Dietary supplementation of pterostilbene, a major component in small berries, prevents alcohol-induced liver injury associated with lipid accumulation and inflammation.

Pterostilbene (PTE), a natural stilbene found in small berries, exhibits multiple pharmacological activities, particularly antioxidant and anti-inflammatory activities. This study explores the dietary supplementation of PTE to ameliorate acute and chronic alcohol-associated liver disease (ALD). C57BL/6 mice were administrated with PTE and subjected to acute or chronic alcohol stimulation. They were intragastrically administered with alcohol (5 g kg-1, 3 times per 24 h) to induce acute alcohol liver injury or fed a Lieber-DeCarli liquid diet containing 5% ethanol for 4 weeks and a single binge to induce chronic alcoholic liver injury. In the acute ethanol model, PTE decreased the serum transaminase and triglyceride (TG) levels and ameliorated lipid droplet accumulation. PTE ameliorated acute ethanol-induced hepatic steatosis by inhibiting the expression of SREBP1 and its target genes and up-regulating PPARα expression. PTE could reverse the inflammatory response by inhibiting NLRP3 activation, inflammatory factor secretion, and macrophage recruitment caused by acute ethanol exposure. PTE could synergistically activate the SIRT1-AMPK and LXR/FXR axis in mice with acute ethanol exposure. In the chronic-binge ethanol feeding model, PTE also decreased serum transaminase and TG levels and ameliorated hepatocellular ballooning, macrovesicular steatosis, lipid accumulation and inflammation. Chronic-binge ethanol feeding could induce extracellular matrix dysfunction with an increase in α-SMA, collagen I and TIMP-1 expression, which was decreased by PTE. PTE increased SIRT1 expression and AMPK phosphorylation and activated the LXRs/FXR axis, which could be reduced by chronic-binge ethanol feeding. PTE could prevent liver injury caused by alcohol regardless of acute or chronic exposure. These results suggest that PTE can be utilized as a dietary health supplement to avoid ALD and promote health and quality of life.

Astilbin alleviates hepatic fibrosis through PXR-PINK1/Parkin pathway: A new strategy by regulating hepatic stellate cells-macrophage crosstalk.

BACKGROUND: Astilbin (ATB), a natural dihydroflavonol compound, exists in many plants, processed and functional foods. ATB has multiple pharmacological effects, such as antioxidant, lipid-lowering, and hepatoprotective. However, its anti-hepatic fibrosis and mechanisms remain unclearly elucidated. PURPOSE: This study explored the effect of ATB against the hepatic fibrosis and its regulation of hepatic microenvironment by regulating hepatic stellate cells-macrophage crosstalk. METHOD: Thioacetamide (TAA) was intraperitoneal injected to establish hepatic fibrosis mice, and treated with ATB or curcumin by gavage, respectively. Hepatic stellate cells (HSCs) were stimulated with TGF-ß or conditioned medium (CM) from LPS-induced THP-1, then cultured with ATB, PXR agonist or antagonist. RESULTS: In TAA-induced mice, ATB improved histopathological changes, serum transaminases increase; alleviated extracellular matrix (ECM) deposition, epithelial-mesenchymal transformation (EMT), inflammatory infiltration, PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy and activated pregnane X receptor (PXR) expression. In vitro, ATB significantly reduced ECM, inflammatory cytokines release, mitophagy, EMT, and activated PXR expression. ATB could increase PXR and decrease PINK1/Parkin, functioning as a PXR agonist. PXR deficiency in LX-2 could degrade the regulation of ATB on ECM, inflammation, EMT, and mitophagy. CM from LPS-induced THP-1 activated LX-2 and resulted in PXR decreasing, while ATB could regulate the crosstalk between HSCs and macrophages. Deficiency of PXR, whether in LX-2 or in macrophages, all weakened the inhibitory effect of ATB on α-SMA, EMT, inflammatory cytokines, and PINK1/Parkin signaling. CONCLUSION: ATB ameliorated hepatic fibrosis by inhibiting HSCs activation, inflammation and EMT through PXR-mediated PINK1/Parkin signaling. Especially, ATB targeted the hepatic microenvironment between hepatic stellate cells and macrophages, which might be a promising strategy for the treatment of hepatic fibrosis.

Efficient urinary stone type prediction: a novel approach based on self-distillation.

Urolithiasis is a leading urological disorder where accurate preoperative identification of stone types is critical for effective treatment. Deep learning has shown promise in classifying urolithiasis from CT images, yet faces challenges with model size and computational efficiency in real clinical settings. To address these challenges, we developed a non-invasive prediction approach for determining urinary stone types based on CT images. Through the refinement and improvement of the self-distillation architecture, coupled with the incorporation of feature fusion and the Coordinate Attention Module (CAM), we facilitated a more effective and thorough knowledge transfer. This method circumvents the extra computational expenses and performance reduction linked with model compression and removes the reliance on external teacher models, markedly enhancing the efficacy of lightweight models. achieved a classification accuracy of 74.96% on a proprietary dataset, outperforming current techniques. Furthermore, our method demonstrated superior performance and generalizability on two public datasets. This not only validates the effectiveness of our approach in classifying urinary stones but also showcases its potential in other medical image processing tasks. These results further reinforce the feasibility of our model for actual clinical deployment, potentially assisting healthcare professionals in devising more precise treatment plans and reducing patient discomfort.

Targeting STIM1 Contributes to Alleviating Remodeling of Vascular Smooth Muscle Cells in Atherosclerosis.

BACKGROUND: Remodeling of vascular smooth muscle cells (VSMCs), as a pathological hallmark of cardiovascular diseases, is related to the molecular rewiring of Calcium signaling, which induces upregulation of stromal interaction molecule (STIM) proteins. This study analyzed the influence of STIM1 proteins on the remodeling of VSMCs in atherosclerosis (AS). METHODS: After oxidized low-density lipoprotein (ox-LDL) treatment and transfection, VSMC viability, migration, and invasion were separately measured using Cell Counting Kit-8, Scratch assay, and Transwell assay. An animal AS model was constructed, and histological analysis via hematoxylin-eosin staining was conducted on the aorta. RESULTS: Ox-LDL promoted expression of STIM1 and Orai calcium release-activated calcium modulator 1 (Orai1). STIM1 or Orai1 downregulation suppressed viability, migration, invasion, and phenotypic switching of ox-LDL-treated VSMCs, whereas STIM1 or Orai1 upregulation had opposite effects. Orai1 level was upregulated by STIM1 overexpression. Orai1 silencing reversed the effects of STIM1 overexpression in VSMCs. STIM1 deficiency alleviated AS and regulated expression of Orai1 and phenotypic switch-related factors in vivo. CONCLUSION: STIM1 deficiency suppresses viability, migration, invasion, and phenotypic switching of ox-LDL-induced VSMCs and alleviates AS by inhibiting Orai1.

MGPPI: multiscale graph neural networks for explainable protein-protein interaction prediction.

Protein-Protein Interactions (PPIs) involves in various biological processes, which are of significant importance in cancer diagnosis and drug development. Computational based PPI prediction methods are more preferred due to their low cost and high accuracy. However, existing protein structure based methods are insufficient in the extraction of protein structural information. Furthermore, most methods are less interpretable, which hinder their practical application in the biomedical field. In this paper, we propose MGPPI, which is a Multiscale graph convolutional neural network model for PPI prediction. By incorporating multiscale module into the Graph Neural Network (GNN) and constructing multi convolutional layers, MGPPI can effectively capture both local and global protein structure information. For model interpretability, we introduce a novel visual explanation method named Gradient Weighted interaction Activation Mapping (Grad-WAM), which can highlight key binding residue sites. We evaluate the performance of MGPPI by comparing with state-of-the-arts methods on various datasets. Results shows that MGPPI outperforms other methods significantly and exhibits strong generalization capabilities on the multi-species dataset. As a practical case study, we predicted the binding affinity between the spike (S) protein of SARS-COV-2 and the human ACE2 receptor protein, and successfully identified key binding sites with known binding functions. Key binding sites mutation in PPIs can affect cancer patient survival statues. Therefore, we further verified Grad-WAM highlighted residue sites in separating patients survival groups in several different cancer type datasets. According to our results, some of the highlighted residues can be used as biomarkers in predicting patients survival probability. All these results together demonstrate the high accuracy and practical application value of MGPPI. Our method not only addresses the limitations of existing approaches but also can assists researchers in identifying crucial drug targets and help guide personalized cancer treatment.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

GIHP: Graph convolutional neural network based interpretable pan-specific HLA-peptide binding affinity prediction.

Accurately predicting the binding affinities between Human Leukocyte Antigen (HLA) molecules and peptides is a crucial step in understanding the adaptive immune response. This knowledge can have important implications for the development of effective vaccines and the design of targeted immunotherapies. Existing sequence-based methods are insufficient to capture the structure information. Besides, the current methods lack model interpretability, which hinder revealing the key binding amino acids between the two molecules. To address these limitations, we proposed an interpretable graph convolutional neural network (GCNN) based prediction method named GIHP. Considering the size differences between HLA and short peptides, GIHP represent HLA structure as amino acid-level graph while represent peptide SMILE string as atom-level graph. For interpretation, we design a novel visual explanation method, gradient weighted activation mapping (Grad-WAM), for identifying key binding residues. GIHP achieved better prediction accuracy than state-of-the-art methods across various datasets. According to current research findings, key HLA-peptide binding residues mutations directly impact immunotherapy efficacy. Therefore, we verified those highlighted key residues to see whether they can significantly distinguish immunotherapy patient groups. We have verified that the identified functional residues can successfully separate patient survival groups across breast, bladder, and pan-cancer datasets. Results demonstrate that GIHP improves the accuracy and interpretation capabilities of HLA-peptide prediction, and the findings of this study can be used to guide personalized cancer immunotherapy treatment. Codes and datasets are publicly accessible at: https://github.com/sdustSu/GIHP.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1ß levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.

BiVO4 Photoanodes Enhanced with Metal Phosphide Co-Catalysts: Relevant Properties to Boost Photoanode Performance.

Achieving highly performant photoanodes for oxygen evolution is key to developing photoelectrochemical devices for solar water splitting. In this work, BiVO4 photoanodes are enhanced with a series of core-shell structured bimetallic nickel-cobalt phosphides (MPs), and key insights into the role of co-catalysts are provided. The best BiVO4 /Ni1.5 Co0.5 P and BiVO4 /Ni0.5 Co1.5 P photoanodes achieve a 3.5-fold increase in photocurrent compared with bare BiVO4 . It is discovered that this enhanced performance arises from a synergy between work function, catalytic activity, and capacitive ability of the MPs. Distribution of relaxation times analysis reveals that the contact between the MPs, BiVO4 , and the electrolyte gives rise to three routes for hole injection into the electrolyte, all of which are significantly improved by the presence of a second metal cation in the co-catalyst. Kinetic studies demonstrate that the significantly improved interfacial charge injection is due to a lower charge-transfer resistance, enhanced oxygen-evolution reaction kinetics, and larger surface hole concentrations, providing deeper insights into the carrier dynamics in these photoanode/co-catalyst systems for their rational design.

Sesamol as a potential candidate for the treatment of hepatic fibrosis, based on its regulation of FXR/LXR axis-mediated inhibition of autophagy through crosstalk between hepatic cells and macrophage.

BACKGROUND: Sesamol (SEM), a natural lignan compound isolated from sesame, has strong anti-oxidant property, regulating lipid metabolism, decreasing cholesterol and hepatoprotection. However, its anti-hepatic fibrosis effect and mechanisms have not been comprehensively elucidated. HYPOTHESIS/PURPOSE: This study aims to investigate the anti-hepatic fibrosis of SEM and its underlying mechanisms. METHOD: C57BL/6 mice with hepatic fibrosis were induced by TAA, then administrated with SEM or curcumin, respectively. HSCs were stimulated by TGF-ß or conditioned medium, and then cultured with SEM, GW4064, GW3965, Rapamycin (RA) or 3-methyladenine (3-MA), respectively. Mice with hepatic fibrosis also were administrated with SEM, RA or 3-MA to estimate the effect of SEM on autophagy. RESULTS: In vitro, SEM significantly inhibited extracellular matrix deposition, P2 × 7r-NLRP3, and inflammatory cytokines. SEM increased FXR and LXRα/ß expressions and decreased MAPLC3α/ß and P62 expressions, functioning as 3-MA (autophagy inhibitor). In vivo, SEM reduced serum transaminase, histopathology changes, fibrogenesis, autophagy markers and inflammatory cytokines caused by TAA. LX-2 were activated with conditioned medium from LPS-primed THP-1, which resulted in significant enhance of autophagy markers and inflammatory cytokines and decrease of FXR and LXRα/ß expressions. SEM could reverse above these changes and function as 3-MA, GW4064, or GW3965. Deficiency of FXR or LXR attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62 and IL-1ß in activated LX-2. In activated THP-1, deficiency of FXR could decrease the expression of LXR, and vice versa. Deficiency of FXR or LXR in activated MΦ decreased the expressions of FXR and LXR in activated LX-2. Deficiency FXR or LXR in activated MΦ also attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62, caspase-1 and IL-1ß. In vivo, SEM significantly reversed hepatic fibrosis via FXR/LXR and autophagy. CONCLUSION: SEM could regulate hepatic fibrosis by inhibiting fibrogenesis, autophagy and inflammation. FXR/LXR axis-mediated inhibition of autophagy contributed to the regulation of SEM against hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. SEM might be a prospective therapeutic candidate, and its mechanism would be a new direction or strategy for hepatic fibrosis treatment.

Application of Micro-Percutaneous Nephrolithotomy (Micro-PCNL) combined with FURL in 1-2 cm symptomatic, refractory lower calyceal stones.

Objective: To investigate the safety and efficacy of Micro-Percutaneous Nephrolithotomy (Micro-PCNL) combined with flexible ureteroscopic lithotomy (FURL) in the treatment of 1-2 cm symptomatic, refractory lower calyceal stones. Methods: A retrospective analysis was performed concerning the clinical data of 28 patients with 1-2 cm symptomatic, refractory lower calyceal stones. When there was a difficulty in performing FURL in Affiliated Hospital of Hebei University from January 2019 to February 2022, ultrasound-guided F4.8 visual puncture was performed on the lower calyceal stone,with a holmium laser was then used to treat the remaining stones, followed by drainage using a flexible ureteroscopic sheath and postoperative indwelling of the ureteral stent without a nephrostomy tube. The surgery time, intraoperative bleeding and stone-free rate(SFR) were recorded, and the VAS score was used to evaluate the patients' pain status. Results: The surgery was completed successfully in an average of 43.46 ± 10.04 minutes, and the puncture time was 3.46 ± 0.69 minutes. The SFR was 85.71%(24/28) and 92.86%(26/28) at one day and 30 days after surgery, respectively. Two patients with residual stones greater than 0.6 cm in size underwent extracorporeal shock wave lithotripsy four weeks after surgery. Patients were followed up for three months after surgery, and the SFR was revised to 96.43%(27/28). In addition, the VAS scores of all patients decreased significantly from before to after surgery, and the difference was statistically significant(p< 0.05). Conclusion: Micro-Percutaneous Nephrolithotomy (Micro-PCNL) combined with FURL is safe and effective in the treatment of 1-2 cm symptomatic, refractory lower calyceal stones.

Pterostilbene exerts cytotoxicity on activated hepatic stellate cells by inhibiting excessive proliferation through the crosstalk of Sirt1 and STAT3 pathways.

Pterostilbene (PTE), a natural analogue of resveratrol, abundantly exists in blueberries and grapes and has several beneficial potentials against oxidative stress, inflammation, and cancer. In current study, we investigated the effects of PTE on hepatic fibrosis in vitro and in vivo. Activation of hepatic stellate cells (HSCs) is an initiating event in the initiation of hepatic fibrosis. MTT assay revealed that PTE (3.125-12.5 µM) displayed cytotoxicity on activated HSCs, no cytotoxicity on AML-12 and quiescent HSCs. PTE significantly inhibited the expressions of α-SMA, collagen Ⅰ and TIMP-1/MMP13 ratio; suppressed inflammatory cascade activation to reduce inflammatory cytokines release, such as Caspase-1, IL-1ß and IL-6. PTE activated Sirt1 and decreased STAT3 phosphorylation, functioning as SRT1720 and Niclosamide. Sirt1 deficiency significantly elevated p-STAT3 expression, while STAT3 deficiency resulted in Sirt1 increasing and inhibited fibrosis and inflammatory cytokines expressions. In mice with hepatic fibrosis induced by thioacetamide (TAA), PTE significantly decreased ALT and AST activities, reduced fibrosis markers, STAT3 phosphorylation and activated Sirt1 expression. PTE showed cytotoxicity on activated HSCs to ameliorate hepatic fibrosis via regulating fibrogenesis, energy metabolism and inflammation and targeting the crosstalk of Sirt1 and STAT3. In conclusion, PTE could be potentially beneficial as a natural plant metabolite in preventing and treating hepatic fibrosis.

Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial.

BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.

Preparation of water-dispersed monolayer LDH nanosheets by SMA intercalation to hinder the restacking upon redispersion in water.

We present a novel method for preparing water-dispersed monolayer layered double hydroxide (LDH) nanosheets (m-LDH). By intercalating styrene-maleic anhydride copolymer (SMA) into LDH, we obtained m-LDH through a simple aging step that produced stable, translucent colloidal solutions. After drying, the resulting powder can be redispersed in water to recover the m-LDH monolayer structure. To our knowledge, this is the first report of immediate recovery of the m-LDH monolayer structure from dried powder after redispersion in water. Our method may have significant implications for preparing and utilizing m-LDH nanosheets in various applications.

The therapeutic and prognostic role of cuproptosis-related genes in triple negative breast cancer.

BACKGROUND: This study aimed to observe the potential impact of known cuproptosis-related genes (CRGs) on triple negative breast cancer (TNBC) development, as well as their associated molecular mechanisms, immune infiltration mechanisms and potential therapeutic agents. RESULTS: Based on the Cox Proportional Hazard Model, 11 CRGs may be especially important in TNBC development and progression (considered as the Key-TNBC-CRGs). The expression of several Key-TNBC-CRGs (e.g., ATP7A, PIK3CA, LIAS, and LIPT) are associated with common mutations. The SCNA variation of 11 Key-TNBC-CRGs are related to differences immune infiltration profiles. In particular, depletion of ATP7A, ATP7B, CLS, LIAS, and SCL31A1 and while high amplification of NLRP3 and LIPT2 are correlated with decreased immune infiltration. In our Cox proportional hazards regression model, there is a significant difference in the overall survival between high-risk and low-risk groups. The HR in the high-risk group is 3.891 versus the low-risk group. And this model has a satisfactory performance in Prediction of 5-15-year survival, in particular in the 10-year survival (AUC = 0.836). Finally, we discovered some potential drugs for TNBC treatment based on the strategy of targeting 11 Key-TNBC-CRGs, such as Dasatinib combined with ABT-737, Erastin or Methotrexate, and Docetaxel/Ispinesib combination. CONCLUSION: In conclusion, CRGs may play important roles in TNBC development, and they can impact tumor immune microenvironment and patient survival. The Key-TNBC-CRGs interact mutually and can be influenced by common BC-related mutations. Additionally, we established a 11-gene risk model with a robust performance in prediction of 5-15-year survival. As well, some new drugs are proposed potentially effective in TNBC based on the CRG strategy.

A modified triangular Double-J stent for retrograde intrarenal surgery improvement of free-stone rate, and quality of life: a randomized controlled, multiple centers, perspective trial.

PURPOSE: The goal of this study is to evaluate the efficacy and safety of modified triangular double-J (DJ) stent in 1-2 cm renal or ureter calculi after retrograde intrarenal surgery (RIRS) via a randomized, controlled clinical study. METHODS: A total of 196 patients with 1-2 cm renal or ureter calculi who were performed RIRS and received 7Fr modified triangular DJ stents (100 cases) or 6Fr normal DJ stents (96 cases). All operations were performed by experienced surgeons. The clinical characteristics and outcomes were analyzed. RESULTS: There were no significant differences between two groups in terms of age, gender, BMI, location, hydronephrosis, urea WBC, urea RBC, BUN, Cr, laser emission time, operation time, Hb loss, postoperative BUN, postoperative Cr. Patients who received modified triangular DJ stents were shown to have higher stone-free rate (p = 0.038), but lower general health (p = 0.004). CONCLUSION: The modified triangular 7Fr DJ stents were more efficient for patients underwent RIRS than 6Fr normal DJ stents.

Demulsifier-Inspired Superhydrophilic/Underwater Superoleophobic Membrane Modified with Polyoxypropylene Polyoxyethylene Block Polymer for Enhanced Oil/Water Separation Properties.

Demulsifiers are considered the key materials for oil/water separation. Various works in recent years have shown that demulsifiers with polyoxypropylen epolyoxyethylene branched structures possess better demulsification effects. In this work, inspired by the chemical structure of demulsifiers, a novel superhydrophilic/underwater superoleophobic membrane modified with a polyoxypropylene polyoxyethylene block polymer was fabricated for enhanced separation of O/W emulsion. First, a typical polyoxypropylene polyoxyethylene triblock polymer (Pluronic F127) was grafted onto the poly styrene-maleic anhydride (SMA). Then, the Pluronic F127-grafted SMA (abbreviated as F127@SMA) was blended with polyvinylidene fluoride (PVDF) for the preparation of the F127@SMA/PVDF ultrafiltration membrane. The obtained F127@SMA/PVDF ultrafiltration membrane displayed superhydrophilic/underwater superoleophobic properties, with a water contact angle of 0° and an underwater oil contact angle (UOCA) higher than 150° for various oils. Moreover, it had excellent separation efficiency for SDS-stabilized emulsions, even when the oil being emulsified was crude oil. The oil removal efficiency was greater than 99.1%, and the flux was up to 272.4 L·m-2·h-1. Most importantly, the proposed F127@SMA/PVDF membrane also exhibited outstanding reusability and long-term stability. Its UOCA remained higher than 150° in harsh acidic, alkaline, and high-salt circumstances. Overall, the present work proposed an environmentally friendly and convenient approach for the development of practical oil/water separation membranes.

Effect of Hypertension on EPR effect Induced by Polymer Nanomicelles in Renal Cell Carcinoma in vitro.

Objective: To investigate the effect of hypertension on the (enhanced permeability and retention, EPR) effect induced by polymer nanomicelles in renal cell carcinoma in vitro. Methods: A total of 80 patients with renal cell carcinoma treated at the Department of Urology Surgery in the Dept. of Urology of the Affiliated Hospital of Hebei University from Oct. 2019 to Oct. 2020, were analyzed retrospectively. The hypertension group (experimental group) included 40 patients, and the normal blood pressure group (control group) included 40 patients. The diagnosis of renal clear cell carcinoma was confirmed by preoperative auxiliary examinations, such as ultrasonography and CT combined with postoperative pathological analysis. All patients underwent laparoscopic radical nephrectomy for renal cell carcinoma. Polymer nanomicelles (loaded with prolonium iodide) were perfused into the resected kidney specimens within the specified time. The iodine enrichment of polymer nanomicelles in renal tumors was assessed by CT scanning. The peak EPR effect and the time to the peak were statistically compared between the two groups. Results: No significant differences were found in age, sex, location of kidney disease, tumor location or tumor size between the two groups (p> 0.05). The peak (χ̄±S) of the EPR effect in experimental group was 3.60±0.95 ug/cm3 and 3.01±0.96 ug/cm3 in control group, respectively. There was significant difference between the two groups (p< 0.05). The time to the peak of the EPR effect was 3.76±0.75 h in experimental group and 3.82±0.93 hour in control group, respectively. No statistically significant difference was found in the time to the peak of the EPR effect between the two groups (p> 0.05). Conclusion: Hypertension has a certain effect on the EPR effect induced by polymer nanomicelles in renal cell carcinoma in vitro.

The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM: The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS: Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS: Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.