Kokusaginine attenuates renal fibrosis by inhibiting the PI3K/AKT signaling pathway.

Kokusaginine is an active ingredient alkaloid that has been isolated and extracted from Ruta graveolens L. Some researches have indicated that alkaloids possess anti-inflammatory and antioxidant effects. Nevertheless, the potential nephroprotective effects of kokusaginine on renal fibrosis remain undetermined. This study was conducted to examine the protective effect of kokusaginine on renal fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. Renal fibrosis was induced in male C57BL/6 J mice by feeding with 0.2% adenine-containing food and UUO surgery. Kokusaginine was administered orally simultaneously after the establishment of renal fibrosis. Renal function was measured by serum levels of creatinine and urea nitrogen. Renal pathological changes were assessed by HE staining and Masson staining. Western blotting was employed to detect the expression levels of fibrosis-related proteins in mice and cells. Additionally, network pharmacology analysis and RNA-seq were utilized to predict the pathways through which kokusaginine could exert its anti-fibrotic effects. The treatment with kokusaginine enhanced renal function, alleviated renal histoarchitectural lesions, and mitigated renal fibrosis in the renal fibrosis models. The network pharmacology and RNA-seq enrichment analysis of the KEGG pathway demonstrated that kokusaginine could exert anti-renal fibrosis activity via the PI3K/AKT signaling pathway. And the results were verified in both in vitro and in vivo experiments. In conclusion, our data implied that kokusaginine inhibited the activation of the PI3K/AKT signaling pathway both in vitro and in vivo, and suppressed the formation of renal fibrosis. Thus, the kokusaginine-mediated PI3K/AKT signaling pathway may represent a novel approach for the treatment of renal fibrosis.

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Exploration of prognostic and treatment markers in hepatocellular carcinoma via GPCR-related genes analysis.

Background: G protein-coupled receptors (GPCRs), the biggest family of signaling receptors, account for 34 % of all the drug targets approved by the Food and Drug Administration (FDA). It has been gradually recognized that GPCRs are of significance for tumorigenesis, but in-depth studies are still required to explore specific mechanisms. In this study, the role of GPCRs in hepatocellular carcinoma (HCC) was elucidated, and GPCR-related genes were employed for building a risk-score model for the prognosis and treatment efficacy prediction of HCC patients. Methods: Patients' data on HCC were sourced from the Liver Hepatocellular Carcinoma-Japan (LIRI-JP) and The Cancer Genome Atlas (TCGA) databases, while GPCR-related genes were obtained from the Molecular Signatures Database (MSigDB). Univariant and multivariant Cox regression analyses, as well as least absolute shrinkage and selection operator (LASSO) were performed with the aim of identifying differentially expressed GPCR-related genes and grouping patients. Differential expression and functional enrichment analyses were performed; protein-protein interaction (PPI) mechanisms were explored; hub genes and micro ribonucleic acid (miRNA)-target gene regulatory networks were constructed. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to evaluate immune infiltration levels and genetic variations. Sensitivity to immunotherapy and common antitumor drugs was predicted via the database Genomics of Drug Sensitivity in Cancer (GDSC). Results: A GPCR-related risk score containing eight GPCR-related genes (atypical chemokine receptor 3 (ACKR3), C-C chemokine receptor type 3 (CCR3), CCR7, frizzled homolog 5 (FZD5), metabotropic glutamate receptor 8 (GRM8), hydroxycarboxylic acid receptor 1 (HCAR1), 5-hydroxytryptamine receptor 5A (HTR5A) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6)) was set up. In addition, patients were classified into groups with high and low risks. Patients in the high-risk group exhibited a worse prognosis but demonstrated a more favorable immunotherapy response rate compared with those in the low-risk group. Distinct sensitivity to chemotherapeutic drugs was observed. A clinical prediction model on the basis of GPCR-related risk scores was constructed. Areas under the curves (AUC) corresponding to one-, three- and five-year survival were 0.731, 0.765 and 0.731, respectively. Conclusions: In this study, an efficient HCC prognostic prediction model was constructed by only GPCR-related genes, which are all potential targets for HCC treatment.

Tackling Antibiotic Resistance: Exploring 5-Fluorouracil as a Promising Antimicrobial Strategy for the Treatment of Streptococcus suis Infection.

Streptococcus suis (S. suis) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis, are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Demonstration Study of Reflector-Based Volumetric Speed-of-Sound Imaging With Linear Ultrasound Arrays.

Conventional B-mode ultrasound imaging has difficulty in delineating homogeneous soft tissues with similar acoustic impedances, as the reflectivity depends on the acoustic impedance at the interface. As a quantitative imaging biomarker sensitive to alteration of biomechanical properties, speed-of-sound (SoS) holds promising potential for tissue and disease differentiation such as delineation of different breast tissue types with similar acoustic impedance. Compared to two-dimensional (2D) SoS images, three-dimensional (3D) volumetric SoS images achieved through a full-angle ultrasound scan can reveal more intricate morphological structures of tissues; however, they generally require a ring transducer. In this study, we introduce a 3D SoS reconstruction system that utilizes hand-held linear arrays instead. This system employs a passive reflector positioned opposite the linear arrays, serving as an echogenic reference for time-of-flight (ToF) measurements, and a high-definition camera to track the location corresponding to each group of transmit-receive data. To merge these two streams of ToF measurements and location tracking, a voxel-based reconstruction algorithm is implemented. Experimental results with gelatin phantom and ex vivo tissue have demonstrated the stability of our proposed method. Moreover, the results underscore the potential of this system as a complementary diagnostic modality, particularly in the context of diseases such as breast cancer.

Deep learning-based arterial subtraction images improve the detection of LR-TR algorithm for viable HCC on extracellular agents-enhanced MRI.

PURPOSE: To determine the role of deep learning-based arterial subtraction images in viability assessment on extracellular agents-enhanced MRI using LR-TR algorithm. METHODS: Patients diagnosed with HCC who underwent locoregional therapy were retrospectively collected. We constructed a deep learning-based subtraction model and automatically generated arterial subtraction images. Two radiologists evaluated LR-TR category on ordinary images and then evaluated again on ordinary images plus arterial subtraction images after a 2-month washout period. The reference standard for viability was tumor stain on the digital subtraction hepatic angiography within 1 month after MRI. RESULTS: 286 observations of 105 patients were ultimately enrolled. 157 observations were viable and 129 observations were nonviable according to the reference standard. The sensitivity and accuracy of LR-TR algorithm for detecting viable HCC significantly increased with the application of arterial subtraction images (87.9% vs. 67.5%, p < 0.001; 86.4% vs. 75.9%, p < 0.001). And the specificity slightly decreased without significant difference when the arterial subtraction images were added (84.5% vs. 86.0%, p = 0.687). The AUC of LR-TR algorithm significantly increased with the addition of arterial subtraction images (0.862 vs. 0.768, p < 0.001). The arterial subtraction images also improved inter-reader agreement (0.857 vs. 0.727). CONCLUSION: Extended application of deep learning-based arterial subtraction images on extracellular agents-enhanced MRI can increase the sensitivity of LR-TR algorithm for detecting viable HCC without significant change in specificity.

Tick-borne Rickettsia, Anaplasma, Theileria, and enzootic nasal tumor virus in ruminant, PET, and poultry animals in Pakistan.

Introduction: Pakistan is an agricultural country; most of its income is based on livestock rearing. The increasing prevalence of tick-borne pathogens among animals may affect the animal production and livelihood of owners, which eventually derange the economy of a country. Methodology: To further comprehend TBPs, 213 ticks were collected from different animals, including ruminants, pets, and poultry. After molecular and phylogenetic analysis identification, ticks were managed into different pools based on their species level (Hyalomma anatolicum = 80, Rhipicephalus microplus = 35, Hyalomma scupense = 23, Rhipicephalus turanicus = 70, and Rhipicephalus sanguineus = 5). Results and discussion: After tick species identification, further molecular PCR amplification was carried out to screen out the pathogens for the presence of Theileria, Rickettsia, Anaplasma, and enzootic nasal tumor virus (ENTV). The following pathogens were detected: 11 (5.16%) for Anaplasma, 1 (0.47%) for Rickettsia, and 9 (4.23%) for Theileria. Nevertheless, other TBPs that had not been reported so far in Pakistan 3 (1.41%), were positive for enzootic nasal tumor virus (ENTV). Besides, phylogenetic analysis of the enzootic nasal tumor virus (ENTV) strain confirmed its resemblance to the Chinese strain, while Anaplasma has comparability with Pakistan and China, Rickettsia with Pakistan, China, and Iran, and Theileria with India, South Africa, United States, Japan, and Spain. Conclusion: This study reveals that there is a considerably wider range of TBPs held in Pakistan that take in various contagious zoonotic pathogens than was previously thought. This information advances TBP epidemiology and will contribute to upgrade future control measure.

Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis.

Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.

The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization.

Recent studies have revealed that PTPRZ1-MET (ZM) fusion plays a pivotal role in the progression of glioma to glioblastoma multiforme (GBM), thus serving as a biomarker to distinguish between primary GBM and secondary GBM (sGBM). However, the mechanisms through which ZM fusion influences this progression remain to be elucidated. GBMs with ZM showed poorer prognoses and greater infiltration of tumor-associated macrophages (TAMs) than those without ZM. Glioma stem-like cells (GSCs) and TAMs play complex roles in glioma recurrence, glioma progression and therapy resistance. In this study, we analyzed RNA-seq data from sGBM patients' glioma tissues with or without ZM fusion, and found that stemness and macrophage markers were more highly expressed in sGBM patients harboring ZM than in those without ZM fusion. ZM enhanced the self-renewal and proliferation of GSCs, thereby accelerating glioma progression. In addition, ZM-positive GSCs facilitated the infiltration of TAMs and drove their polarization toward an immunosuppressive phenotype, which was primarily accomplished through the extracellular secretion of ISG20. Our research identified the MET-STAT3-ISG20 axis within GSCs, thus demonstrating the critical role of ZM in GBM initiation and progression. Our study demonstrated that, in contrast to ZM-positive differentiated glioma cells, ZM-positive GSCs upregulated ISG20 expression through the MET-STAT3-ISG20 axis. The extracellular secretion of ISG20 recruited and induced M2-like polarization in macrophages, thereby promoting tumor progression. Our results reveal a novel mechanism involved in ZM-positive GBM pathogenesis and identify potential therapeutic targets.

Acidity-Triggered "Sticky Spotlight": CCK2R-Targeted TME-Sensitive NIR Fluorescent Probes for Tumor Imaging In Vivo.

Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5-6.8) and lysosomes (pH = 4.5-5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Microencapsulation with fructooligosaccharides and whey protein enhances the antioxidant activity of anthocyanins and their ability to modulate gut microbiota in vitro.

Anthocyanins are the primary functional pigments in the diet. However, anthocyanins exhibit instability during digestion, coupled with limited bioavailability. Microencapsulation offers anthocyanins a sheltered environment, enhancing their stability and bioactivity. Fructooligosaccharides (FOS) and whey protein (WP) commonly serve as wall materials in microencapsulation and represent a significant source of probiotic functionality. Our prior research successfully established a robust microencapsulation system for anthocyanins utilizing FOS and WP. This study investigates the antioxidative capacity, stability during in vitro digestion, modulation on gut microbiota, and short-chain fatty acids (SCFAs) production of black soybean skin anthocyanins microencapsulated with FOS and WP (anthocyanin-loaded microencapsule particles, ALM). The results demonstrate that ALM exhibits a superior antioxidant capacity compared to free anthocyanins (ANCs) and cyanidin-3-glucoside (C3G). During simulated digestion, ALM exhibits enhanced anthocyanin retention compared with ANC in both gastric and intestinal phases. In comparison with ANC and even non-loaded microcapsules (NLM), in vitro fermentation demonstrates that ALM exhibits the highest gas production and lowered pH, indicating excellent fermentation activity. Furthermore, in comparison with ANC or NLM, ALM exerts a positive influence on the diversity and composition of gut microbiota, with potentially beneficial genera such as Faecalibacterium and Akkermansia exhibiting higher relative abundance. Moreover, ALM stimulates the production of SCFAs, particularly acetic and propionic acids. In conclusion, microencapsulation of anthocyanins with FOS-WP enhances their antioxidative capacity and stability during in vitro digestion. Simultaneously, this microencapsulation illustrates a positive regulatory effect on the intestinal microbiota community and SCFA production, conferring potential health benefits.

Cell fusion between tumor cells and macrophages promotes the metastasis of OSCC patient through the activation of the chemokine signaling pathway.

BACKGROUND: Tumor metastasis is responsible for the high mortality rate of patients with oral squamous cell carcinoma (OSCC). Although many hypotheses have been proposed to elucidate the mechanism of tumor metastasis, the origin of the metastatic tumor cells remains unclear. In this study, we explored the role of cell fusion in the formation of OSCC metastatic tumor cells. METHODS: Murine OSCC tumor cells and macrophages were fused in vitro, and the cell proliferation, migration, and phagocytosis abilities of hybrid cells and parental cells were compared. Subsequently, we compared the transcriptome differences between hybrid and parental cells. RESULTS: Murine OSCC tumor cells and macrophages were successfully fused in vitro. The cytological and molecular experimental results revealed that OSCC tumor cells obtained a migration-related phenotype after fusion with macrophages, and the migration ability of hybrid cells was related to the activation of the "chemokine signal pathway". CONCLUSION: After fusion with macrophages, the chemokine signaling pathway in OSCC tumor cells was activated, leading to metastasis.

Reliable Delineation of Clinical Target Volumes for Cervical Cancer Radiotherapy on CT/MR Dual-Modality Images.

Accurate delineation of the clinical target volume (CTV) is a crucial prerequisite for safe and effective radiotherapy characterized. This study addresses the integration of magnetic resonance (MR) images to aid in target delineation on computed tomography (CT) images. However, obtaining MR images directly can be challenging. Therefore, we employ AI-based image generation techniques to "intelligentially generate" MR images from CT images to improve CTV delineation based on CT images. To generate high-quality MR images, we propose an attention-guided single-loop image generation model. The model can yield higher-quality images by introducing an attention mechanism in feature extraction and enhancing the loss function. Based on the generated MR images, we propose a CTV segmentation model fusing multi-scale features through image fusion and a hollow space pyramid module to enhance segmentation accuracy. The image generation model used in this study improves the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) from 14.87 and 0.58 to 16.72 and 0.67, respectively, and improves the feature distribution distance and learning-perception image similarity from 180.86 and 0.28 to 110.98 and 0.22, achieving higher quality image generation. The proposed segmentation method demonstrates high accuracy, compared with the FCN method, the intersection over union ratio and the Dice coefficient are improved from 0.8360 and 0.8998 to 0.9043 and 0.9473, respectively. Hausdorff distance and mean surface distance decreased from 5.5573 mm and 2.3269 mm to 4.7204 mm and 0.9397 mm, respectively, achieving clinically acceptable segmentation accuracy. Our method might reduce physicians' manual workload and accelerate the diagnosis and treatment process while decreasing inter-observer variability in identifying anatomical structures.

Ferrostatin-1 improves prognosis and regulates gut microbiota of steatotic liver transplantation recipients in rats.

Aims: To investigate the effects of Ferrostatin-1 (Fer-1) on improving the prognosis of liver transplant recipients with steatotic liver grafts and regulating gut microbiota in rats. Methods: We obtained steatotic liver grafts and established a liver transplantation model. Recipients were divided into sham, liver transplantation and Fer-1 treatment groups, which were assessed 1 and 7 days after surgery (n = 6). Results & conclusion: Fer-1 promotes recovery of the histological structure and function of steatotic liver grafts and the intestinal tract, and improves inflammatory responses of recipients following liver transplantation. Fer-1 reduces gut microbiota pathogenicity, and lowers iron absorption and improves fat metabolism of recipients, thereby protecting steatotic liver grafts.

Differences of serum glucose and lipid metabolism and immune parameters and blood metabolomics regarding the transition cows in the antepartum and postpartum period.

This study aims to investigate differences in metabolism regarding the transition cows. Eight cows were selected for the test. Serum was collected on antepartum days 14th (ap14) and 7th (ap7) and postpartum days 1st (pp1), 7th (pp7), and 14th (pp14) to detect biochemical parameters. The experiment screened out differential metabolites in the antepartum (ap) and postpartum (pp) periods and combined with metabolic pathway analysis to study the relationship and role between metabolites and metabolic abnormalities. Results: (1) The glucose (Glu) levels in ap7 were significantly higher than the other groups (p < 0.01). The insulin (Ins) levels of ap7 were significantly higher than pp7 (p = 0.028) and pp14 (p < 0.01), and pp1 was also significantly higher than pp14 (p = 0.016). The insulin resistance (HOMA-IR) levels of ap7 were significantly higher than ap14, pp7, and pp14 (p < 0.01). The cholestenone (CHO) levels of ap14 and pp14 were significantly higher than pp1 (p < 0.01). The CHO levels of pp14 were significantly higher than pp7 (p < 0.01). The high density lipoprotein cholesterol (DHDL) levels of pp1 were significantly lower than ap14 (p = 0.04), pp7 (p < 0.01), and pp14 (p < 0.01), and pp14 was also significantly higher than ap14 and ap7 (p < 0.01). (2) The interferon-gamma (IFN-γ) and tumor necrosis factor α (TNF-α) levels of ap7 were significantly higher than pp1 and pp7 (p < 0.01); the immunoglobulin A (IgA) levels of pp1 were significantly higher than ap7 and pp7 (p < 0.01); the interleukin-4 (IL-4) levels of pp7 were significantly higher than ap7 and pp1 (p < 0.01), the interleukin-6 (IL-6) levels of ap7 and pp1 were significantly higher than pp7 (p < 0.01). (3) Metabolomics identified differential metabolites mainly involved in metabolic pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism, tyrosine metabolism, and lysine degradation. The main relevant metabolism was concentrated in lipid and lipid-like molecules, organic heterocyclic compounds, organic acids, and their derivatives. The results displayed the metabolic changes in the transition period, which laid a foundation for further exploring the mechanism of metabolic abnormalities in dairy cows in the transition period.

Traditional Uses, Chemical Constituents and Pharmacological Activities of the Toona sinensis Plant.

Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1-133), sesquiterpenoids (134-135), diterpenoids (136-142), sterols (143-147), phenols (148-167), flavonoids (168-186), phenylpropanoids (187-192) and others (193-206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154-156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value.

The timing phase affected the inconsistency of APHE subtypes of liver observations in patients at risk for HCC on the multi-hepatic arterial phase imaging.

OBJECTIVE: To investigate whether liver observations in patients at risk for hepatocellular carcinoma (HCC) display inconsistent arterial phase hyperenhancement (APHE) subtypes on the multi-hepatic arterial phase imaging (mHAP) and to further investigate factors affecting inconsistent APHE subtype of observations on mHAP imaging. METHODS: From April 2018 to June 2021, a total of 141 patients at high risk of HCC with 238 liver observations who underwent mHAP MRI acquisitions were consecutively included in this retrospective study. Two experienced radiologists reviewed individual arterial phase imaging independently and assessed the enhancement pattern of each liver observation according to LI-RADS. Another two experienced radiologists identified and recorded the genuine timing phase of each phase independently. When a disagreement appeared between the two radiologists, another expert participated in the discussion to get a final decision. A separate descriptive analysis was used for all observations scored APHE by the radiologists. The Kappa coefficient was used to determine the agreement between the two radiologists. Univariate analysis was performed to investigate the factors affecting inconsistent APHE subtype of liver observations on mHAP imaging. RESULTS: The interobserver agreement was substantial to almost perfect agreement on the assessment of timing phase (κ = 0.712-0.887) and evaluation of APHE subtype (κ = 0.795-0.901). A total of 87.8% (209/238) of the observations showed consistent nonrim APHE and 10.2% (24/238) of the observations showed consistent rim APHE on mHAP imaging. A total of 2.1% (5/238) of the liver observations were considered inconsistent APHE subtypes, and all progressed nonrim to rim on mHAP imaging. 87.9% (124/141) of the mHAP acquisitions were all arterial phases and 12.1% (17/141) of the mHAP acquisitions obtained both the arterial phase and portal venous phase. Univariate analysis was performed and found that the timing phase of mHAP imaging affected the consistency of APHE subtype of liver observations. When considering the timing phase and excluding the portal venous phase acquired by mHAP imaging, none of the liver observations showed inconsistent APHE subtypes on mHAP imaging. CONCLUSION: The timing phase which mHAP acquisition contained portal venous phase affected the inconsistency of APHE subtype of liver observations on mHAP imaging. When evaluating the APHE subtype of liver observations, it's necessary to assess the timing of each phase acquired by the mHAP technique at first.

Perceptions of adult patients with cancer towards telemedicine: A qualitative meta-synthesis.

Objective: This study aims to systematically identify, evaluate, and synthesize published qualitative research on the views and attitudes of adult cancer patients toward telemedicine and, consequently to better inform the future development of telemedicine technology and interventions. Methods: A meta-synthesis review was conducted to identify qualitative studies that reported adult cancer patients' perceptions toward telemedicine applications using nine electronic databases, including PubMed, MEDLINE, Web of Science, the Cochrane Library, PsycINFO, CINAHL, Wan Fang, VIP, and CNKI, from inception to November 2022. Quality appraisal was guided by the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist for Qualitative Research. Data were synthesized using "thematic synthesis" to identify themes and concepts. Results: A total of 3518 articles were retrieved, of which 23 met the inclusion and exclusion criteria. These studies identified three key meta-themes and 11 key sub-themes: (1) Benefits of telemedicine: obtaining information and social support, maintaining the continuity of treatment, receiving professional assistance, having greater flexibility, and promoting physical and mental health; (2) Limitations of telemedicine: interference with normal life, privacy and security issues, auxiliary function issues, and increased psychological burden; (3) Expectations for future telemedicine: more personalized intervention, more specific and diverse information. Conclusions: The study showed that the benefits and limitations coexisted in the process of telemedicine application among adult cancer patients. It is necessary to develop personalized applications that are better suited to the needs and characteristics of adult cancer patients. Future telemedicine interventions should focus on information diversification and provide patients with more diverse and effective information. Systematic review registration: PROSPERO, CRD42022324528.