absorbed through receptor-mediated endocytosis. Instead, protein aggregates are slowly degraded in the stomach, which delays iron release and serves as a potential iron supplement. Amino acids, peptides and polysaccharides can bind iron through iron binding sites, but the formed compounds are prone to dissociation in the stomach. Moreover, peptides and polysaccharides can deliver iron by mediating the formation of ferric oxyhydroxide which is absorbed through endocytosis or bivalent transporter 1. In addition, liposomes are unstable during gastric digestion and iron is released in large quantities. Complexes formed by polysaccharides and proteins, and microcapsules formed by polysaccharides can delay the release of iron in the gastric environment and prolong iron release in the intestinal environment. This review is conducive to the development of iron functional ingredients and dietary supplements.

A systematic review and meta-analysis of voxel-based morphometric studies of migraine.

OBJECTIVES: To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine. METHODS: Neuroimaging studies published from origin to August 1, 2021 were searched in six databases including PubMed, Web of Science, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP. Study selection, quality assessment, and data extraction were conducted by two independent researchers. Anisotropic effect size-signed differential mapping (AES-SDM) and activation likelihood estimation (ALE) were used to perform the meta-analysis of available studies reporting whole-brain gray matter (GM) structural data in migraine patients. Clinical variables correlation analysis and migraine subgroup analysis were also conducted. RESULTS: 40 articles were included after the strict screening, containing 1616 migraine patients and 1681 matched healthy subjects (HS) in total. Using the method of AES-SDM, migraine patients showed GM increase in the bilateral amygdala, the bilateral parahippocampus, the bilateral temporal poles, the bilateral superior temporal gyri, the left hippocampus, the right superior frontal gyrus, and the left middle temporal gyrus, as well as GM decrease in the left insula, the bilateral cerebellum (hemispheric lobule IX), the right dorsal medulla, the bilateral rolandic operculum, the right middle frontal gyrus, and the right inferior parietal gyrus. Using the method of ALE, migraine patients showed GM increase in the left parahippocampus and GM decrease in the left insula. The results of correlation analysis showed that many of these brain regions were associated with migraine headache frequency and migraine disease duration. Migraine patients in different subtypes (such as migraine without aura (MwoA), migraine with aura (MwA), episodic migraine (EM), chronic migraine (CM), vestibular migraine (VM), etc.), and in different periods (in the ictal and interictal periods) presented not entirely consistent GM alterations. CONCLUSION: Migraine patients have GM alterations in multiple brain regions associated with sensation, affection, cognition, and descending modulation aspects of pain. These changes might be a consequence of repeated migraine attacks. Further studies are required to determine how these GM changes can be used to diagnose, monitor disease progression, or exploit potential therapeutic interventions for migraine patients.

Exploration of iron-binding mode, digestion Kinetics, and iron absorption behavior of Antarctic Krill-derived heptapeptide-iron complex.

A novel heptapeptide LVDDHFL derived from Antarctic krill was used to assemble an iron complex, of which the iron-binding mode, in vitro digestion kinetics, and iron absorption behavior were explored. Fe2+ bound to one carboxyl oxygen atom of Asp at position 4 and the imidazole group of His at position 5 on the LVDDHFL peptide at a stoichiometric ratio of 1:2, which induced the folding of LVDDHFL to form a more orderly structure. LVDDHFL-iron significantly enhanced the solubility of iron as compared to FeSO4 in the gastroduodenal tract (P < 0.05), making it up to 80.92 ± 3.02% at the end of gastroduodenal digestion. Moreover, iron complexation can enhance the digestive stability of LVDDHFL with the peptide retention rate as 62.26 ± 2.60% and approximately 27.54% of LVDDHFL were degraded to hexapeptide LVDDHF. Nevertheless, the enhancement of LVDDHF - iron on iron absorption was comparable to that of LVDDHFL - iron, but better than that of FeSO4.

Calcium Delivery Systems Assembled using Antarctic Krill Derived Heptapeptides: Exploration of the Assembly Mechanism, In Vitro Digestion Profile, and Calcium Absorption Behavior.

A novel heptapeptide QEELISK derived from Antarctic krill was used to assemble a calcium delivery system, of which the calcium binding mechanism of QEELISK, in vitro digestion kinetics, and calcium absorption behaviors were explored. QEELISK with continuous Glu possessed higher calcium binding capacity than that of QELEISK and QAALISK. Ca2+ bound to the carboxyl oxygen of Glu at position 3 of the QEELISK peptide at a stoichiometric ratio of 1:1 through charge-charge interaction; the formed QEELISK-Ca showed superior stability. Moreover, QEELISK-Ca underwent disaggregation and self-assembly during in vitro digestion reflected by visualization of calcium ions and circular dichroism spectra. QELEISK was partially stable during gastrointestinal digestion, and calcium chelation improved the digestive stability of QELEISK. In addition, a significant enhancement of calcium absorption with QELEISK-Ca occurred in the duodenum and ileum when compared to CaCl2 absorption, which indicated that QEELISK might carry calcium ions through the gastrointestinal tract.

Antarctic krill-derived peptides with consecutive Glu residues enhanced iron binding, solubility, and absorption.

Three peptides containing three glutamic acid (Glu) residues at different positions derived from Antarctic krill were obtained to investigate their iron-binding properties, digestive stability, and effectiveness on enhancing iron solubility and absorption. Results indicated that Fe2+ bound to the carbonyl, carboxyl, or hydroxyl groups of DELEDSLER, EEEFDATR, and DTDSEEEIR at stoichiometric ratios of 0.453, 0.466, and 0.490, respectively. DTDSEEEIR with three consecutive Glu in the middle of the sequence possessed higher iron-binding ability and iron release potential than EEEFDATR with three consecutive Glu in the N-terminal, and DELEDSLER with three discontinuous Glu showed the lowest values. Although EEEFDATR showed remarkably lower digestion stability than DTDSEEEIR, the effect of EEEFDATR-iron on iron solubility and absorption was comparable to that of DTDSEEEIR-iron, but better than that of DELEDSLER-iron and FeSO4. Thus, peptides with consecutive Glu have the potential as an effective iron carrier to improve iron absorption.

Can situations awaken emotions? The compilation and evaluation of the Emotional Situation Sentence System (ESSS).

We aimed to establish and evaluate a standardized emotional situation sentence system (ESSS) relevant to the lives of college students to supplement prior literature and adapt to the needs of emotional research. Two studies were designed for this research; study 1 examined the effect of words in the ESSS and study 2 involved the use of pictures. For Study 1, 778 items were selected by 607 college students and 15 experts. We then tested the scale with 80 undergraduate participants. The ESSS sentences were rated on their degree of valence, arousal, and dominance using a 9-point scale. Cronbach's α (greater than 0.986) of the overall score as well as each sub-score in the three components confirmed the scale's reliability. As seen on a scatter plot, the results suggest that negative emotions (fear, disgust, anger, sadness, anxiety) are convergent and different from the distribution of positive (happiness) and neutral emotions. Study 2 included 30 participants to compare the difference in valence and arousal between the ESSS and emotional pictures. The results indicate that the ESSS is a standardized, situational, and ecological emotional contextual text system, well-suited to invoke emotion in college students. The ESSS has significantly better arousal and potency than pictures; moreover, it can be applied to experimental studies of anxiety-related emotions. However, emotion pictures have shorter response times, and wider application ranges, and they can include more cross-cultural characteristics compared to words.

Short-Chain Poly(γ-diaminobutanoic acid), A Poly(amino acid) Produced by a Marine Bacteria Bacillus pumilus.

One marine bacteria Bacillus pumilus was isolated using allura red as ε-poly-L-lysine (ε-PL) secretion indicator. But actually the product was identified as poly-γ-L-diaminobutanoic acid (γ-PAB) by ionization-time-of-flight mass spectrometry, not coproduced with ε-PL. The polymerization degree of γ-PAB was 4-22, namely short-chain γ-PAB, compared with that in S. celluloflavus, and it exhibited stronger inhibitory activities against yeasts than long-chain γ-PAB but weaker activities against bacteria. The fermentative behavior of B. pumilus was investigated, and the γ-PAB production was 38.6 mg/L in shake flask and was enhanced to 284.2 mg/L in 5-L bioreactor by a pH control strategy. Interestingly, the suitable pH for B. pumilus to produce γ-PAB was 4.8, different from 4.0 for current Streptomyces strains, which suggests a potential new metabolic mechanism in B. pumilus as a novel γ-PAB producer. No studies on short-chain γ-PAB production in bacteria have been reported previously and we considered that this is a new discovery in the field of homopolymer research.

Efficacy of Acupuncture Treatment of Migraine Delivered by Senior or Junior Acupuncturists: Study Protocol for a Randomized Controlled Trial.

INTRODUCTION: Acupuncture is an efficacious and safe treatment choice for migraine prevention. Results from clinical trials have shown that non-specific effects play an important role in acupuncture's efficacy. To date, however, there is no evidence available quantitatively evaluating the effect of non-specific effects, such as patients' expectations and beliefs for acupuncturists, on acupuncture efficacy, necessitating further exploration. METHODS: A total of 156 patients with migraine without aura (MwoA) will be randomized to either junior or senior acupuncturist group, at a ratio of 1:1. The study will last 24 weeks, for each patient, comprising baseline, treatment, and follow-up phases lasting 4, 8, and 12 weeks, respectively. All patients will undergo 12 sections of acupuncture treatment delivered by either a junior or senior acupuncturist following the same acupuncture prescription and manipulation. The primary outcomes will be changes in the number of migraine days and frequency of attacks per 4 weeks cycle, relative to the baseline. Secondary outcomes will include severity of headache pain, quality of life, anxiety/depression levels, and use of non-steroidal anti-inflammatory drugs (NSAIDs) per 4 weeks cycle, compared to the baseline, as well as adverse events and rate of positive response to treatment. Prior to randomization of patients into junior or senior acupuncturist groups, the Acupuncture Expectations Evaluation Scale (AES) will be used to evaluate their expectations and belief with regards to acupuncture efficacy delivered by senior or junior acupuncturists. DISCUSSION: Results from this clinical randomized controlled trial will help to quantitatively evaluate the extent of the effect of acupuncture treatment delivered by a senior or junior acupuncturist (high relative to low expectations) in migraine patients. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Boards and Ethics Committees of Hospital of Chengdu University of Traditional Chinese Medicine (Approval No. 2020KL-058).

Antarctic Krill Derived Nonapeptide as an Effective Iron-Binding Ligand for Facilitating Iron Absorption via the Small Intestine.

A novel nonapeptide DTDSEEEIR identified from Antarctic krill (Euphausia superba) iron-binding peptides was used in this study to analyze its iron-binding sites and structural changes after iron coordination. The enzymatic resistance and transport of DTDSEEEIR-iron during gastrointestinal digestion and absorption as well as the relationship between the DTDSEEEIR stability and the enhancement of iron absorption were further explored. Results revealed that iron ions spontaneously bound to the carboxyl, hydroxyl, and amino groups of the DTDSEEEIR peptide, which induced the folding of DTDSEEEIR to form a more orderly structure. The DTDSEEEIR peptide remained stable to a certain extent (79.60 ± 0.19%) after gastrointestinal digestion and the coordination of iron improved the digestive stability of the DTDSEEEIR peptide (93.89 ± 1.37%). Moreover, the stability of DTDSEEEIR across intestinal epithelium had a positive effect on iron absorption, which implied that DTDSEEEIR might carry iron ions through intestinal epithelial cells.

Enhancement of ε-poly-L-lysine production in Streptomyces griseofuscus by addition of exogenous astaxanthin.

Addition of exogenous astaxanthin for improving ε-poly-L-lysine (ε-PL) production in Streptomyces griseofuscus was investigated in this study. By this unique strategy, the ε-PL production in shaker-flask fermentation was 2.48 g/L, which was 67.5% higher than the control at the addition dosage of 1.0 g/L, owing to the oxidation resistance of astaxanthin. In fed-batch fermentation, the ε-PL production reached 36.1 g/L, a 36.3% increase compared to the control. Intracellular response for oxidation in S. griseofuscus such as ROS generation and lipid peroxidation was reduced by astaxanthin addition. Illumina RNA deep sequencing (RNA-seq) technology further revealed that S. griseofuscus with astaxanthin addition showed down-regulated transcriptions of genes involved in oxidative stress. This research proved that the beneficial effect of astaxanthin addition was far better than glutathione (GSH) owing to the stronger antioxidant capacity, and provided a novel approach to regulate ε-PL synthesis.

Effect of dynamic ultra-high pressure homogenization on the structure and functional properties of whey protein.

The effects of dynamic ultra-high pressure homogenization (UHPH) on the structure and functional properties of whey protein were investigated in this study. Whey protein solution of 10 mg/mL (1% w/w) was prepared and processed by a laboratory scale high pressure homogenizer with different pressures (25, 50, 100, 150, 200, and 250 MPa) at an initial temperature of 25 °C. Then, the solution samples were evaluated in terms of secondary structure, sulfhydryl and disulfide bond contents, surface hydrophobicity, average particle size, solubility, foaming capacity, emulsifying activity, and thermal properties. It was found that the secondary structure of whey protein changed with the dynamic UHPH treatment. The interchange reaction between the disulfide bond and the sulfhydryl group was promoted and the surface hydrophobicity significantly increased. The functional properties of the whey protein accordingly changed. Specifically, after dynamic UHPH treatment, the average particle size of the whey protein and emulsion decreased while the solubility, the foaming capability and the emulsification stability increased significantly. The results also revealed that with the dynamic UHPH at 150 MPa, the best improvement was observed in the whey protein functional properties. The whey protein solubility increased from 63.15 to 71.61% and the emulsification stability improved from 195 to 467 min.

[Determination of 50 non-edible additives in health food using the QuEChERS method and liquid chromatography-tandem mass spectrometry].

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the determination of 50 non-food additives in health food. The samples were extracted with methanol and purified using the QuEChERS method. The separation was performed on an Agilent Phoroshell SB C18 column (150 mm×3.0 mm, 2.7 µm) with a mobile phase of 0.1% (v/v) formic acid aqueous solution and acetonitrile. The determination was performed by MS/MS in positive or negative electrospray ionization and multiple reaction monitoring mode. The results demonstrated that all 50 compounds could be well separated with a good linear relationship (r2>0.99). The limits of detection (LODs, S/N ≥ 3) and limits of quantification (LOQs, S/N ≥ 10) were in the range of 0.010-1 mg/kg and 0.020-2 mg/kg, respectively. The matrix effects in five kinds of typical health foods (oral liquid, tablets, ointments, pills, and capsules) were evaluated and reduced by means of matrix matching. At the spiked levels of 1 LOQ, 2 LOQ, and 10 LOQ, the recoveries of all drugs varied from 63.1% to 115.7% with relative standard deviations (RSDs) of no more than 8.9% (n=6). The method is simple, sensitive, practical, and suitable for monitoring 50 non-edible additives in health food.

Global wetlands: Potential distribution, wetland loss, and status.

Even though researchers have paid a great deal of attention to wetland loss and status, the actual extent of wetland loss on a global scale, especially the loss caused directly by human activities, and the actual extent of currently surviving wetlands remains uncertain. This paper simulated the potential distribution of global wetlands by employing a new Precipitation Topographic Wetness Index (PTWI) and global remote sensing training samples. The results show earth would have approximately 29.83millionkm2 of wetlands, if humans did not interfere with wetland ecosystems. By combining datasets related to global wetlands, we found that at least 33% of global wetlands had been lost as of 2009, including 4.58millionkm2 of non-water wetlands and 2.64millionkm2 of open water. The areal extent of wetland loss has been greatest in Asia, but Europe has experienced the most serious losses. Wetland-related datasets suffer from major inconsistencies, and estimates of the areal extent of the remaining global wetlands ranged from 1.53 to 14.86millionkm2. Therefore, although it is challenging, thematic mapping of global wetlands is necessary and urgently needed.