Transfer learning for clustering single-cell RNA-seq data crossing-species and batch, case on uterine fibroids.

Due to the high dimensionality and sparsity of the gene expression matrix in single-cell RNA-sequencing (scRNA-seq) data, coupled with significant noise generated by shallow sequencing, it poses a great challenge for cell clustering methods. While numerous computational methods have been proposed, the majority of existing approaches center on processing the target dataset itself. This approach disregards the wealth of knowledge present within other species and batches of scRNA-seq data. In light of this, our paper proposes a novel method named graph-based deep embedding clustering (GDEC) that leverages transfer learning across species and batches. GDEC integrates graph convolutional networks, effectively overcoming the challenges posed by sparse gene expression matrices. Additionally, the incorporation of DEC in GDEC enables the partitioning of cell clusters within a lower-dimensional space, thereby mitigating the adverse effects of noise on clustering outcomes. GDEC constructs a model based on existing scRNA-seq datasets and then applying transfer learning techniques to fine-tune the model using a limited amount of prior knowledge gleaned from the target dataset. This empowers GDEC to adeptly cluster scRNA-seq data cross different species and batches. Through cross-species and cross-batch clustering experiments, we conducted a comparative analysis between GDEC and conventional packages. Furthermore, we implemented GDEC on the scRNA-seq data of uterine fibroids. Compared results obtained from the Seurat package, GDEC unveiled a novel cell type (epithelial cells) and identified a notable number of new pathways among various cell types, thus underscoring the enhanced analytical capabilities of GDEC. Availability and implementation: https://github.com/YuzhiSun/GDEC/tree/main.

Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Metal Variance in Multivariate Metal-Organic Frameworks for Boosting Catalytic Conversion of CO2.

Developing efficient, low-cost, MOF catalysts for CO2 conversion at low CO2 concentrations under mild conditions is particularly interesting but remains highly challenging. Herein, we prepared an isostructural series of two-dimensional (2D) multivariate metal-organic frameworks (MTV-MOFs) containing copper- and/or silver-based cyclic trinuclear complexes (Cu-CTC and Ag-CTC). These MTV-MOFs can be used as efficient and reusable heterogeneous catalysts for the cyclization of propargylamine with CO2. The catalytic performance of these MTV-MOFs can be engineered by fine-tuning the Ag/Cu ratio in the framework. Interestingly, the induction of 10% Ag remarkably improved the catalytic efficiency with a turnover frequency (TOF) of 243 h-1, which is 20-fold higher than that of 100% Cu-based MOF (i.e., TOF = 10.8 h-1). More impressively, such a bimetallic MOF still exhibited high catalytic activity even for simulated flue gas with 10% CO2 concentration. Furthermore, the reaction mechanism has been examined through the employment of NMR monitoring experiments and DFT calculations.

Multifunctional Metal-Organic Frameworks as Catalysts for Tandem Reactions.

Owing to well-defined structure as well as easy synthesis and modification, metal-organic frameworks (MOFs) have emerged as promising catalysts for tandem reactions. In this article, we aim to summarize the development of multifunctional MOFs, including mixed metal MOFs, MOFs that are synergistically catalyzed by metal nodes and organic linkers, MOFs loaded with metal nanoparticles, etc, as heterogenous catalysts for tandem reactions over the past five years. This concept briefly discusses on present challenges, future trends, and prospects of multifunctional MOFs catalysts in tandem reactions.

Systematical Investigation on Anti-Fatigue Function and Underlying Mechanism of High Fischer Ratio Oligopeptides from Antarctic Krill on Exercise-Induced Fatigue in Mice.

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body's energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-α proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods.

New polyketides from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2.

One new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 µg/ml.

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs (II): Protective Function on UVB-Irradiated HaCaT Cells through Antioxidant and Anti-Apoptotic Mechanisms.

The aim of this study was to investigate the protective function and mechanism of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from skipjack tuna cardiac arterial bulbs on skin photoaging using UVB-irradiated HaCaT cell model. The present results indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) had significant cytoprotective effect on UVB-irradiated HaCaT cells (p < 0.001). Hoechst 33342 staining showed that apoptosis of UV-irradiated HaCaT cells could be significantly reduced by the treatment of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM); JC-1 staining showed that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could protect HaCaT cells from apoptosis by restoring mitochondrial membrane potential (MMP); Furthermore, TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could significantly down-regulate the ratio of Bax/Bcl-2 and reduce the expression level of the apoptosis-executing protein Caspase-3 by decreasing the expression of protein Caspase-8 and Caspase-9 (p < 0.05). The action mechanism indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could up-regulate the expression levels of Nrf2, NQO1 and HO-1 (p < 0.05), which further increased the activity of downstream proteases (SOD, CAT and GSH-Px), and scavenged reactive oxygen species (ROS) and decreased the intracellular levels of malondialdehyde (MDA). In addition, molecular docking indicated that TCP3 (PKK) and TCP6 (YEGGD) could competitively inhibit the Nrf2 binding site because they can occupy the connection site of Nrf2 by binding to the Kelch domain of Keap1 protein. TCP9 (GPGLM) was inferred to be non-competitive inhibition because it could not bind to the active site of the Kelch domain of Keap1 protein. In summary, the antioxidant peptides TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from cardiac arterial bulbs of skipjack tuna can effectively protect HaCaT cells from UVB-irradiated damage and can be used in the development of healthy and cosmetic products to treat diseases caused by UV radiation.

Novel Ca-Chelating Peptides from Protein Hydrolysate of Antarctic Krill (Euphausia superba): Preparation, Characterization, and Calcium Absorption Efficiency in Caco-2 Cell Monolayer Model.

Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.

Eighteen Novel Bioactive Peptides from Monkfish (Lophius litulon) Swim Bladders: Production, Identification, Antioxidant Activity, and Stability.

In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (Lophius litulon) processing byproducts, and the hydrolysis conditions of papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme dose 2.5% and time 5 h using single-factor and orthogonal experiments. Eighteen peptides were purified from the swim bladder hydrolysate of monkfish by ultrafiltration and gel permeation chromatography methods and identified as YDYD, QDYD, AGPAS, GPGPHGPSGP, GPK, HRE, GRW, ARW, GPTE, DDGGK, IGPAS, AKPAT, YPAGP, DPT, FPGPT, GPGPT, GPT and DPAGP, respectively. Among eighteen peptides, GRW and ARW showed significant DPPH· scavenging activities with EC50 values of 1.053 ± 0.003 and 0.773 ± 0.003 mg/mL, respectively; YDYD, QDYD, GRW, ARW and YPAGP revealed significantly HO· scavenging activities with EC50 values of 0.150 ± 0.060, 0.177 ± 0.035, 0.201 ± 0.013, 0.183 ± 0.0016 and 0.190 ± 0.010 mg/mL, respectively; YDYD, QDYD, ARW, DDGGK and YPAGP have significantly O2-· scavenging capability with EC50 values of 0.126 ± 0.0005, 0.112 ± 0.0028, 0.127 ± 0.0002, 0.128 ± 0.0018 and 0.107 ± 0.0002 mg/mL, respectively; and YDYD, QDYD and YPAGP showed strong ABTS+· scavenging ability with EC50 values of 3.197 ± 0.036, 2.337 ± 0.016 and 3.839 ± 0.102 mg/mL, respectively. YDYD, ARW and DDGGK displayed the remarkable ability of lipid peroxidation inhibition and Ferric-reducing antioxidant properties. Moreover, YDYD and ARW can protect Plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, eighteen isolated peptides had high stability under temperatures ranging from 25-100 °C; YDYD, QDYD, GRW and ARW were more sensitive to alkali treatment, but DDGGK and YPAGP were more sensitive to acid treatment; and YDYD showed strong stability treated with simulated GI digestion. Therefore, the prepared antioxidant peptides, especially YDYD, QDYD, GRW, ARW, DDGGK and YPAGP from monkfish swim bladders could serve as functional components applied in health-promoting products because of their high-antioxidant functions.

Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway.

In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the expression of phospho-AMP-activated protein kinase (p-AMPK) proteins to inhibit the expression of the sterol regulatory element binding protein-1c (SREBP-1c) proteins on increasing lipid synthesis and up-regulating the expression of the PPAP-α and CPT-1 proteins on promoting the ß-oxidation of fatty acids. Moreover, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) can significantly inhibit reactive oxygen species' (ROS) production, promote the activities of intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; and catalase, CAT) and bring down the content of malondialdehyde (MDA) derived from lipid peroxidation. Further investigations revealed that the regulation of these five oligopeptides on oxidative stress was achieved through activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to raise the expression levels of the heme oxygenase 1 (HO-1) protein and downstream antioxidant proteases. Therefore, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) could serve as candidate ingredients to develop functional products for treating NAFLD.

An Atomically Precise Pyrazolate-Protected Copper Nanocluster Exhibiting Exceptional Stability and Catalytic Activity.

The synthesis of atomically precise copper nanoclusters (Cu-NCs) with high chemical stability is a prerequisite for practical applications, yet still remains a long-standing challenge. Herein, we have prepared a pyrazolate-protected Cu-NC (Cu8), which exhibited exceptional chemical stability either in solid-state or in solution. The crystals of Cu8 are still suitable for single crystal X-ray diffraction analysis even after being treated with boiling water, 8 wt % H2 O2 , high concentrated acid (1 M HCl) or saturated base (≈20 M KOH), respectively. More importantly, the structure of Cu8 in solution also remained intact toward oxygen, organic acid (100 eq. HOAc) or base (400 eq. dibutylamine) confirmed by 1 H NMR and UV/Vis analysis. Taking advantage of high alkali-resistant, Cu8 illustrates excellent catalytic activity for the synthesis of indolizines, and it can be reused for at least 10 cycles without losing catalytic performance.

A Photosensitizing Metal-Organic Framework as a Tandem Reaction Catalyst for Primary Alcohols from Terminal Alkenes and Alkynes.

Owing to the wide and growing demand for primary alcohols, the development of efficient catalysts with high regioselectivity remains a worthwhile pursuit. However, according to Markovnikov's rule, it is a challenge to obtain primary alcohols with high yields and regioselectivity from terminal alkenes or alkynes. Herein, we report the synthesis of a photosensitizing two-dimensional (2D) metal-organic framework (MOF) from cyclic trinuclear copper(I) units (Cu-CTUs) and a boron dipyrro-methene (Bodipy) ligand. The MOF features broadband light absorption, excellent photoinduced charge separation efficiency, and photochemical properties. By integrating the copper-catalyzed hydroboration and photocatalyzed aerobic oxidation, it can catalyze terminal alkenes and alkynes to produce primary alcohols via a one-pot tandem reaction with excellent regioselectivity, good overall yields in two-step reactions (up to 85 %), broad substrate compatibility (32 examples) and good reusability under mild conditions.

The combination of arterial lactate level with GCS-pupils score to evaluate short term prognosis in traumatic brain injury: a retrospective study.

BACKGROUND: The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI). METHODS: A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05. RESULTS: A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570-0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone. CONCLUSIONS: The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.

Iodine-catalyzed oxidative annulation: facile synthesis of pyrazolooxepinopyrazolones via methyl azaarene sp3 C-H functionalization.

An iodine-catalyzed methyl azaarene sp3 C-H functionalization has been developed for the synthesis of a seven-membered O-heterocyclic architecture containing three different heterocyclic aromatic hydrocarbons. This method can be applied to a wide range of substituted methyl azaarenes and diverse 2,4-dihydro-3H-pyrazol-3-ones, and brings about the efficient preparation of 2,9-dihydrooxepino[2,3-c:6,5-c']dipyrazol-3(7H)-ones in high yields with the merits of low catalyst loading, good functional group tolerance and metal-free conditions.

Exercise-induced myocardial ischemia presenting as exercise intolerance after carbon monoxide intoxication and smoke inhalation Injury: case report.

BACKGROUND: Carbon monoxide intoxication and smoke inhalation injury can lead to severe disorders, and the current literature has elaborated on the importance of major cardiopulmonary impairment. Exercise intolerance has seldom been discussed, particular in patient with low cardiovascular risk. CASE PRESENTATION: Two young male fire survivors who presented with exercise intolerance after CO intoxication and smoke inhalation injury. Both received bronchodilator and glucocorticoid therapy, high-flow oxygen therapy, and hyperbaric oxygen therapy for airway edema and CO intoxication during acute care. Serum carboxyhemoglobin levels improved after treatment (8.2-3.9% in Case A and 14.8-0.8% in Case B). However, subjective exercise intolerance was noted after discharge. Cardiopulmonary exercise testing revealed exercise-induced myocardial ischemia during peak exercise (significant ST-segment depression on exercise electrocardiogram). They were instructed to exercise with precaution by setting the intensity threshold according to the ischemic threshold. Their symptoms improved, and no cardiopulmonary events were reported in the 6-month follow-up. CONCLUSION: The present case report raised the attention that exercise intolerance after carbon monoxide intoxication and smoke inhalation injury in low cardiovascular risk population may be underestimated. Cardiopulmonary exercise testing help physician to discover exercise-induced myocardial ischemia and set up the cardiac rehabilitation program accordingly.

Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis.

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K (1-11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1-11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of the NF-κB and MAPK signaling pathways.

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.

Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation.

Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2. Objectives: This study aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiological mechanisms. Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation + FiCO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with Vt 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury. Measurements and Main Results: Histological, physiological, and quantitative computed tomography scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics compared with the ligation + FiCO2 5% group. In the ligation group, the right lung received a larger fraction of Vt and inflammation was more represented, whereas CO2 dampened both processes. Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and antiinflammatory effects.

Novel Antioxidant Collagen Peptides of Siberian Sturgeon (Acipenserbaerii) Cartilages: The Preparation, Characterization, and Cytoprotection of H2O2-Damaged Human Umbilical Vein Endothelial Cells (HUVECs).

For making full use of aquatic by-products to produce high value-added products, Siberian sturgeon (Acipenser baerii) cartilages were degreased, mineralized, and separately hydrolyzed by five kinds of proteases. The collagen hydrolysate (SCH) generated by Alcalase showed the strongest 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·) and hydroxide radical (HO·) scavenging activity. Subsequently, thirteen antioxidant peptides (SCP1-SCP3) were isolated from SCH, and they were identified as GPTGED, GEPGEQ, GPEGPAG, VPPQD, GLEDHA, GDRGAEG, PRGFRGPV, GEYGFE, GFIGFNG, PSVSLT, IELFPGLP, LRGEAGL, and RGEPGL with molecular weights of 574.55, 615.60, 583.60, 554.60, 640.64, 660.64, 885.04, 700.70, 710.79, 602.67, 942.12, 714.82, and 627.70 Da, respectively. GEYGFE, PSVSLT, and IELFPGLP showed the highest scavenging activity on DPPH· (EC50: 1.27, 1.05, and 1.38 mg/mL, respectively) and HO· (EC50: 1.16, 0.97, and 1.63 mg/mL, respectively), inhibiting capability of lipid peroxidation, and protective functions on H2O2-damaged plasmid DNA. More importantly, GEYGFE, PSVSLT, and IELFPGLP displayed significant cytoprotection on HUVECs against H2O2 injury by regulating the endogenous antioxidant enzymes of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the contents of reactive oxygen species (ROS) and malondialdehyde (MDA). Therefore, the research provided better technical assistance for a higher-value utilization of Siberian sturgeon cartilages and the thirteen isolated peptides-especially GEYGFE, PSVSLT, and IELFPGLP-which may serve as antioxidant additives for generating health-prone products to treat chronic diseases caused by oxidative stress.

Bioactive Peptides from Skipjack Tuna Cardiac Arterial Bulbs: Preparation, Identification, Antioxidant Activity, and Stability against Thermal, pH, and Simulated Gastrointestinal Digestion Treatments.

Cardiac arterial bulbs of Skipjack tuna (Katsuwonus pelamis) are rich in elastin, and its hydrolysates are high quality raw materials for daily cosmetics. In order to effectively utilizing Skipjack tuna processing byproducts-cardiac arterial bulbs and to prepare peptides with high antioxidant activity, pepsin was selected from six proteases for hydrolyzing proteins, and the best hydrolysis conditions of pepsin were optimized. Using ultrafiltration and chromatographic methods, eleven antioxidant peptides were purified from protein hydrolysate of tuna cardiac arterial bulbs. Four tripeptides (QGD, PKK, GPQ and GLN) were identified as well as seven pentapeptides (GEQSN, GEEGD, YEGGD, GEGER, GEGQR, GPGLM and GDRGD). Three out of them, namely the tripeptide PKK and the pentapeptides YEGGD and GPGLM exhibited the highest radical scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide anion assays. They also showed to protect plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, they exhibited high stability under temperature ranged from 20-100 °C, pH values ranged from 3-11, and they simulated gastrointestinal digestion for 240 min. These results suggest that the prepared eleven antioxidant peptides from cardiac arterial bulbs, especially the three peptides PKK, YEGGD, and GPGLM, could serve as promising candidates in health-promoting products due to their high antioxidant activity and their stability.