Parameter identification of Johnson-Cook constitutive model based on genetic algorithm and simulation analysis for 304 stainless steel.

Addressing the significant discrepancy between actual experimental cutting force and its predicted values derived from traditional constitutive model parameter identification methods, a reverse identification research of the Johnson-Cook (J-C) constitutive model for 304 stainless steel was conducted via genetic algorithm. Considering actual cutting zone and the influence of feed motion on the rake (flank) angle, an unequal division shear zone model was established to implement the theoretical calculation for shear zone stress. Through cutting experiments, the spindle speed was negatively correlated with the cutting force at first, and then became positively correlated; The empirical formula (EXP model) for turning force was corrected, revealing that the EXP model was unable to provide optimal predicted values for cutting force. The influence of the J-C constitutive parameter C on the cutting morphology was firstly investigated through simulation analysis, and determined an appropriate value for C, then obtained the precise values for the other four constitutive parameters by genetic algorithm. Moreover, the simulated values of cutting force in JC1 model (obtained from the Split Hopkinson Pressure Bar test) and JCM model (the improved model using genetic algorithm) were obtained by three-dimensional (3-D) simulation via FEM software. The results indicated that, the maximum error between actual experimental cutting force and its simulated values (by JCM model) was 14.8%, with an average error of 6.38%. These results outperformed the JC1 and EXP models, suggesting that the JCM model identified via genetic algorithm was more reliable.

Study on the mechanism of hepatotoxicity of Aucklandiae radix through liver metabolomics and network pharmacology.

Background: Aucklandiae Radix (CAR) and its roasted processed products (PAR) are extensively used in various Chinese patent medicines due to their diverse pharmacological activities. However, numerous side effects of CAR have been reported and the hepatotoxicity and the corresponding mechanisms have not been thoroughly investigated. Our study aims to explore the underlying mechanism of the hepatotoxic impacts of CAR. Methods: In this study, metabolomic analysis was performed using liver tissue from the mice administered with different dosages of CAR/PAR extracts to examine the hepatotoxic impacts of CAR and elucidate the underlying mechanism. Network pharmacology was employed to predict the potential molecular targets and associated signaling pathways based on the distinctive compounds between CAR and PAR. A composition-target-GO-Bio process-metabolic pathway network was constructed by integrating the hepatotoxicity-related metabolic pathways. Finally, the target proteins related with the hepatotoxic effect of CAR were identified and validated in vivo. Results: The metabolomics analysis revealed that 33 related metabolic pathways were significantly altered in the high-dose CAR group, four of which were associated with the hepatotoxicity and could be alleviated by PAR. The network identified NQO1 as the primary target of the hepatotoxic effect induced by CAR exposure, which was subsequently verified by Western Blotting. Further evidence in vivo demonstrated that Nrf2 and HO-1, closely related to NQO1, were also the main targets through which CAR induced the liver injury, and that oxidative stress should be the primary mechanism for the CAR-induced hepatotoxicity. Conclusions: This preliminary study on the hepatic toxic injury of CAR provides a theoretical basis for the rational and safe use of CAR rationally and safely in clinical settings.

Comparing oxygen therapies for hypoxemia prevention during gastrointestinal endoscopy under procedural sedation: A systematic review and network meta-analysis.

STUDY OBJECTIVE: Hypoxemia is the most frequent adverse event observed during gastrointestinal endoscopy under procedural sedation. An optimum oxygen therapy has still not been conclusively determined. DESIGN: A systematic review and network meta-analysis of randomized clinical trials. SETTING: Digestive Endoscopy Center. PATIENTS: Adults (≥18 years old and of both sexes) during gastrointestinal endoscopy under procedural sedation. INTERVENTIONS: Pubmed, MEDLINE, Web of Science, Embase, and Clinicaltrials.gov. were searched until June 30, 2023. Randomized clinical trials (RCTs) comparing any oxygen therapy with another oxygen therapy or with placebo (nasal cannula, NC) were included. MEASUREMENT: The primary outcome was the incidence of hypoxemia, defined as the pulse oxygen saturation (SpO2). Random-effects network meta-analyses were performed. Data are reported as odds ratios (OR), prediction intervals (PrI) and 95% CI. Bias risk was evaluated following the guidelines outlined by the Cochrane Collaboration. The quality of evidence was evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: We included 27 RCTs with a total of 7552 patients. Compared to the use of NC, non-invasive positive pressure ventilation (NIPPV) demonstrated superior efficacy in mitigating hypoxemia (NIPPV vs. NC, OR = 0.16, 95% CI: 0.08-0.31, 95% PrI: 0.06-0.41), followed by Wei nasal jet tube (WNJT) (WNJT vs. NC, OR = 0.17, 95% CI: 0.10-0.30, 95% PrI: 0.07-0.42). The efficacy for preventing hypoxemia was ranked as follows: NIPPV > WNJT > oropharynx/nasopharyngeal catheter > high-flow nasal oxygenation > nasal mask > NC. CONCLUSIONS: During gastrointestinal endoscopy under procedural sedation, all other advanced oxygen therapies were found to be more efficacious than nasal cannula. NIPPV and WNJT appear to be the most efficacious oxygen therapy for preventing hypoxemia. Additionally, clinicians should make a choice regarding the most suitable oxygen therapy based on the risk population, type of endoscopy and adverse events.

Twin Boundaries-Induced Centrosymmetric Breaking of Hollow CaTiO3 Nanocuboids for Piezocatalytic Hydrogen Evolution.

Piezocatalysis, a transformative mechanochemical energy conversion technique, has received considerable attention over the past decade for its role in processes such as hydrogen evolution from water. Despite notable progress in the field, challenges remain, particularly in the areas of limited piezocatalysis efficiency and limited availability of materials requiring a non-centrosymmetric structure. Here, a pioneering contribution is presented by elucidating the piezocatalytic properties of hollow CaTiO3 nanocuboids, a centrosymmetric material with a nominally nonpolar state. Remarkably, CaTiO3 nanocuboids exhibit an impressive hydrogen production rate of 3.44 mmol g-1 h-1 under ultrasonic vibrations, surpassing the performance of the well-established piezocatalyst BaTiO3 (2.23 mmol g-1 h-1). In contrast, commercial CaTiO3 nanoparticles do not exhibit piezocatalytic performance. The exceptional performance of hollow CaTiO3 nanocuboids is attributed to the abundance presence of twin boundaries on the {110} facet within its crystal structure, which can impart significant polarization strength to CaTiO3. Extending the investigation to other centrosymmetric materials, such as SrZrO3 and BaZrO3, the experimental results also demonstrate their commendable properties for piezocatalytic hydrogen production from water. This research underscores the significant potential of centrosymmetric materials in piezocatalysis.

Fructus Jujubae cooperated with water-expelling members in Shizao decoction alleviated intestinal injury and malignant ascites by modulating gut microbiota and metabolic homeostasis.

BACKGROUND: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown. PURPOSE: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function. METHODS: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes. RESULTS: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid. CONCLUSION: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.

Sucralose triggers insulin resistance leading to follicular dysplasia in mice.

Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.

Calcium Single Atom Confined in Nitrogen-Doped Carbon-Coupled Polyvinylidene Fluoride Membrane for High-Performance Piezocatalysis.

A piezoelectric polymer membrane based on single metal atoms was demonstrated to be effective by anchoring isolated calcium (Ca) atoms on a composite of nitrogen-doped carbon and polyvinylidene fluoride (PVDF). The addition of Ca-atom-anchored carbon nanoparticles not only promotes the formation of the ß phase (from 29.8 to 56.3%), the most piezoelectrically active phase, in PVDF, but also introduces much higher porosity and hydrophilicity. Under ultrasonic excitation, the fabricated catalyst membrane demonstrates a record-high and stable dye decomposing rate of 0.11 min-1 and antibacterial efficiencies of 99.8%. Density functional theory calculations reveal that the primary contribution to catalytic activity arises from single-atom Ca doping and that a possible synergistic effect between PVDF and Ca atoms can improve the catalytic performance. It is shown that O2 molecules can be easily hydrogenated to produce ·OH on Ca-PVDF, and the local electric field provided by the ß-phase-PVDF might enhance the production of ·O2-. The proposed polymer membrane is expected to inspire the rational design of piezocatalysts and pave the way for the application of piezocatalysis technology for practical environmental remediation.

Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Multi-omics analysis of kidney, bone and bone marrow explored potential mechanisms of Erzhi Wan against osteoporosis with kidney-Yin deficiency.

Osteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.

Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.

Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis Fisch.) in attenuating Doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. AIM OF THE STUDY: To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. MATERIALS AND METHODS: UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. RESULTS: Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. CONCLUSION: Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer.

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide and a major public issue affecting the health of people. Therefore, it is essential to explore effective drugs for the treatment of DN. In this study, the traditional Chinese medicine (TCM) formula, Zhijun Tangshen Decoction (ZJTSD), a prescription modified from the classical formula Didang Decoction, has been used in the clinical treatment of DN. However, the chemical basis underlying the therapeutic effects of ZJTSD in treating DN remains unknown. In this study, compounds of ZJTSD and serum after oral administration in rats were identified and analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Meanwhile, a semi-quantitative approach was used to analyze the dynamic changes in the compounds of ZJTSD in vivo. UPLC-Q/TOF-MS analysis identified 190 compounds from ZJTSD, including flavonoids, anthraquinones, terpenoids, phenylpropanoids, alkaloids, and other categories. A total of 156 xenobiotics and metabolites, i.e., 51 prototype compounds and 105 metabolites, were identified from the compounds absorbed into the blood of rats treated with ZJTSD. The results further showed that 23 substances with high relative content, long retention time, and favorable pharmacokinetic characteristics in vivo deserved further investigations and validations of bioactivities. In conclusion, this study revealed the chemical basis underlying the complexity of ZJTSD and investigated the metabolite profiling and pharmacokinetics of ZJTSD-related xenobiotics in rats, thus providing a foundation for further investigation into the pharmacodynamic substance basis and metabolic regulations of ZJTSD.

Distinguishment of different varieties of rhubarb based on UPLC fingerprints and chemometrics.

Rhubarb, a widely used traditional Chinese medicine (TCM), is primarily used for purging in practice. It is derived from the dried roots and rhizomes of R. tanguticum Maxim. ex Balf. (RT), Rheum officinale Baill. (RO) and R. palmatum L. (RP). To date, although the three varieties of rhubarb have been used as the same medicine in clinical, studies have found that they have different chemical compositions and pharmacological effects. To ensure the stability of rhubarb for clinical use, a simple and effective method should be built to compare and discriminate three varieties of rhubarb. Here, ultra-performance liquid chromatography-diode array detection (UPLC-DAD) fingerprints combined with chemometric methods were developed to evaluate and discriminate 29 batches of rhubarb. Similarity evaluation, hierarchical cluster analysis (HCA) and principal component analysis (PCA) showed that the chemical constituents of the three varieties of rhubarb were significantly different, and the three varieties could be effectively distinguished. Finally, all the 14 common peaks were identified by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In this research, the developed UPLC fingerprints offer a simple, reliable and specific approach for distinguishing different varieties of rhubarb. This research aims to promote the scientific and appropriate clinical application of rhubarb from three varieties.

Recent Advances in Topical Hemostatic Materials.

Untimely or improper treatment of traumatic bleeding may cause secondary injuries and even death. The traditional hemostatic modes can no longer meet requirements of coping with complicated bleeding emergencies. With scientific and technological advancements, a variety of topical hemostatic materials have been investigated involving inorganic, biological, polysaccharide, and carbon-based hemostatic materials. These materials have their respective merits and defects. In this work, the application and mechanism of the major hemostatic materials, especially some hemostatic nanomaterials with excellent adhesion, good biocompatibility, low toxicity, and high adsorption capacity, are summarized. In the future, it is the prospect to develop multifunctional hemostatic materials with hemostasis and antibacterial and anti-inflammatory properties for promoting wound healing.

High-performance bismuth vanadate photoanodes cocatalyzed with nitrogen, sulphur co-doped ferrocobalt-metal organic frameworks thin layer for photoelectrochemical water splitting.

In this study, we prepare a highly efficient BiVO4 photoanode co-catalyzed with an ultrathin layer of N, S co-doped FeCo-Metal Organic Frameworks (MOFs) for photoelectrochemical water splitting. The introduction of N and S into FeCo-MOFs enhances electron and mass transfer, exposing more catalytic active sites and significantly improving the catalytic performance of N, S co-doped FeCo-based MOFs in water oxidation. The optimized BiVO4/NS-FeCo-MOFs photoanode exhibits impressive results, with a photocurrent density of 5.23 mA cm-2 at 1.23 V vs. Reversible Hydrogen Electrode (RHE) and an incident photon-to-charge conversion efficiency (IPCE) of 74.4 % at 450 nm in a 0.1 M phosphate buffered solution (pH = 7). These values are 4.84 times and 6.2 times higher than those of the original BiVO4 photoanode, respectively. Furthermore, the optimized BiVO4/NS-FeCo-MOFs photoanode demonstrates exceptional long-term stability, maintaining 96 % of the initial current after five hours.

Near-infrared light-activatable, analgesic nanocomposite delivery system for comprehensive therapy of diabetic wounds in rats.

Impaired angiogenesis, bacterial infection, persistent severe pain, exacerbated inflammation, and oxidative stress injury are intractable problems in the treatment of chronic diabetic ulcer wounds. A strategy that effectively targets all these issues has proven challenging. Herein, an in-situ sprayable nanoparticle-gel composite comprising platinum clusters (Pt) loaded-mesoporous polydopamine (MPDA) nanoparticle and QX-314-loaded fibrin gel (Pt@MPDA/QX314@Fibrin) was developed for diabetic wound analgesia and therapy. The composite shows good local analgesic effect of QX-314 mediated by near-infrared light (NIR) activation of transient receptor potential vanilloid 1 (TRPV1) channel, as well as multifunctional therapeutic effects of rapid hemostasis, anti-inflammation, antioxidation, and antibacterial properties that benefit the fast-healing of diabetic wounds. Furthermore, it demonstrates that the composite, with good biodegradability and biosafety, significantly relieved wound pain by inhibiting the expression of c-Fos in the dorsal root ganglion and the activation of glial cells in the spinal cord dorsal horn. Consequently, our designed sprayable Pt@MPDA/QX314@Fibrin composite with good biocompatibility, NIR activation of TRPV1 channel-mediated QX-314 local wound analgesia and comprehensive treatments, is promising for chronic diabetic wound therapy.

Cardiac computed tomography angiography for assessment of endothelial insufficiency of left atrial appendage disc-like occluder.

INTRODUCTION: This study was performed to explore the diagnostic value of cardiac computed tomography angiography (CCTA) for endothelial insufficiency (EIS) of a left atrial appendage (LAA) disc-like occluder. METHODS: Fifty-nine patients with nonvalvular atrial fibrillation who underwent placement of an LAA disc-like occluder (LAmbre; Lifetech Scientific) in our hospital were retrospectively analyzed. Patients who were found to have contrast agent entering the LAA at the 3-month postoperative CCTA examination underwent Hounsfield unit (HU) measurement of the LAA and construction of a three-dimensional (3D) model of the device for preliminary discernment between peri-device leakage (PDL) and EIS. These patients were then further examined by transesophageal echocardiography (TEE) to check for concordance with the computed tomography (CT) findings. According to the CT and TEE results, all patients were divided into the PDL group, total endothelialization group, and EIS group. The endothelial conditions and other implantation-related results were also tracked at the 6-month follow-up. RESULTS: All 59 patients underwent successful implantation of the LAmbre LAA closure device with no severe adverse events during the procedure. Thirty-five patients were found to have contrast agent entering the LAA at the 3-month postoperative CCTA follow-up. Based on the CT HU measurement and the 3D construction analysis results, these 35 patients were divided into the PDL group (19 patients) and the EIS group (16 patients). In the PDL group, the contrast agent infiltrated from the shoulder along the periphery of the occluder on two-dimensional (2D) CT images, and the 3D model showed a gap between the LAA and the device cover. However, the CCTA images of the other 16 patients in the EIS group showed that the contrast agent in the occluder on the 2D CTA images and 3D construction model confirmed the absence of a gap between the LAA and the device cover. TEE confirmed all of the CT results. The 6-month follow-up results showed that 14 of 19 patients in the EIS group achieved total endothelialization, whereas this number in the PDL group was only five of 19 patients. CONCLUSION: CCTA can replace TEE for examination of the endothelialization status, and patients with EIS have a higher chance of endothelialization than patients with PDL.

Leech extract alleviates idiopathic pulmonary fibrosis by TGF-ß1/Smad3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. AIM OF THE STUDY: Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. MATERIALS AND METHODS: In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-ß1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. RESULTS: Using TGF-ß1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. CONCLUSIONS: Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-ß1/Smad3 signaling pathway.