Cancer-associated fibroblasts promote the progression and chemoresistance of HCC by inducing IGF-1.

Crosstalk between cancer-associated fibroblasts (CAFs) and tumour cells plays a critical role in multiple cancers, including hepatocellular carcinoma (HCC). CAFs contribute to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. However, effect and mechanism of CAF-mediated promotion of hepatocellular carcinoma cells are still unclear. In study, we demonstrated CAFs promoted the proliferation and inhibited the apoptosis of HCC cells by secreting interleukin-6 (IL-6), which induced autocrine insulin-like growth factor-1 (IGF-1) in HCC. IGF-1 promoted the progression and chemoresistance of HCC. IGF-1 receptor (IGF-1R) inhibitor NT157 abrogated the effect of CAF-derived IL-6 and autocrine IGF-1 on HCC. Mechanistic studies revealed that NT157 decreased IL-6-induced IGF-1 expression by inhibiting STAT3 phosphorylation and led to IRS-1 degradation, which mediated the proliferation of tumour by activating AKT signalling in ERK-dependent manner. Inhibition of IGF-1R also enhanced the therapeutic effect of sorafenib on HCC, especially chemoresistant tumours. STATEMENT OF SIGNIFICANCE: Our study showed IL-6-IGF-1 axis played crucial roles in the crosstalk between HCC and CAFs, providing NT157 inhibited of STAT3 and IGF-1R as a new targeted therapy in combination with sorafenib.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Lycium barbarum pulp addition improves the dough properties and gluten protein structure.

This study investigated the effects of Lycium barbarum pulp (LBP) on the properties of mixed dough and gluten protein. The results showed that appropriate addition of LBP (5 %) significantly improved the performance of the dough, promoted the aggregation of gluten protein, enhanced the water binding ability, and delayed the gelatinization of starch during cooking. Compared with the control group, the peak temperature (Tp) of the LBP sample gradually increased from 63.23 °C to 65.56 °C, the expansion force reduced by about 21.56 %, the absolute Zeta potential lowered by about 18.4 %, and the α -helix content and ß -folding increased by 32.36 % and 10.23 %, respectively, indicating the more orderly and stable overall structure. However, LBP did not change the crystal configuration of starch and still showed typical type A line diffraction. Moreover, the addition of LBP increased the polyphenol content, which further improved the antioxidant properties and provided the possibility to improve the health potential of the flour.

Dynamic changes in carbohydrate components and the bacterial community during the ensiling of wilted and unwilted sweet sorghum.

Sweet sorghum can be used to produce a substantial quantity of biofuel due to its high biological yield and high carbohydrate content. In this study, we investigated the dynamic changes in fermentation characteristics, carbohydrate components, and the bacterial community during the ensiling of wilted and unwilted sweet sorghum. The results revealed a rapid fermentation pattern and high-quality fermentation quality in wilted and unwilted sweet sorghum, wherein lactic acid, and acetic acid accumulated and stabilized during the initial 9 days of ensiling, with the pH values less than 4.2, until 60 days of ensiling. We found that the ensiling of sweet sorghum involved the degradation (5% ~ 10%) of neutral detergent fiber (NDF) and hemicellulose and that the degradation of NDF fit a first-order exponential decay model. A shift in dominance from Lactococcus to Lactobacillus occurred before the first 9 days of ensiling, and the abundance of Lactobacillus (r = -0.68, p < 0.001) was negatively correlated with the NDF content. The relative abundances of Lactobacillus in wilted and unwilted sweet sorghum after ensiling for 60 days were 76.30 and 93.49%, respectively, and relatively high fermentation quality was obtained. In summary, ensiling is proposed as a biological pretreatment for sweet sorghum for subsequent biofuel production, and unlike other materials, sweet sorghum quickly achieves good fermentation quality and has great potential for bioresource production.

Impact of body composition parameters, age, and tumor staging on gastric cancer prognosis.

BACKGROUND: Research studies on gastric cancer have not investigated the combined impact of body composition, age, and tumor staging on gastric cancer prognosis. To address this gap, we used machine learning methods to develop reliable prediction models for gastric cancer. METHODS: This study included 1,132 gastric cancer patients, with preoperative body composition and clinical parameters recorded, analyzed using Cox regression and machine learning models. RESULTS: The multivariate analysis revealed that several factors were associated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer. These factors included age (≥65 years), tumor-node-metastasis (TNM) staging, low muscle attenuation (MA), low skeletal muscle index (SMI), and low visceral to subcutaneous adipose tissue area ratios (VSR). The decision tree analysis for RFS identified six subgroups, with the TNM staging I, II combined with high MA subgroup showing the most favorable prognosis and the TNM staging III combined with low MA subgroup exhibiting the poorest prognosis. For OS, the decision tree analysis identified seven subgroups, with the subgroup featuring high MA combined with TNM staging I, II showing the best prognosis and the subgroup with low MA, TNM staging II, III, low SMI, and age ≥65 years associated with the worst prognosis. CONCLUSION: Cox regression identified key factors associated with gastric cancer prognosis, and decision tree analysis determined prognoses across different risk factor subgroups. Our study highlights that the combined use of these methods can enhance intervention planning and clinical decision-making in gastric cancer.

Analysis of D-dimer levels for the detection of deep venous thrombosis for patients with spinal metastasis undergoing decompression with fixation.

BACKGROUND: Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. METHODS: We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. RESULTS: Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. CONCLUSIONS: Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. TRIAL REGISTRATION: Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

Suitable fermentation temperature of forage sorghum silage increases greenhouse gas production: Exploring the relationship between temperature, microbial community, and gas production.

Silage is an excellent method of feed preservation; however, carbon dioxide, methane and nitrous oxide produced during fermentation are significant sources of agricultural greenhouse gases. Therefore, determining a specific production method is crucial for reducing global warming. The effects of four temperatures (10 °C, 20 °C, 30 °C, and 40 °C) on silage quality, greenhouse gas yield and microbial community composition of forage sorghum were investigated. At 20 °C and 30 °C, the silage has a lower pH value and a higher lactic acid content, resulting in higher silage quality and higher total gas production. In the first five days of ensiling, there was a significant increase in the production of carbon dioxide, methane, and nitrous oxide. After that, the output remained relatively stable, and their production at 20 °C and 30 °C was significantly higher than that at 10 °C and 40 °C. Firmicutes and Proteobacteria were the predominant silage microorganisms at the phylum level. Under the treatment of 20 °C, 30 °C, and 40 °C, Lactobacillus had already dominated on the second day of silage. However, low temperatures under 10 °C slowed down the microbial community succession, allowing, bad microorganisms such as Chryseobacterium, Pantoea and Pseudomonas dominate the fermentation, in the early stage of ensiling, which also resulted in the highest bacterial network complexity. According to random forest and structural equation model analysis, the production of carbon dioxide, methane and nitrous oxide is mainly affected by microorganisms such as Lactobacillus, Klebsiella and Enterobacter, and temperature influences the activity of these microorganisms to mediate gas production in silage. This study helps reveal the relationship between temperature, microbial community and greenhouse gas production during silage fermentation, providing a reference for clean silage fermentation.

The function and mechanism of Human nasal mucosa-derived mesenchymal stem cells in allergic rhinitis in mice.

PURPOSE: To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). METHOD: hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. RESULTS: MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. CONCLUSION: Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.

Half-dose ticagrelor versus standard-dose clopidogrel in a dual antiplatelet regimen for stent-assisted coiling or flow diversion of unruptured intracranial aneurysms: a cohort study.

BACKGROUND: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA). METHODS: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage. RESULTS: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889). CONCLUSION: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA.

[Prediction of Land Use and Habitat Quality in Harbin City Based on the PLUS- InVEST Model].

Analyzing the spatiotemporal evolution of urban land use and habitat quality can reveal the correlation between land use and habitat quality, aiding in rational urban land policies and high-quality ecological environment development. This study was based on land use transition matrices and an Intensity-Migration （IM） model to analyze the changes in land use in Harbin from 2000 to 2020. It combined the PLUS model to explore the driving factors of land use expansion for various land types and predicted land use scenarios for 2030 under natural development, ecological protection, farmland protection, and urban development scenarios. Finally, the InVEST model was used to complete the habitat quality analysis. The results indicated： ① The dominant land use types in Harbin were cropland, forest land, and grassland. From 2000 to 2020, there was a significant tendency of conversion into grassland, cropland, forest land, and artificial surfaces, with noticeable changes in land use intensity. Water bodies, bare land, and wetland types showed less conversion and tended to be restrictive. ② Elevation was the primary factor influencing the expansion of grassland, cropland, forest land, bare land, wetland, and water bodies. Socioeconomic factors were the main factor affecting the expansion of artificial surfaces. ③ Simulation of land use types in Harbin for 2030 under the four scenarios showed an increase in forest land area and a decrease in grassland area, with insignificant changes in wetland, water bodies, and bare land areas. Except for in the ecological protection scenario, the area of artificial surfaces increased, whereas cropland decreased. ④ Overall, habitat quality in Harbin improved from 2000 to 2020. ⑤ In 2030, the spatial pattern of habitat quality in Harbin remained consistent across all scenarios, showing an overall improvement in habitat quality. Under the ecological protection scenario, areas with low and medium habitat quality decreased, whereas areas with higher habitat quality increased, indicating a relatively significant improvement in habitat quality. The research results provide a scientific basis and insights for the development of ecological civilization and urban planning and construction in Harbin.

Metabolic profiling of idiopathic pulmonary fibrosis in a mouse model: implications for pathogenesis and biomarker discovery.

Background: Alterations in metabolites and metabolic pathways are thought to be important triggers of idiopathic pulmonary fibrosis (IPF), but our lack of a comprehensive understanding of this process has hampered the development of IPF-targeted drugs. Methods: To fully understand the metabolic profile of IPF, C57BL/6 J male mice were injected intratracheally with bleomycin so that it could be used to construct a mouse model of IPF, and lung tissues from 28-day and control IPF mice were analyzed by pathology and immunohistochemistry. In addition, serum metabolites from IPF mice were examined using LC-ESI-MS/MS, and the differential metabolites were analyzed for KEGG metabolic pathways and screened for biomarkers using machine learning algorithms. Results: In total, the levels of 1465 metabolites were detected, of which 104 metabolites were significantly altered after IPF formation. In IPF mouse serum, 52% of metabolite expression was downregulated, with lipids (e.g., GP, FA) and organic acids and their derivatives together accounting for more than 70% of the downregulated differentially expressed metabolites. In contrast, FA and oxidised lipids together accounted for 60% of the up-regulated differentially expressed metabolites. KEGG pathway enrichment analyses of differential metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism. Seven metabolites were screened by machine learning LASSO models and evaluated as ideal diagnostic tools by receiver operating characteristic curves (ROCs). Discussion: In conclusion, the serum metabolic disorders found to be associated with pulmonary fibrosis formation will help to deepen our understanding of the pathogenesis of pulmonary fibrosis.

Fermentation Parameters, Amino Acids Profile, Biogenic Amines Formation, and Bacterial Community of Ensiled Stylo Treated with Formic Acid or Sugar.

Substantial proteolysis occurs and free amino acids can be degraded to biogenic amines by decarboxylation during stylo (Stylosanthes guianensis) ensiling. High biogenic amine concentrations in silage are harmful to the health of ruminant animals. The purposes of this work were to (1) analyze the biogenic amines and amino acids concentrations, bacterial composition, and fermentation profile of spontaneously fermented stylo silage, (2) explore the effect of formic acid or sugar additive on these silage parameters, and (3) further reveal the correlations between silage amines and fermentation parameters, amino acids, and bacteria. Freshly chopped stylo was treated with distilled water (control), formic acid (4 mL/kg), and sugar (20 g/kg) and fermented for 28 days. The results indicated that putrescine (321 mg/kg dry matter), cadaverine (384 mg/kg dry matter), and tyramine (127 mg/kg dry matter) rapidly increased in concentration and become predominant in the control silage after 28 days of fermentation. Applying formic acid and sugar at ensiling, especially the acidifier, significantly decreased putrescine, cadaverine, tyramine, and total biogenic amine concentrations compared with the control treatment (p < 0.0001). Clostridium pabulibutyricum, Weissella cibaria and W. paramesenteroides were the predominant bacteria in the control silage, and the application of both additives remarkably lowered their relative abundance in comparison with the control treatment (p < 0.001). Correlation analysis showed that putrescine, cadaverine, and tyramine were positively related to pH, butyric acid, non-protein nitrogen, and ammonia nitrogen (p < 0.01). These amines also had significant correlations with C. pabulibutyricum, W. cibaria and W. paramesenteroides (p < 0.001). Putrescine, cadaverine, and tyramine were the main biogenic amines and C. pabulibutyricum was the predominant undesirable bacterium in naturally fermented stylo silage. C. pabulibutyricum, W. cibaria and W. paramesenteroides were positively related to putrescine, cadaverine, and tyramine formation. The application of formic acid or sugar significantly reduced the undesirable bacterial population and improved the fermentation and hygienic quality of the stylo silage. These findings lay the foundation for further elucidating the microbial mechanism underlying the main biogenic amine formation during fermentation of stylo silage.

HTB50-2 Inhibits Growth and Migration of Triple-negative Breast Cancer via FOSL2/FOXC1 Signaling Axis and Subsequent Ferroptosis.

BACKGROUND: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14ß-hydroxy- 3ß-(ß-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms. METHODS: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed. RESULTS: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis. CONCLUSION: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC.

Functional Characterization of JcSWEET12 and JcSWEET17a from Physic Nut.

Physic nut (Jatropha curcas L.) has attracted extensive attention because of its fast growth, easy reproduction, tolerance to barren conditions, and high oil content of seeds. SWEET (Sugar Will Eventually be Exported Transporter) family genes contribute to regulating the distribution of carbohydrates in plants and have great potential in improving yield and stress tolerance. In this study, we performed a functional analysis of the homology of these genes from physic nut, JcSWEET12 and JcSWEET17a. Subcellular localization indicated that the JcSWEET12 protein is localized on the plasma membrane and the JcSWEET17a protein on the vacuolar membrane. The overexpression of JcSWEET12 (OE12) and JcSWEET17a (OE17a) in Arabidopsis leads to late and early flowering, respectively, compared to the wild-type plants. The transgenic OE12 seedlings, but not OE17a, exhibit increased salt tolerance. In addition, OE12 plants attain greater plant height and greater shoot dry weight than the wild-type plants at maturity. Together, our results indicate that JcSWEET12 and JcSWEET17a play different roles in the regulation of flowering time and salt stress response, providing a novel genetic resource for future improvement in physic nut and other plants.

Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.

Partial response of hepatocellular carcinoma to lenalidomide following progression in response to lenvatinib: A case report.

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.

Enhancing immunogenicity and antiviral protection of inactivated porcine reproductive and respiratory syndrome virus vaccine in piglets.

OBJECTIVE: Porcine interferon-γ (poIFN-γ) and porcine granulocyte-macrophage colony-stimulating factor (poGM-CSF) are multifunctional cytokines that exhibit robust antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the immunoadjuvant effects of recombinant poIFN-γ-poGM-CSF fusion protein in inactivated PRRSV vaccine administered to piglets were assessed. ANIMALS: Twenty-eight 4-week-old specific pathogen-free piglets. METHODS: The experimental piglets were divided into control, highly pathologic PRRSV, PRRSV killed virus vaccine (KV), poIFN-γ-poGM-CSF, KV + 1.0 mg poIFN-γ-poGM-CSF, KV + 2.0 mg poIFN-γ-poGM-CSF, and KV + 4.0 mg poIFN-γ-poGM-CSF groups. A recombinant poIFN-γ-linker-poGM-CSF fusion gene was constructed via splicing by overlap extension PCR and prepared using an Escherichia coli expression system, after which its adjuvant activity in the context of PRRSV KV administration was assessed. RESULTS: This analysis revealed the successful construction of the poIFN-γ-linker-poGM-CSF fusion gene via splicing by overlap extension PCR, with recombinant poIFN-γ-linker-poGM-CSF successfully being prepared in E coli with a plasmid vector for expressing thioredoxin fusion proteins with an enterokinase site. Importantly, the coadministration of poIFN-γ-linker-poGM-CSF and PRRSV KV significantly increased neutralizing antibody titers, accelerated viral clearance, reduced clinical symptoms, and prevented highly pathogenic PRRSV infection. CLINICAL RELEVANCE: The recombinant poIFN-γ-poGM-CSF fusion protein is a promising candidate adjuvant for use in the context of swine immunization and viral challenge.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Effect of Regulation of Whole-Plant Corn Silage Inoculated with Lactobacillus buchneri or Bacillus licheniformis Regarding the Dynamics of Bacterial and Fungal Communities on Aerobic Stability.

Enhancing the aerobic stability of whole-plant corn silage is essential for producing high-quality silage. Our research assessed the effect of inoculation with Lactobacillus buchneri or Bacillus licheniformis and its modulation of the bacterial and fungal microbial community structure in an aerobic stage of whole-plant corn silage. Following treatment with a distilled sterile water control, Lactobacillus buchneri, and Bacillus licheniformis (2 × 105 cfu/g), whole-plant corn was ensiled for 60 days. Samples were taken on days 0, 3, and 7 of aerobic exposure, and the results showed that inoculation with Lactobacillus buchneri or Bacillus licheniformis improved the aerobic stability of silage when compared to the effect of the control (p < 0.05). Inoculation with Bacillus licheniformis attenuated the increase in pH value and the decrease in lactic acid in the aerobic stage (p < 0.05), reducing the filamentous fungal counts. On the other hand, inoculation with Lactobacillus buchneri or Bacillus licheniformis increased the diversity of the fungal communities (p < 0.05), complicating the correlation between bacteria or fungi, reducing the relative abundance of Acetobacter and Paenibacillus in bacterial communities, and inhibiting the tendency of Monascus to replace Issatchenkia in fungal communities, thus delaying the aerobic spoilage process. Due to the prevention of the development of aerobic spoilage microorganisms, the silage injected with Lactobacillus buchneri or Bacillus licheniformis exhibited improved aerobic stability.