An Immunomodulatory Hydrogel by Hyperthermia-Assisted Self-Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics.

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia-caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self-cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin-incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia-enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS-inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.

Mild Photothermal Therapy Prevents Posterior Capsule Opacification through Cytoskeletal Remodeling.

Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.

Metformin modified chitosan as a multi-functional adjuvant to enhance cisplatin-based tumor chemotherapy efficacy.

Recently, it was newly revealed that the DNA damage induced by cis­platinum (Cis-Pt) mediated chemotherapy was significantly impaired by the highly expressed programmed death ligand-1 (PD-L1) in tumor cells. Besides, the efficacy of Cis-Pt was also limited due to its severe side effects, especially enhanced drug efflux induced by multidrug resistance protein 1 (MDR-1) and increased tumor metastasis. Up to now, few drugs or carbohydrates could simultaneously solve these defects of Cis-Pt mediated chemotherapy. Here, we newly found that metformin-modified chitosan (Ch-Met) possessed ideal selective mitochondria accumulation capacity, leading to the further disrupted mitochondrial function, which then effectively inhibited the upregulated PD-L1 expression to inhibit DNA damage repair in tumor cells, as well as impaired drug efflux and lowered tumor metastasis. Therefore, it was demonstrated that Ch-Met could sensitize the chemotherapy efficacy of Cis-Pt.

Mild Hyperthermia-Assisted ROS Scavenging Hydrogels Achieve Diabetic Wound Healing.

Excessive reactive oxygen species (ROS) production induces oxidative damage to biomolecules, which can lead to the development of chronic diseases. Biocompatible hydrogel antioxidants composed of natural materials, such as polysaccharides and polyphenols, are of significant option for ROS scavenging. However, rapidly achieving hydrogel antioxidants with convenient, economical, safe, and efficient features remains challenging. Herein, facile synthesis of a physically cross-linked polyphenol/polysaccharide hydrogel by introducing tannic acid microsize particles (TAMP) into a cationic guar gum (CG) matrix is reported. Combining antioxidant/photothermal properties of TAMP and mechanical support from injectable CG, the formulated TAMP/CG is explored for treating diabetic wounds. Both in vitro and in vivo assays verify that TAMP/CG can protect the cells from ROS-induced oxidative damage, which can also be strengthened by the local photothermal heating (42 °C) triggered by near-infrared light. Overall, this study establishes the paradigm of enhanced diabetic wound healing by mild hyperthermia-assisted ROS scavenging hydrogels.

Architecting polyelectrolyte hydrogels with Cu-assisted polydopamine nanoparticles for photothermal antibacterial therapy.

Polydopamine nanoparticles (PDA NPs) are an appealing biomimetic photothermal agent for photothermal antibacterial treatment because of their long-term safety, excellent photostability, accessible manufacturing, and good biodegradability. However, the low photothermal conversion efficiency (PCE) of PDA NPs requires high-power and long-term near-infrared light irradiation, which severely restricts their practical application. In this work, PDA@Cu NPs were fabricated by growing Cu NPs in situ on the surface of PDA and then introduced into a polyelectrolyte hydrogel precursor (cationic polyethyleneimine/anionic pectin, named as CPAP). The formulated photothermal platform possessed a high PCE (55.4%), almost twice as much as pure PDA NPs (30.8%). Moreover, the designed CPAP/PDA@Cu captured and killed some bacteria by electrostatic adsorption, which helped enhance the antibacterial performance. As expected, the formed CPAP/PDA@Cu that combined the advantageous features of PDA@Cu NPs (high PCE) and CPAP matrix (inherent antibacterial activity and preventing NPs aggregation) can efficiently kill bacteria both in vitro and in vivo under the help of near-infrared laser irradiation. Taken together, this study offers a promising strategy for constructing a facile and safe PDA-based photothermal agent for photothermal antibacterial therapy.

Engineering Robust Ag-Decorated Polydopamine Nano-Photothermal Platforms to Combat Bacterial Infection and Prompt Wound Healing.

Polydopamine (PDA) nanoparticles have emerged as an attractive biomimetic photothermal agent in photothermal antibacterial therapy due to their ease of synthesis, good biodegradability, long-term safety, and excellent photostability. However, the therapeutic effects of PDA nanoparticles are generally limited by the low photothermal conversion efficiency (PCE). Herein, PDA@Ag nanoparticles are synthesized via growing Ag on the surface of PDA nanoparticles and then encapsulated into a cationic guar gum (CG) hydrogel network. The optimized CG/PDA@Ag platform exhibits a high PCE (38.2%), which is more than two times higher than that of pure PDA (16.6%). More importantly, the formulated CG/PDA@Ag hydrogel with many active groups can capture and kill bacteria through effective interactions between hydrogel and bacteria, thereby benefiting the antibacterial effect. As anticipated, the designed CG/PDA@Ag system combined the advantages of PDA@Ag nanoparticles (high PCE) and hydrogel (preventing aggregation of PDA@Ag nanoparticles and possessing inherent antibacterial ability) is demonstrated to have superior antibacterial efficacy both in vitro and in vivo. This study develops a facile approach to boost the PCE of PDA for photothermal antibacterial therapy, providing a significant step forward in advancing the application of PDA nano-photothermal agents.

Dendritic Hydrogels with Robust Inherent Antibacterial Properties for Promoting Bacteria-Infected Wound Healing.

Bacterial infections are a common problem associated with wound treatment that imposes a significant burden on healthcare systems and patients. As a result, healthcare providers urgently need new treatment strategies to protect people. Hydrogel biomaterials with inherent antimicrobial properties offer an attractive and viable solution to this issue. Here, for the first time, we have developed a new efficient synthetic strategy to prepare cationic hydrogels (PHCI) with intrinsically efficient antimicrobial properties by chemically cross-linking trans-1,4-cyclohexanediamine with 1,3-dibromo-2-propanol using a condensation reaction without the use of toxic cross-linking agents. As expected, the prepared PHCI hydrogel possessed an inherent antibacterial ability that can adsorb and kill Staphylococcus aureus and Escherichia coli electrostatically. Notably, in vivo experiments on normal and diabetic rat models confirmed that the PHCI hydrogel can quickly stop bleeding, efficiently kill bacteria, promote the conversion of macrophages from the proinflammatory M1 phenotype to the repaired M2 phenotype, and accelerate collagen deposition and blood vessel formation, thereby achieving rapid wound healing. Overall, this work presents an effective antibacterial dressing that might provide a facile but effective approach for clinical wound management.

Quantum algorithmic measurement.

There has been recent promising experimental and theoretical evidence that quantum computational tools might enhance the precision and efficiency of physical experiments. However, a systematic treatment and comprehensive framework are missing. Here we initiate the systematic study of experimental quantum physics from the perspective of computational complexity. To this end, we define the framework of quantum algorithmic measurements (QUALMs), a hybrid of black box quantum algorithms and interactive protocols. We use the QUALM framework to study two important experimental problems in quantum many-body physics: determining whether a system's Hamiltonian is time-independent or time-dependent, and determining the symmetry class of the dynamics of the system. We study abstractions of these problems and show for both cases that if the experimentalist can use her experimental samples coherently (in both space and time), a provable exponential speedup is achieved compared to the standard situation in which each experimental sample is accessed separately. Our work suggests that quantum computers can provide a new type of exponential advantage: exponential savings in resources in quantum experiments.

Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing Evaluations.

Wound dressings based on nanomaterials play a crucial role in wound treatment and are widely used in a whole range of medical settings, from minor to life-threatening tissue injuries. This article presents an educational review on the accumulating knowledge in this multidisciplinary area to lay out the challenges and opportunities that lie ahead and ignite the further and faster development of clinically valuable technologies. The review analyzes the functional advantages of nanomaterial-based gauzes and hydrogels as well as hybrid structures thereof. On this basis, the review presents state-of-the-art advances to transfer the (semi)blind approaches to the evaluation of a wound state to smart wound dressings that enable real-time monitoring and diagnostic functions that could help in wound evaluation during healing. This review explores the translation of nanomaterial-based wound dressings and related medical aspects into real-world use. The ongoing challenges and future opportunities associated with nanomaterial-based wound dressings and related clinical decisions are presented and reviewed.

UV-assisted ultrafast construction of robust Fe3O4/polydopamine/Ag Fenton-like catalysts for highly efficient micropollutant decomposition.

Fenton-like catalysts represent a family of promising materials to degrade micropollutants from contaminated water. However, the practical applications of Fenton-like catalysts are mainly limited by low catalytic degradation efficiency and stability. Herein, for the first time, rapid fabrication of Ag-decorated Fe3O4/polydopamine (FPA) microspheres was achieved via the help of UV irradiation, and the designed FPA microspheres were employed as Fenton-like catalysts to degrade micropollutants. Results showed that UV irradiation could activate the generation of the polydopamine shell and accelerate the Ag deposition, which played a crucial role in the rapid synthesis of highly active and stable FPA catalysts. Relative to reported catalysts, these FPA microspheres exhibited outstanding catalytic degradation performance, achieving 94.38% removal of tetracycline within 60 min. This work will provide a convenient strategy in the sustainable and efficient purification of wastewater to improve the quality of human life.

Telmisartan relieves liver fibrosis and portal hypertension by improving vascular remodeling and sinusoidal dysfunction.

BACKGROUNDS: Telmisartan(TEL) has demonstrated anti-fibrotic and blood pressure lowering effect in various diseases. In this study, we aimed to explore the beneficial effects of TEL on portal hypertension(PHT). METHODS: Two models of cirrhosis-induced PHT were involved including carbon tetrachloride injection(CCl4) and bile duct ligation(BDL). Rats were orally gavaged with TEL for 4 weeks. After that, the portal pressure(PP) was determined, and liver and mesenteric tissue specimens were collected to evaluate inflammatory response, liver fibrosis, vascular remodeling, angiogenesis, etc. RESULTS: In CCl4 PHT models, TEL decreased PP significantly from 12.79 ± 2.92 to 6.91 ± 1.19 mmHg(p < 0.05). In inflammatory response, hepatic expressions of interleukin(IL)-6, lipopolysaccharide(LPS), and tumor necrosis factor-α(TNF-α) were significantly decreased after TEL treatment. Moreover, in the liver fibrotic area, the expressions of α-smooth muscle actin(α-SMA), collagen1a1(Col1a1), desmin, transforming growth factor-ß(TGF-ß), and hydroxyproline, and serum hyaluronic acid were significantly decreased after TEL treatment. Additionally, the expressions of von Willebrand factor(vWF), vascular endothelial growth factor(VEGF) and platelet-derived growth factor-ß(PDGF-ß), matrix metallopeptidase(MMP)-2, and MMP-9 were ameliorated in liver sinusoid, while the expressions of MMP-2 and vWF were reduced in mesenteric arteries after TEL treatment. Meanwhile, TEL treatment up-regulated the hepatic expressions of an anti-fibrotic factor Krüppel-like factor-4(KLF-4) and its downstream endothelial nitric oxide synthase(eNOS) in rats with PHT. The performance of TEL in BDL model was similar but slightly weaker. CONCLUSIONS: TEL ameliorated the cirrhosis-induced PHT by reducing liver fibrosis, inflammation responses, angiogenesis, and vascular remodeling. Collectively, KLF-4 and eNOS were the possible molecular targets for the management of cirrhosis-associated PHT.

Facile formation of injectable quaternized chitosan/tannic acid hydrogels with antibacterial and ROS scavenging capabilities for diabetic wound healing.

The wound healing process of the diabetic wound is often hindered by excessive oxygen free radicals and infection. An ideal wound dressing should possess great reactive oxygen species (ROS) scavenging property and considerable antibacterial ability. In this study, we facilely constructed a novel hydrogel dressing with excellent ROS scavenging property and outstanding antibacterial performance by introducing tannic acid (TA) into quaternized chitosan (QCS) matrix. Attributing to the suitable physical crosslinking between TA and QCS, this QCS/TA hydrogel was endowed with injectable and self-healing properties, which could avoid the various external squeezing on the irregular shape by wound dressing. The results showed that it could promote coagulation, suppress inflammation and expedite collagen deposition in the skin defect model of diabetic rats. This study provides a facile and convenient method for constructing injectable hydrogel dressing, which has application potentials in the clinical management of diabetic wounds.

Accuracy of Newer Generation IOL Power Calculation Formulas in Eyes With High Axial Myopia.

PURPOSE: To compare the accuracy of the Barrett Universal II, Emmetropia Verifying Optical (EVO), Haigis, Kane, and SRK/T formulas for intraocular lens power calculation in patients with high axial myopia. METHODS: In this retrospective study, 175 eyes (175 patients) that underwent uneventful cataract surgery were enrolled. According to the axial length (AL), the eyes were divided into long AL (26 ⩽ AL < 28 mm), super long AL (28 ⩽ AL < 30 mm), and extremely long AL (⩾ 30 mm). The mean absolute prediction errors (MAE) 3 months postoperatively and the percentage of eyes within different prediction error were compared, followed by subgroup analysis. RESULTS: The MAE and percentage of eyes within ±0.50 diopters (D) of the five formulas were as follows: Barrett Universal II (0.342, 74.9%), EVO 2.0 (0.314, 82.3%), Haigis (0.336, 74.9%), Kane (0.318, 78.9%), and SRK/T (0.398, 69.7%) (P = .552 and .071, respectively). Although no significant difference was found among the five formulas in the super and extremely long AL groups (P = .792 and .227, respectively), the EVO 2.0 formula achieved the highest accuracy (88.9%, 72 of 81) in the long AL group (P = .049). Moreover, the accuracy of the EVO 2.0 and Haigis formulas was stable, regardless of AL. The SRK/T formula showed a negative trend in the long and super long AL groups, whereas the Barrett Universal II, Kane, and SRK/T formulas showed positive trends in the extremely long AL group. CONCLUSIONS: Overall, the EVO 2.0 and Kane formulas achieved better results in patients with high axial myopia, whereas the other three formulas showed slightly poor outcomes. [J Refract Surg. 2021;37(11):754-758.].

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection.

BACKGROUND: Multiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients' prognosis. METHODS: A total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People's Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients' survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM). RESULTS: Patients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40-2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39-2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716-0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25-2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20-2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses. CONCLUSION: In a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC.

BACKGROUND: The gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) ratio has been reported as an effective predictor of the severity of hepatitis and HCC. The purpose of this study was to determine the role of the GGT/ALT ratio in the prediction of vascular invasion and survival outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The risk factors for vascular invasion were determined by univariate/multivariate logistic analysis. The cut-off value of GGT/ALT in predicting vascular invasion was calculated using the receiver operating characteristic (ROC) curve. The prognostic value of GGT/ALT was examined by Cox analysis and Kaplan-Meier curves. Sensitivity analysis, such as subgroup analysis and propensity score matching (PSM), was performed to reduce potential confounding bias. RESULTS: A high GGT/ALT ratio was identified as an independent risk factor for vascular invasion (P = 0.03). The correlation analysis suggested that higher GGT/ALT was associated with more severe tumour burdens, including vascular invasion (P < 0.001), tumour volume > 5 cm (P < 0.001), poor pathological differentiation (P = 0.042), more severe BCLC (P < 0.001) and ALBI grade (P = 0.007). In the survival analysis, a high GGT/ALT ratio was associated with poor overall survival (OS) (HR: 1.38; 95% CI 1.03, 1.87; P < 0.0001) and disease-free survival (DFS) (HR: 1.32; 95% CI 1.03, 1.87; P < 0.0001). In the subgroup analysis, similar results were consistently observed across most subgroups. In PSM analysis, GGT/ALT remained independently associated with vascular invasion (OR, 186; 95% CI 1.23, 3.33). CONCLUSION: The GGT/ALT ratio was a potential effective factor in the prediction of vascular invasion and prognosis in patients with HBV-related HCC.

A near-infrared fluorescent probe for highly specific and ultrasensitive detection of hypochlorite ions in living cells.

Hypochlorite (ClO-) is an important reactive oxygen species (ROS) in organisms. In this work, a fluorescent probe DBTM based on triphenylamine was synthesized successfully and characterized by spectral methods. The designed probe can rapidly respond to ClO- in just 1 min, followed by the apparent color change from red to yellow. The colorimetric and ratiometric absorbance change of DBTM was attributed to the strong oxidation of ClO-, which broke the connected double bonds and destroyed the conjugate system. The probe DBTM showed an excellent selectivity towards ClO- in comparison with other ROS probes. Besides, the DBTM probe exhibited a highly sensitive response to ClO-, with the detection limits calculated to be 3.3 nM. The probe can be applied in the form of cotton swabs and test strips that could detect ClO- easily, suggesting its potential use as imaging agents for realistic ClO- detection. In particular, DBTM exhibited very low background fluorescence in living cells and was able to detect the minor variation of endogenous hypochlorite in L929 cells. Based on these advantages, the probe DBTM could be a good candidate for detecting ClO- in biological systems.

Highly efficient removal of antibiotic from biomedical wastewater using Fenton-like catalyst magnetic pullulan hydrogels.

Magnetic nanoparticles that can be employed as Fenton-like catalysts Fenton-like catalysts are attractive materials for degrading antibiotics. In this study, we facilely prepared novel magnetic pullulan (MP) hydrogels by doping modified magnetic nanoparticles into pullulan matrices, which could enhance catalytic degradation performance and strengthen the stability of resulting hydrogels. This is the first time that MP hydrogels have been fabricated successfully and used as Fenton-like catalysts for tetracycline hydrochloride (TCH) degradation. MP hydrogels were characterized and their catalytic TCH degradation abilities were also investigated. The optimized conditions (pH value, Fe3O4 content, H2O2 content and TCH concentration) for TCH degradation were investigated. The optimized system showed excellent degradation efficiency for TCH. Further, the degradation mechanism was comprehensively studied. Finally, synthesized MP hydrogels showed impressive reusability and stability in the cycle experiment. Thus, our findings would open new possibilities to develop magnetic hydrogels in eliminating antibiotic contaminants.

ε­Polylysine-stabilized agarose/polydopamine hydrogel dressings with robust photothermal property for wound healing.

Polydopamine (PDA) is emerging as an attractive photothermal agent due to its good photothermal performance and excellent biocompatibility. However, without chemical modification, PDA is normally unstable and usually leached out from the constructed biomaterials, realistically limiting its application space. Here, we constructed a new hydrogel dressing with robust and stable photothermal performance by introduction of ε-Polylysine (ε-PL) into agarose/PDA matrix to efficiently lock PDA. By optimizing PDA/ε-PL rational dose in agarose network structure, a hybrid agarose/PDA/ε-PL hydrogel (ADPH) with stable photothermal functionality and desirable physicochemical properties could be achieved. ADPH possessed satisfactory microbicidal efficacy in vivo, which enabled the bacteria-infected skin wound to be cured quickly by successful suppressing inflammation, accelerating collagen deposition and promoting angiogenesis in a bacterial-infected wound model. Collectively, this study illustrates a simple, convenient but powerful strategy to design functionally stable ADPH dressing for treating dermal wounds, which could open vistas in clinical wound management.

Polydopamine nanoparticle-dotted food gum hydrogel with excellent antibacterial activity and rapid shape adaptability for accelerated bacteria-infected wound healing.

Most commonly used wound dressings have severe problems, such as an inability to adapt to wound shape or a lack of antibacterial capacity, affecting their ability to meet the requirements of clinical applications. Here, a nanocomposite hydrogel (XKP) is developed by introducing polydopamine nanoparticles (PDA NPs) into a food gum matrix (XK, consisting of xanthan gum and konjac glucomannan, both FDA-approved food thickening agents) for skin wound healing. In this system, the embedded PDA NPs not only interact with the food gum matrix to form a hydrogel with excellent mechanical strength, but also act as photothermal transduction agents to convert near-infrared laser radiation to heat, thereby triggering bacterial death. Moreover, the XKP hydrogel has high elasticity and tunable water content, enabling it to adapt to the shape of the wound and insulate it, providing a moist environment suitable for healing. In-vivo skin wound healing results clearly demonstrate that XKP can significantly accelerate the healing of wounds by reducing the inflammatory response and promoting vascular reconstruction. In summary, this strategy provides a simple and practical method to overcome the drawbacks of traditional wound dressings, and provides further options when choosing suitable wound healing materials for clinical applications.

COX-2/sEH Dual Inhibitor PTUPB Alleviates CCl 4 -Induced Liver Fibrosis and Portal Hypertension.

Background: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl) -benzenesulfonamide (PTUPB), a dual cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) inhibitor, was found to alleviate renal, pulmonary fibrosis and liver injury. However, few is known about the effect of PTUPB on liver cirrhosis. In this study, we aimed to explore the role of PTUPB in liver cirrhosis and portal hypertension (PHT). Method: Rat liver cirrhosis model was established via subcutaneous injection of carbon tetrachloride (CCl4) for 16 weeks. The experimental group received oral administration of PTUPB (10 mg/kg) for 4 weeks. We subsequently analyzed portal pressure (PP), liver fibrosis, inflammation, angiogenesis, and intra- or extrahepatic vascular remodeling. Additionally, network pharmacology was used to investigate the possible mechanisms of PTUPB in live fibrosis. Results: CCl4 exposure induced liver fibrosis, inflammation, angiogenesis, vascular remodeling and PHT, and PTUPB alleviated these changes. PTUPB decreased PP from 17.50 ± 4.65 to 6.37 ± 1.40 mmHg, reduced collagen deposition and profibrotic factor. PTUPB alleviated the inflammation and bile duct proliferation, as indicated by decrease in serum interleukin-6 (IL-6), liver cytokeratin 19 (CK-19), transaminase, and macrophage infiltration. PTUPB also restored vessel wall thickness of superior mesenteric arteries (SMA) and inhibited intra- or extrahepatic angiogenesis and vascular remodeling via vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), etc. Moreover, PTUPB induced sinusoidal vasodilation by upregulating endothelial nitric oxide synthase (eNOS) and GTP-cyclohydrolase 1 (GCH1). In enrichment analysis, PTUPB engaged in multiple biological functions related to cirrhosis, including blood pressure, tissue remodeling, immunological inflammation, macrophage activation, and fibroblast proliferation. Additionally, PTUPB suppressed hepatic expression of sEH, COX-2, and transforming growth factor-ß (TGF-ß). Conclusion: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)- benzenesulfonamide ameliorated liver fibrosis and PHT by inhibiting fibrotic deposition, inflammation, angiogenesis, sinusoidal, and SMA remodeling. The molecular mechanism may be mediated via the downregulation of the sEH/COX-2/TGF-ß.