Update of gut gas metabolism in ulcerative colitis.

INTRODUCTION: Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED: In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION: Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.

Quercetin protects against hypertensive renal injury by attenuating apoptosis: an integrated approach using network pharmacology and RNA-Seq.

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

Assessing the Post-Activation Performance Enhancement of Upper Limbs in Basketball Athletes: A Sensor-Based Study of Rapid Stretch Compound and Blood Flow Restriction Training.

OBJECTIVE: This study introduces a novel methodology combining rapid stretch compound training with blood flow restriction (BFR) to investigate post activation performance enhancement (PAPE) in basketball players, a field that has been predominantly explored for lower limbs. We aimed to assess the efficacy of this combined approach on upper limb muscle performance in athletes. METHODS: We employed a randomized, self-controlled crossover trial with ten male basketball players. The bench press throw (BPT) served as the primary metric, with players undergoing four interventions post-baseline: (1) STR-plyometric training; (2) BFR-blood flow restriction; (3) COMB-STR integrated with BFR; and (4) CON-control. Innovatively, we utilized an intelligent tracking sensor to precisely measure peak power (PP), peak velocity (PV), mean power (MP), and mean velocity (MV) at 4, 8, and 12 min post-intervention, providing a detailed temporal analysis of PAPE. RESULTS: The COMB intervention demonstrated superior PAPE effects at 4 min, significantly outperforming STR and BFR alone and the control group across all measured indices (p < 0.05). Notably, the COMB group maintained these improvements for PV, PP, and H up to 12 min post-intervention, suggesting a prolonged effect. CONCLUSION: (1) The COMB stimulation has been shown to successfully induce PAPE more effectively than STR and BFR modality alone. (2) It appears that the optimal effects of PAPE are achieved within 4 min of exercising under this COMB. By the 12 min mark, only the COMB group continued to show significant improvements in PV, PP, and H compared to both the baseline and the CON group, while the effects in the STR and BFR groups further diminished. This suggests that although the PAPE effect is maintained over time, its optimal performance may peak at the 4 min mark and then gradually weaken as time progresses.

Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Individualized lipid profile in urine-derived extracellular vesicles from clinical patients with Mycobacterium tuberculosis infections.

Background: Lipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection. Methods: Urine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package. Results: Overall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression. Conclusion: This study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB.

Assessing immune hepatotoxicity of troglitazone with a versatile liver-immune-microphysiological-system.

Drug-induced liver injury is a prevalent adverse event associated with pharmaceutical agents. More significantly, there are certain drugs that present severe hepatotoxicity only during the clinical phase, consequently leading to the termination of drug development during clinical trials or the withdrawal from the market after approval. The establishment of an evaluation model that can sensitively manifest such hepatotoxicity has always been a challenging aspect in drug development. In this study, we build a liver-immune-microphysiological-system (LIMPS) to fully demonstrate the liver injury triggered by troglitazone (TGZ), a drug that was withdrawn from the market due to hepatotoxicity. Leveraging the capabilities of organ-on-chip technology allows for the dynamic modulation of cellular immune milieu, as well as the synergistic effects between drugs, hepatocytes and multiple immune cells. Through the LIMPS, we discovered that 1) TGZ can promote neutrophils to adhered hepatocytes, 2) the presence of TGZ enhances the crosstalk between macrophages and neutrophils, 3) the induction of damage in hepatocytes by TGZ at clinically relevant blood concentrations not observed in other in vitro experiments, 4) no hepatotoxicity was observed in LIMPS when exposed to rosiglitazone and pioglitazone, structurally similar analogs of TGZ, even at the higher multiples of blood drug concentration levels. As an immune-mediated liver toxicity assessment method, LIMPS is simple to operate and can be used to test multiple drug candidates to detect whether they will cause severe liver toxicity in clinical settings as early as possible.

Influence of the non-equal aligned nozzles for fuel injection inside the supersonic combustion chamber.

The importance of fuel mixing for the progress of the scramjet engine is indisputable. The present article shows the importance of the non-equal multi-injector system for effective fuel distribution and flame holding inside the combustion segment of a scramjet engine. The supersonic air and fuel jet flow in the non-equal nozzle arrangement is simulated via computational fluid dynamic technique. Two injector types of circular and rectangular nozzle have been analyzed to attain flow characteristics of hydrogen jets at supersonic cross flow. Mach contour is also analyzed for these jet arrangements to show the interface of the jet in the non-equal jet arrangement. Besides, addition of internal air jet is also simulated and evaluated in this research. Our investigation shows that the diffusion height of the fuel jet is higher when a rectangular non-equal nozzle is applied. The circular nozzle is more active in the spreading of the fuel in the combustor and the use of an internal air jet effectively increases fuel in a combustor of the scramjet.

Tailoring Cu-Based Electrocatalysts for Enhanced Electrochemical CO2 Reduction to Alcohols: Structure-Selectivity Relationship.

The use of CO2 as a feedstock for the production of carbon-based fuels and value-added chemicals offers a promising route toward carbon neutrality. In this study, two Cu-based electrocatalysts, namely, Cu24/N-C and Cu2/N-C, are successfully prepared by thermal treatment of Cu24 metal-organic polyhedron-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocrystals (Cu24/ZIF-8) and Cu2 dinuclear compound-loaded ZIF-8 nanocrystals (Cu2/ZIF-8), respectively. Extensive structural and compositional analyses were conducted to confirm the formation of Cu nanocluster-loaded N-doped porous carbon supports in both Cu24/N-C and Cu2/N-C and Cu nanoparticles encapsulated by graphitic carbons in Cu2/N-C as well. These two Cu-based electrocatalysts exhibited different behaviors in the electrochemical CO2 reduction reaction (CO2RR). The Cu24/N-C electrocatalyst showed high selectivity for CO production, while Cu2/N-C showed a preference for alcohol generation. The excellent stability of Cu2/N-C over a 30 h continuous electrochemical reduction further highlights its potential for practical applications. The difference in electrocatalytic performance observed in the two catalysts for CO2RR was attributed to distinct catalytic sites associated with Cu nanoclusters and nanoparticles. This research reveals the significance of their structures and compositions for the development of highly selective electrocatalysts for CO2 reduction.

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway.

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis.

BACKGROUND: Store-operated Ca2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP. METHOD: Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca2+ signals were measured by time-lapse confocal microscope imaging, with a Ca2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured. RESULT: Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1ß were higher in Orai1ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor. CONCLUSION: Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.

THSG alleviates cerebral ischemia/reperfusion injury via the GluN2B-CaMKII-ERK1/2 pathway.

BACKGROUND: The potential therapeutic targeting of PINK1-PARK2-mediated mitophagy against cerebral ischemia/reperfusion (CI/R) injury involves the pathophysiological processes of neurovascular unit (NVU) and is closely associated with N-methyl-D-aspartate receptors (NMDARs) commonly expressed in NVU. 2,3,5,4'-Tetrahydroxy-stilbene-2-O-ß-D-glucoside (THSG), a compound derived from the traditional Chinese medicine Polygonum multiflorum Thunb., has demonstrated notable neuroprotective properties against CI/R injury. However, it remains unclear whether THSG exerts its protective effects through GluN2B related PINK1/ PARK2 pathway. PURPOSE: This study aims to explore the pharmacological effects of THSG on alleviating CI/R injury via the GluN2B-CaMKII-ERK1/2 pathway. METHODS: THSG neuroprotection against CI/R injury was studied in transient middle cerebral artery occlusion/reversion (tMCAO/R) model rats and in oxygen and glucose deprivation/ reoxygenation (OGD/R) induced neurons. PINK1-PARK2-mediated mitophagy involvement in the protective effect of THSG was investigated in tMCAO/R rats and OGD/R-induced neurons via THSG and 3-methyladenine (3-MA) treatment. Furthermore, the beneficial role of GluN2B in reperfusion and its contribution to the THSG effect via CaMKII-ERK1/2 and PINK1-PARK2-mediated mitophagy was explored using the GluN2B-selective antagonist Ro 25-6981 both in vivo and in vitro. Finally, the interaction between THSG and GluN2B was evaluated using molecular docking. RESULTS: THSG significantly reduced infarct volume, neurological deficits, penumbral neuron structure, and functional damage, upregulated the inhibitory apoptotic marker Bcl-2, and suppressed the increase of pro-apoptotic proteins including cleaved caspase-3 and Bax in tMCAO/R rats. THSG (1 µM) markedly improved the neuronal survival under OGD/R conditions. Furthermore, THSG promoted PINK1 and PARK2 expression and increased mitophagosome numbers and LC3-II-LC3-I ratio both in vivo and in vitro. The effects of THSG were considerably abrogated by the mitophagy inhibitor 3-MA in OGD/R-induced neurons. Inhibiting GluN2B profoundly decreased mitophagosome numbers and OGD/R-induced neuronal viability. Specifically, inhibiting GluN2B abolished the protection of THSG against CI/R injury and reversed the upregulation of PINK1-PARK2-mediated mitophagy by THSG. Inhibiting GluN2B eliminated THSG upregulation of ERK1/2 and CaMKII phosphorylation. The molecular docking analysis results demonstrated that THSG bound to GluN2B (binding energy: -5.2 ± 0.11 kcal/mol). CONCLUSIONS: This study validates the premise that THSG alleviates CI/R injury by promoting GluN2B expression, activating CaMKII and ERK1/2, and subsequently enhancing PINK1-PARK2-mediated mitophagy. This work enlightens the potential of THSG as a promising candidate for novel therapeutic strategies for treating ischemic stroke.

Cu-nanocluster-loaded N-doped porous graphitic carbon for electrochemical CO2 reduction towards syngas generation.

In this study, a novel electrocatalyst, namely Cu/N-pg-C derived from Cu-doped ZIF-8, was investigated for making syngas products with various H2/CO ratios. Different ratios of the electrocatalytic syngas products CO and H2 could be selected by adjusting the applied potential and hence tuning the transfer of electrons from N-doped graphitic carbon to the well-dispersed Cu nanoclusters.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells.

Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1-Palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), an oxidized phospholipid, is found in atherosclerotic plaques and has been shown to induce oxidative stress. However, the effects of POVPC on osteogenic differentiation and calcification of VSMCs have yet to be studied. In the present study, we investigated the role of POVPC in vascular calcification using in vitro and ex vivo models. POVPC increased mineralization of VSMCs and arterial rings, as shown by alizarin red staining. In addition, POVPC treatment increased expression of osteogenic markers Runx2 and BMP2, indicating that POVPC promotes osteogenic transition of VSMCs. Moreover, POVPC increased oxidative stress and impaired mitochondria function of VSMCs, as shown by increased ROS levels, impairment of mitochondrial membrane potential, and decreased ATP levels. Notably, ferroptosis triggered by POVPC was confirmed by increased levels of intracellular ROS, lipid ROS, and MDA, which were decreased by ferrostatin-1, a ferroptosis inhibitor. Furthermore, ferrostatin-1 attenuated POVPC-induced calcification of VSMCs. Taken together, our study for the first time demonstrates that POVPC promotes vascular calcification via activation of VSMC ferroptosis. Reducing the levels of POVPC or inhibiting ferroptosis might provide a novel strategy to treat vascular calcification.

Development of a CD163-Targeted PET Radiotracer That Images Resident Macrophages in Atherosclerosis.

Tissue-resident macrophages are complementary to proinflammatory macrophages to promote the progression of atherosclerosis. The noninvasive detection of their presence and dynamic variation will be important to the understanding of their role in the pathogenesis of atherosclerosis. The goal of this study was to develop a targeted PET radiotracer for imaging CD163-positive (CD163+) macrophages in multiple mouse atherosclerosis models and assess the potential of CD163 as a biomarker for atherosclerosis in humans. Methods: CD163-binding peptide was identified using phage display and conjugated with a NODAGA chelator for 64Cu radiolabeling ([64Cu]Cu-ICT-01). CD163-overexpressing U87 cells were used to measure the binding affinity of [64Cu]Cu-ICT-01. Biodistribution studies were performed on wild-type C57BL/6 mice at multiple time points after tail vein injection. The sensitivity and specificity of [64Cu]Cu-ICT-01 in imaging CD163+ macrophages upregulated on the surface of atherosclerotic plaques were assessed in multiple mouse atherosclerosis models. Immunostaining, flow cytometry, and single-cell RNA sequencing were performed to characterize the expression of CD163 on tissue-resident macrophages. Human carotid atherosclerotic plaques were used to measure the expression of CD163+ resident macrophages and test the binding specificity of [64Cu]Cu-ICT-01. Results: [64Cu]Cu-ICT-01 showed high binding affinity to U87 cells. The biodistribution study showed rapid blood and renal clearance with low retention in all major organs at 1, 2, and 4 h after injection. In an ApoE-/- mouse model, [64Cu]Cu-ICT-01 demonstrated sensitive and specific detection of CD163+ macrophages and capability for tracking the progression of atherosclerotic lesions; these findings were further confirmed in Ldlr-/- and PCSK9 mouse models. Immunostaining showed elevated expression of CD163+ macrophages across the plaques. Flow cytometry and single-cell RNA sequencing confirmed the specific expression of CD163 on tissue-resident macrophages. Human tissue characterization demonstrated high expression of CD163+ macrophages on atherosclerotic lesions, and ex vivo autoradiography revealed specific binding of [64Cu]Cu-ICT-01 to human CD163. Conclusion: This work reported the development of a PET radiotracer binding CD163+ macrophages. The elevated expression of CD163+ resident macrophages on human plaques indicated the potential of CD163 as a biomarker for vulnerable plaques. The sensitivity and specificity of [64Cu]Cu-ICT-01 in imaging CD163+ macrophages warrant further investigation in translational settings.

Research on Dynamic Modeling Method and Flying Gait Characteristics of Quadruped Robots with Flexible Spines.

In recent years, both domestic and international research on quadruped robots has advanced towards high dynamics and agility, with a focus on high-speed locomotion as a representative motion in high-dynamic activities. Quadruped animals like cheetahs exhibit high-speed running capabilities, attributed to the indispensable role played by their flexible spines during the flight phase motion. This paper establishes dynamic models of flexible spinal quadruped robots with different degrees of simplification, providing a parameterized description of the flight phase motion for both rigid-trunk and flexible-spine quadruped robots. By setting different initial values for the spine joint and calculating the flight phase results for both types of robots at various initial velocities, the study compares and analyzes the impact of a flexible spine on the flight phase motion of quadruped robots. Through comparative experiments, the research aims to validate the influence of a flexible spine during the flight phase motion, providing insights into how spine flexibility affects the flight phase motion of quadruped robots.

Development of a CCR2 targeted 18F-labeled radiotracer for atherosclerosis imaging with PET.

Atherosclerosis is a chronic inflammatory disease and the leading cause of morbidity and mortality worldwide. CC motif chemokine ligand 2 and its corresponding cognate receptor 2 (CCL2/CCR2) signaling has been implicated in regulating monocyte recruitment and macrophage polarization during inflammatory responses that plays a pivotal role in atherosclerosis initiation and progression. In this study, we report the design and synthesis of a novel 18F radiolabeled small molecule radiotracer for CCR2-targeted positron emission tomography (PET) imaging in atherosclerosis. The binding affinity of this radiotracer to CCR2 was evaluated via in vitro binding assay using CCR2+ membrane and cells. Ex vivo biodistribution was carried out in wild type mice to assess radiotracer pharmacokinetics. CCR2 targeted PET imaging of plaques was performed in two murine atherosclerotic models. The sensitive detection of atherosclerotic lesions highlighted the potential of this radiotracer for CCR2 targeted PET and warranted further optimization.

Effects of Dietary Alfalfa Meal Supplementation on the Growth Performance, Nutrient Apparent Digestibility, Serum Parameters, and Intestinal Microbiota of Raccoon Dogs (Nyctereutes procyonoides).

The raccoon dog (Nyctereutes procyonoides) is a typical omnivore possessing wide dietary adaptability and tolerance to rough feeding, which may be attributed to its intestinal microbiota. The study aimed to investigate the effect of dietary alfalfa meal levels on the growth performance, nutrient apparent digestibility, serum parameters, and intestinal microbiota of raccoon dogs. Sixty raccoon dogs were randomly divided into four dietary treatments containing 0% (AM0), 5% (AM5), 10% (AM10), and 15% (AM15) alfalfa meal for a 60-day experiment. The results showed that compared to raccoon dogs fed the AM0 diet, those fed the AM5 and AM10 diets had no significant difference in growth performance, while those fed the AM15 diet experienced a significant decrease. Raccoon dogs fed the AM5 diet had no significant effect on the nutrient apparent digestibility. Dietary supplementation with alfalfa meal significantly decreased serum urea levels and increased the antioxidant capacity of raccoon dogs. The intestinal microbiome analysis showed that the richness and diversity of colonic microbiota significantly increased in the AM15 group. With the increase in dietary alfalfa meal levels, the relative abundance of fiber-degrading bacteria in the colon of raccoon dogs, such as Treponema, Phascolarctobacterium, and Christensenellaceae R-7 group, increased. However, the relative abundance of pathogenic bacteria, including Anaerobiospirillum, decreased. In conclusion, the inclusion of 5% alfalfa meal in the raccoon dogs' diet had no effect on growth performance, but it exhibited the potential to improve serum antioxidant capacity and intestinal microbiota. This indicates that raccoon dogs have a certain tolerance to the addition of alfalfa meal in their diet.