Ghrelin may protect against vascular endothelial injury in Acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway.

Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment.

Establishment and Diagnostic Value of an Early Prediction Model for Acute Pancreatitis Complicated With Acute Kidney Injury.

OBJECTIVES: To establish an early prediction model for acute pancreatitis (AP) complicated with acute kidney injury (AKI) and evaluate its diagnostic value. METHOD: AP patients were recruited from the Emergency Department at Peking University People's Hospital in 2021 and stratified into AKI and control (no AKI) groups. Their clinical data were analyzed. The risk for AKI development was determined using logistic analyses to establish a risk prediction model, whose diagnostic value was analyzed using a receiver operating characteristic curve. RESULTS: There was no significant difference in the basic renal function between the AKI (n = 79) and control (n = 179) groups. The increased triglyceride glucose index (odds ratio [OR], 2.613; 95% confidence interval [CI], 1.324-5.158; P = 0.006), age (OR, 1.076; 95% CI, 1.016-1.140; P = 0.013), and procalcitonin (OR, 1.377; 95% CI, 1.096-1.730, P = 0.006) were associated with AKI development. A model was established for prediction of AKI (sensitivity 79.75%, specificity 96.65%). The area under the receiver operating characteristic curve was 0.856 which was superior to the Ranson, Bedside Index for Severity in AP, and Acute Physiology and Chronic Health Evaluation II scores (0.856 vs 0.691 vs 0.745 vs 0.705). CONCLUSIONS: The prediction model based on age, triglyceride glucose, and procalcitonin is valuable for the prediction of AP-related AKI.

Prediction of disease progression in individuals with subjective cognitive decline using brain network analysis.

OBJECTIVE: The objective of this study is to explore potential differences in brain functional networks at baseline between individuals with progressive subjective cognitive decline (P-SCD) and stable subjective cognitive decline (S-SCD), as well as to identify potential indicators that can effectively distinguish between P-SCD and S-SCD. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) database was utilized to enroll SCD individuals with a follow-up period of over 3 years. This study included 39 individuals with S-SCD, 15 individuals with P-SCD, and 45 cognitively normal (CN) individuals. Brain functional networks were constructed based on the AAL template, and graph theory analysis was performed to determine the topological properties. RESULTS: For global metric, the S-SCD group exhibited stronger small-worldness with reduced connectivity among nearby nodes and accelerated compensatory information transfer capacity. For nodal efficiency, the S-SCD group showed increased connectivity in bilateral posterior cingulate gyri (PCG). However, for nodal local efficiency, the P-SCD group exhibited significantly reduced connectivity in the right cerebellar Crus I compared with the S-SCD group. CONCLUSION: There are differences in brain functional networks at baseline between P-SCD and S-SCD groups. Furthermore, the right cerebellar Crus I region may be a potentially useful brain area to distinguish between P-SCD and S-SCD.

White matter substrates underlying morphological awareness deficit in Chinese children with developmental dyslexia.

BACKGROUND: Morphological awareness (MA) deficit is strongly associated with Chinese developmental dyslexia (DD). However, little is known about the white matter substrates underlying the MA deficit in Chinese children with DD. METHODS: In the current study, 34 Chinese children with DD and 42 typical developmental (TD) children were recruited to complete a diffusion magnetic resonance imaging scan and cognitive tests for MA. We conducted linear regression to test the correlation between MA and DTI metrics, the structural abnormalities of the tracts related to MA, and the interaction effect of DTI metrics by group on MA. RESULTS: First, MA was significant related to the right inferior occipito-frontal fascicle (IFO) and inferior longitudinal fsciculus (ILF), the bilateral thalamo-occipital (T_OCC) and the left arcuate fasciculus (AF); second, compared to TD children, Chinese children with DD had lower axial diffusivity (AD) in the right IFO and T_OCC; third, there were significant interactions between metrics (fractional anisotropy (FA) and radial diffusivity (RD)) of the right IFO and MA in groups. The FA and RD of the right IFO were significantly associated with MA in children with DD but not in TD children. CONCLUSION: In conclusion, compared to TD children, Chinese children with DD had axonal degeneration not only in the ventral tract (the right IFO) but also the visuospatial tract (the right T_OCC) which were associated with their MA deficit. And Chinese MA involved not only the ventral tracts, but also the visuospatial pathway and dorsal tracts.

Seasonal-Spatial Distribution Variations and Predictions of Loliolus beka and Loliolus uyii in the East China Sea Region: Implications from Climate Change Scenarios.

Global climate change profoundly impacts the East China Sea ecosystem and poses a major challenge to fishery management in this region. In addition, closely related species with low catches are often not distinguished in fishery production and relevant data are commonly merged in statistics and fishing logbooks, making it challenging to accurately predict their habitat distribution range. Here, merged fisheries-independent data of the closely related squid Loliolus beka (Sasaki, 1929) and Loliolus uyii (Wakiya and Ishikawa, 1921) were used to explore the construction and prediction performance of species distribution models. Data in 2018 to 2019 from the southern Yellow and East China Seas were used to identify the seasonal-spatial distribution characteristics of both species, revealing a boundary line at 29.00° N for L. uyii during the autumn, with the highest average individual weight occurring during the summer, with both larvae and juveniles occurring during the autumn. Thus, the life history of L. uyii can be divided into winter-spring nursery and summer-autumn spawning periods. L. beka showed a preference for inshore areas (15-60 m) during the summer and offshore areas (32.00-78.00 m) during the winter. High-value areas of both species included inshore areas of the southern Yellow and mid-East China Seas during the autumn, enlarging during the spring to include central areas of the survey region, before significantly decreasing during the summer. Therefore, this study provides both a novel perspective for modeling biological habitat distribution with limited data and a scientific basis for the adjustment of fishery resource management and conservation measures in the context of climate change.

A chromosome-level genome of the striated frogfish (Antennarius striatus).

The striated frogfish (Antennarius striatus), a member of the sub-order Antennarioidei within the order Lophiiformes, possesses remarkable adaptations. These include the ability to modulate body coloration for camouflage, utilize bioluminescent esca for predation, and employ elbow-like pectoral fins for terrestrial locomotion, making it a valuable model for studying bioluminescence, adaptive camouflage, fin-to-limb transition, and walking-like behaviors. To better study and contribute to the conservation of the striated frogfish, we obtained the micro-CT image of the pectoral fin bones and generated a high-quality, chromosome-level genome assembly using multiple sequencing technologies. The assembly spans 548.56 Mb with a contig N50 of 21.05 Mb, and 99.35% of the genome is anchored on 24 chromosomes, making it the most complete genome available within Lophiiformes. The genome annotation revealed 28.43% repetitive sequences and 23,945 protein-coding genes. This chromosome-level genome provides valuable genetic resources for frogfish conservation and offers insights into the genetic mechanisms underlying its unique phenotypic evolution. Furthermore, it establishes a foundation for future research on limb development and adaptive camouflage in this species.

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

Altered effective connectivity on rapid automatized naming deficits in Chinese children with developmental dyslexia: An rs-fMRI study with Ganger causality analysis.

Rapid Automatized Naming (RAN) is the core defect of developmental dyslexia (DD), requiring collaboration among brain areas to complete. However, it's still unclear which effective connectivity (EC) among brain areas are crucial for RAN deficits in Chinses children with DD. The current study aims to explore the EC among brain areas related to RAN deficits in Chinese children with DD. We recruited 36 Chinese children with DD and 64 typically developing (TD) children aged 8-12 to complete resting-state functional magnetic resonance imaging (rs-fMRI) scan. Granger causality analysis (GCA) was employed to analysis the EC among brain areas related to RAN, and to calculate the relationship between EC and RAN scores. Compared to TD group, the DD group exhibited significantly decreased EC from left precentral gyrus (PG) to right precuneus, left anterior cingulate and paracingulate gyrus (ACG), left calcarine and right angular, from left middle frontal gyrus (MFG) to left calcarine. Additionally, the DD group showed increased EC from right cuneus to left inferior frontal gyrus triangular part (IFGtri). The EC from left PG to left ACG was positively correlated with letters-RAN score. The results showed Chinese children with DD had both defect and compensatory mechanisms for their RAN deficits. The decreased EC output from left PG may be the core problem of the RAN deficits, which may influence the integration of visual-spatial information, attention, memory retrieval, and speech motor in speech production. The current study has important clinic implications for establishing intervention measures targeted brain.

Effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the Structure and Function of the Intestinal Flora in Rabbits Undergoing Hepatic Artery Infusion Chemotherapy.

Few studies have explored the biological mechanism by which probiotics alleviate adverse reactions to chemotherapy drugs after local hepatic chemotherapy perfusion by regulating the intestinal flora. This study investigates the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the intestinal microbial structure and intestinal barrier function, as well as the potential mechanism in rabbits after local hepatic chemotherapy infusion. Eighteen New Zealand White rabbits were randomly divided into a control group, a hepatic local chemotherapy perfusion group, and a hepatic local chemotherapy perfusion + Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets group to assess the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the adverse reactions. The administration of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets alleviated the intestinal flora disorder caused by local hepatic perfusion chemotherapy, promoted the growth of beneficial bacteria, and inhibited the growth of harmful bacteria. The Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets also reduced the levels of serum pro-inflammatory cytokines and liver injury factors induced by local hepatic perfusion chemotherapy. Our findings indicate that Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets can ameliorate the toxicity and side effects of chemotherapy by regulating intestinal flora, blocking pro-inflammatory cytokines, reducing liver injury factors, and repairing the intestinal barrier. Probiotics may be used as a potential alternative therapeutic strategy to prevent the adverse reactions caused by chemotherapy with local hepatic perfusion.

Comparison of three methods for collecting interstitial fluid from subcutaneous tissue in mini pigs.

Interstitial fluid, owing to its similarity to blood components and higher sensitivity and specificity, finds widespread application in disease diagnosis and tumor marker detection. However, collecting interstitial fluid, particularly from the deep subcutaneous connective tissue, remains challenging.•This study aimed to compare three different collection methods - push-pull perfusion, multi-filament nylon thread implantation, and tissue centrifugation - for collecting interstitial fluid from the subcutaneous connective tissue layer of mini-pigs. High-performance ion chromatography was employed to analyze the conventional cation components in the samples and compare ion composition analysis between the different methods.•Results indicated that while the distribution of conventional cations in the interstitial fluid collected by the three methods was generally consistent, there were slight variations in the detection rates and concentrations of different ions. Hence, suitable collection methods should be selected based on the ions or collection sites of interest.

Open access EEG dataset of repeated measurements from a single subject for microstate analysis.

Electroencephalography (EEG) microstate analysis is a neuroimaging analytical method that has received considerable attention in recent years and is widely used for analysing EEG signals. EEG is easily influenced by internal and external factors, which can affect the repeatability and stability of EEG microstate analysis. However, there have been few reports and publicly available datasets on the repeatability of EEG microstate analysis. In the current study, a 39-year-old healthy male underwent a total of 60 simultaneous electroencephalography and electrocardiogram measurements over a period of three months. After the EEG recording was completed, magnetic resonance imaging (MRI) was also conducted. To date, this EEG dataset has the highest number of repeated measurements for one individual. The dataset can be used to assess the stability and repeatability of EEG microstates and other analytical methods, to decode resting EEG states among subjects with open eyes, and to explore the stability and repeatability of cortical spatiotemporal dynamics through source analysis with individual MRI.

Effect of Transarterial Chemotherapy on the Structure and Function of Gut Microbiota in New Zealand White Rabbits.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host's GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut-liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

Bioaccumulation, trophic transfer and risk assessment of polycyclic musk in marine food webs of the Bohai Sea.

Galaxolide (HHCB) and tonalide (AHTN) are dominant musks added to personal care products. However, the accumulate and trophic transfer of SMs through the marine food chain are unclear. In this study, organisms were collected from three bays in Bohai Sea to investigate the bioaccumulation, trophic transfer, and health risk of SMs. The HHCB and AHTN concentrations in the muscles range from 2.75 to 365.40 µg/g lw and 1.04-4.94 µg/g lw, respectively. The median HHCB concentrations in muscles were the highest in Bohai Bay, followed by Laizhou Bay and Liaodong Bay, consistent with the HHCB concentrations in sediments. The different fish tissues from Bohai Bay were analyzed, and the HHCB and AHTN concentrations followed the heart > liver > gill > muscles. The trophic magnification factors (TMF) were lower than 1 and the health risk assessment showed no adverse health effects. The results provide insights into the bioaccumulation and trophic transfer behavior of SMs in marine environments.

A preliminary study on plasma concentration, short-term efficacy, and safety profile of dolutegravir in Chinese people with HIV.

BACKGROUND: This study examined the plasma concentration, clinical efficacy, and safety of dolutegravir (DTG) in Chinese people with HIV (PWH). METHODS: In this observational study, HIV-positive individuals on DTG-based regimens for at least 6 months were included. Plasma DTG concentrations were measured 1 month after initiating treatment. Viral loads (VL) and CD4+ T cell counts were evaluated at baseline and after 1 and 6 months of therapy. High-performance liquid chromatography was used for measuring DTG concentrations, polymerase chain reaction for VL, and flow cytometry for CD4+ T cell counts. Safety assessments included monitoring liver enzymes, serum creatinine estimated glomerular filtration rate, and adverse reactions. RESULTS: Eighty-two Chinese PWH were enrolled. Average VL decreased significantly from baseline by 3.1 log at 1 month and 3.5 log at 6 months. CD4+ T cell counts increased from 273 cells/mm3 at baseline to 378 cells/mm3 and 446 cells/mm3 after 1 and 6 months, respectively. Seventy-five percent achieved undetectable VLs (<20 copies/mL) by 6 months. Cmax and Cτ were 4.63 and 1.98 µg/mL, respectively. The safety profile was favorable with only 4.88% experiencing transient dizziness. CONCLUSION: Preliminary findings suggest higher DTG plasma concentrations in Chinese PWH compared to Western populations, with promising short-term efficacy and safety.

Characteristics of patients with initial diagnosis of systemic lupus erythematosus in emergency department and their outcomes: a retrospective single-center study.

STUDY OBJECTIVE: This study aims to investigate the characteristics of patients with an initial diagnosis of systemic lupus erythematosus (SLE) in an emergency department (ED) and their outcomes. METHODS: A total of 147 SLE patients (119 females and 28 males, mean age 26 ± 19 years) who visited the ED of the Peking University People's Hospital between January 2017 and June 2022 were enrolled in the study. Data on demographic information, clinical characteristics, comorbidities, therapy, and outcomes were collected. RESULTS: Most patients visit ED because of symptoms related to SLE (74.8%, 110/147). The remaining 37 patients (25.2%) visited ED due to infection (43.2%, 16/37), gastrointestinal bleeding (10.8%, 4/37), coronary heart or cerebrovascular disease (18.9%, 7/37), macrophage activation syndrome or thrombotic microangiopathy (18.9%, 7/37), leukemia (5.4%, 2/37), and hepatic encephalopathy (2.7%, 1/37). Of the patients, 54.4% (80/147) were first diagnosed with SLE at the time of their ED visit. Thrombocytopenia events occurred significantly more frequently in this group of patients (OR 3.664, 95% CI 1.586-8.464, p = 0.002). Pulse steroid therapy was administered to 32.5% (26/80) of the patients with an initial diagnosis of SLE, and 26.3% (21/80) of these patients also received IVIG therapy during their ED visit. SLEDAI scores were significantly decreased after 6 months of therapy. The rate of mortality was 6.8% (10/147) in the 6-month follow-up period, and all the ten deaths happened in patients with disease-established SLE. The main causes of death were infections (two patients) and SLE flare (four patients). CONCLUSION: Understanding disease patterns can contribute to physicians providing accurate diagnosis and efficient care for SLE patients in ED. Key Points • Systemic lupus erythematosus, a complex autoimmune disorder, can have either a chronic or a relapsing and remitting disease course. The disease can involve acute events or severe comorbidities, and frequent visits to the emergency department (ED) are inevitable. • It is essential to better understand which comorbidities can lead to emergency department visits. Accurate clinical diagnosis and appropriate interventions from ED physicians can have a strong impact on the prognosis of the disease. • Hematologic compromise attributed to SLE flare is the most common reason for ED visits. Owing to aggressive treatments, the clinical outcomes in patients with initial diagnosis of SLE have improved notably. • Our study highlights that early recognition and appropriate management of SLE-related conditions and other comorbidity in ED are crucial.

In vivo evaluation of liver function by multimodal imaging in an alcohol-induced liver injury model.

Background: Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in vivo in experimental studies. In this study, we established a multimodal imaging approach for in vivo liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research. Methods: In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by in vivo confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured. Results: In vivo multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice. Conclusions: Utilizing in vivo multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.

Protein Lactylation Modification and Proteomics Features in Cirrhosis Patients after UC-MSC Treatment.

Umbilical cord mesenchymal stem cell (UC-MSC) therapy improves liver function in liver cirrhosis patients. This study aimed to elucidate the therapeutic mechanism underlying cell therapy by analyzing changes in the modification and expression of proteins 1 month post-treatment with UC-MSCs. This prospective study included 11 cirrhosis patients who received MSC injection. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of UC-MSCs, and the protein expression and lactylation modification in the liver were comprehensively revealed. Meanwhile, weighted gene co-expression network analysis was used to analyze the co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving UC-MSC treatment; specifically, the liver protein synthesis function was significantly improved and the coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 lysine lactylation (Kla) sites of 119 proteins. Functional analysis showed that the lactylation-modified proteins were enriched in the pathway of glucose and other substances' metabolism, and many key enzymes of glycolysis and gluconeogenesis were lactated. UC-MSC therapy has a certain clinical effect in the treatment of liver cirrhosis and may act by regulating material metabolism, because the lactylation protein points to energy metabolism.

Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy.

Background: Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied. Methods: Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls. Results: Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism. Conclusions: Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.

Tidal Variations of Fish Larvae Measured Using a 15-Day Continuous Ichthyoplankton Survey in Subei Shoal: Management Implications for the Red-Crowned Crane (Grus japonensis) Population in Yancheng Nature Reserve.

The National Yancheng Rare Birds Nature Reserve is a vitally important staging habitat for the wild population of red-crowned cranes (Grus japonensis) in China. The population relies on local high-protein food sources, such as fish juveniles, to fuel their migratory journeys. However, little is known about the ecology of the fish larvae and juveniles that migrate to the inshore area via tidal rhythm in Subei Shoal, which is adjacent to the reserve. Therefore, we used a fixed study station (32°55'1.2″ N, 121°19'58.8″ E) to conduct a continuous 15-day ichthyoplankton survey at 2 h intervals beginning at 05:00 on 25 April and ending at 03:00 on 10 May 2019. We identified the tidal variations in the number of fish larvae and juveniles and the number at various developmental stages and assessed how they were related to environmental variables such as sea surface temperature, salinity, turbidity, and tidal height in the Dafeng Sea area of Subei Shoal. We found that the number of species and larval individuals were highest and lowest, respectively, at the highest and lowest tidal height, and they obviously increased and decreased with the rising and ebb tide, respectively. Our findings indicate that the variation in numbers of the larvae and juveniles depends on species and developmental stage. The species Acanthogobius ommaturus, Pholis fangi, Cynoglossus joyneri, Liza haematocheila, and Lateolabrax japonicus and the total number of larvae were most influenced by tidal height. These results provide a better understanding of the habitat of prey species of the red-crowned crane wild population as well as scientific data that can be applied to manage the wild population in the reserve sustainably.