Iron-Confined CRISPR/Cas9-Ribonucleoprotein Delivery System for Redox-Responsive Gene Editing.

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) is a promising gene editing tool to treat diseases at the genetic level. Nonetheless, the challenge of the safe and efficient delivery of CRISPR/Cas9 to host cells constrains its clinical applicability. In the current study, a facile, redox-responsive CRISPR/Cas9-Ribonucleoprotein (RNP) delivery system by combining iron-coordinated aggregation with liposomes (Fe-RNP@L) is reported. The Fe-RNP is formed by the coordination of Fe3+ with amino and carboxyl groups of Cas9, which modifies the lipophilicity and surface charge of RNP and alters cellular uptake from primary endocytosis to endocytosis and cholesterol-dependent membrane fusion. RNP can be rapidly and reversibly released from Fe-RNP in response to glutathione without loss of structural integrity and enzymatic activity. In addition, iron coordination also improves the stability of RNP and substantially mitigates cytotoxicity. This construct enabled highly efficient cytoplasmic/nuclear delivery (≈90%) and gene-editing efficiency (≈70%) even at low concentrations. The high payload content, high editing efficiency, good stability, low immunogenicity, and ease of production and storage, highlight its potential for diverse genome editing and clinical applications.

LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.

Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.

Exploring the underlying mechanisms of enteritis impact on golden pompano (Trachinotus ovatus) through multi-omics analysis.

Enteritis posed a significant health challenge to golden pompano (Trachinotus ovatus) populations. In this research, a comprehensive multi-omics strategy was implemented to elucidate the pathogenesis of enteritis by comparing both healthy and affected golden pompano. Histologically, enteritis was characterized by villi adhesion and increased clustering after inflammation. Analysis of the intestinal microbiota revealed a significant increase (P < 0.05) in the abundance of specific bacterial strains, including Photobacterium and Salinivibrio, in diseased fish compared to the healthy group. Metabolomic analysis identified 5479 altered metabolites, with significant impacts on terpenoid and polyketide metabolism, as well as lipid metabolism (P < 0.05). Additionally, the concentrations of several compounds such as calcitetrol, vitamin D2, arachidonic acid, and linoleic acid were significantly reduced in the intestines of diseased fish post-enteritis (P < 0.05), with the detection of harmful substances such as Efonidipine. In transcriptomic profiling, enteritis induced 68 upregulated and 73 downregulated genes, predominantly affecting steroid hormone receptor activity (P < 0.05). KEGG pathway enrichment analysis highlighted upregulation of SQLE and CYP51 in steroidogenesis, while the HSV-1 associated MHC1 gene exhibited significant downregulation. Integration of multi-omics results suggested a potential pathogenic mechanism: enteritis may have resulted from concurrent infection of harmful bacteria, specifically Photobacterium and Salinivibrio, along with HSV-1. Efonidipine production within the intestinal tract may have blocked certain calcium ion channels, leading to downregulation of MHC1 gene expression and reduced extracellular immune recognition. Upregulation of SQLE and CYP51 genes stimulated steroid hormone synthesis within cells, which, upon binding to G protein-coupled receptors, influenced calcium ion transport, inhibited immune activation reactions, and further reduced intracellular synthesis of anti-inflammatory substances like arachidonic acid. Ultimately, this cascade led to inflammation progression, weakened intestinal peristalsis, and villi adhesion. This study utilized multi-level omics detection to investigate the pathological symptoms of enteritis and proposed a plausible pathogenic mechanism, providing innovative insights into enteritis verification and treatment in offshore cage culture of golden pompano.

Global left ventricular myocardial work: A novel method to assess left ventricular myocardial function and predict major adverse cardiovascular events in maintenance hemodialysis patients.

BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.

Ginsenoside Rb3 inhibits osteoclastogenesis via ERK/NF-κB signaling pathway in vitro and in vivo.

OBJECTIVE: The objective of the study was to determine the anti-osteoclastogenic potential of ginsenoside Rb3 for the treatment of periodontitis. METHODS: The anti-osteoclastogenic effect was determined using RANKL-induced RAW264.7 cells and murine bone marrow-derived macrophages followed by TRAP and phalloidin staining. Expression of osteoclastogenesis-related genes and proteins were examined by qPCR and WB. Activation of signaling pathways was detected by WB and IHC techniques. Experimental periodontitis rat model was built up by gingival injections of P. gingivalis LPS. After 21 days of Rb3 treatment, rats were sacrificed for micro-CT, IHC, H&E, and TRAP staining analyses. RESULTS: Rb3 dramatically inhibits RANKL-induced osteoclastogenesis. Nfatc1, Mmp9, Ctsk, Acp5 mRNA, and MMP9, CTSK proteins were dose-dependently downregulated by Rb3 pretreatment. WB results revealed that Rb3 suppressed activations of p38 MAPK, ERK, and p65 NF-κB, and the inhibition of ERK was most pronounced. Consistently, IHC analysis revealed that p-ERK was highly expressed in alveolar bone surface, blood vessels, odontoblasts, and gingival epithelia, which were notably suppressed by Rb3 treatment. H&E staining and micro-CT analyses showed that Rb3 significantly attenuated gingivitis and alveolar bone resorption in rats. CONCLUSION: Rb3 inhibits RANKL-induced osteoclastogenesis and attenuates P. gingivalis LPS-induced gingivitis and alveolar bone resorption in rats via ERK/NF-κB signaling pathway.

Rapid and Sensitive Detection of Streptococcus iniae in Trachinotus ovatus Based on Multienzyme Isothermal Rapid Amplification.

Infectious diseases caused by Streptococcus iniae lead to massive death of fish, compose a serious threat to the global aquaculture industry, and constitute a risk to humans who deal with raw fish. In order to realize the early diagnosis of S. iniae, and control the outbreak and spread of disease, it is of great significance to establish fast, sensitive, and convenient detection methods for S. iniae. In the present study, two methods of real-time MIRA (multienzyme isothermal rapid amplification, MIRA) and MIRA-LFD (combining MIRA with lateral flow dipsticks (LFD)) for the simA gene of S. iniae were established, which could complete amplification at a constant temperature of 42 °C within 20 min. Real-time MIRA and MIRA-LFD assays showed high sensitivity (97 fg/µL or 7.6 × 102 CFU/mL), which were consistent with the sensitivity of real-time PCR and 10 times higher than that of PCR with strong specificity, repeatability simplicity, and rapidity for S. iniae originating from Trachinotus ovatus. In summary, real-time MIRA and MIRA-LFD provide effective ways for early diagnosis of S. iniae in aquaculture, especially for units in poor conditions.

Molecular characterization and functional analysis of cyp11a and cyp11b in black rockfish (Sebastes schlegelii).

The cyp11 includes cyp11a and cyp11b in most mammals and teleosts, encoded cholesterol side chain lyase and 11ß-hydroxylase, respectively. It is essential in steroid hormone synthesis. However, studies on the regulation of cyp11 are limited, especially in teleosts. In this study, the molecular characterization and function of cyp11a and cyp11b of black rockfish was investigated. Both of them showed high homology with other teleost counterparts by phylogenetic analysis. The expression of cyp11a and cyp11b exhibited a clear sexually dimorphic pattern, with a higher expression level in testis than that of in ovaries. During the different developmental stages (40 dpf, 80 dpf, 190 dpf, 360 dpf, 720 dpf), the expression of cyp11a was earlier than cyp11b. In situ hybridization results showed that cyp11a and cyp11b were mainly expressed in oogonia and oocytes of the ovary. They were located in spermatogonia and interstitial compartment in the 1.5-year-old gonads, and spermatocytesgonia and the peritubular myoid cell of the testis in the 2.5-year-old gonads. To explore the distinct roles of cyp11a and cyp11b in gonads, oestrogen and androgens were used to stimulate the primary testicular and ovarian cells. The expressions of cyp11a and cyp11b were tested under different dose of 17α-methyltestosterone (17α-MT) and 17ß-estradiol (E2). The results showed cyp11a was significantly increased at 10-6  mol ml-1 of 17α-MT and 10-8  mol ml-1 of E2 in ovary and 10-10  mol ml-1 of 17α-MT and E2 in testis, while cyp11b was significantly decreased after 17α-MT and E2 treatment. These results indicated that cyp11a and cyp11b were likely to have different functions, and also implied they might play an important roles in the differentiation of gonads and the synthesis of steroids in black rockfish.

Assessment of left ventricular diastolic function after Transcatheter aortic valve implantation in aortic stenosis patients by echocardiographic according to different guidelines.

BACKGROUND: To evaluate the detailed dynamic change of left ventricular diastolic function (LVDF) by echocardiography in aortic stenosis (AS) patients receiving transcatheter aortic valve implantation (TAVI) and compare LVDF classification according to 2009 ASE/EAE and 2016 ASE/EACVI recommendations. METHODS: Thirty-five AS patients receiving TAVI underwent echocardiography the day before operation (PRE), on the third day (3D), in the first-month (1 M) and the six-month (6 M) after TAVI. LVDF was analyzed using 2D and doppler imaging to get parameters including E/A, E/e', isovolumic relaxation time (IVRT), deceleration time, LA area, LA volume index (LAVI) and systolic tricuspid regurgitation velocity (TR). LVDF classification was evaluated four times for each patient according to 2009 and 2016 recommendations respectively and the results were compared. RESULTS: The decrease of IVRT and TR occurred immediately post surgery up to 1-month. Improvement of E/e' occurred late from 3-day to 1-month. LA area and LAVI decreased continuously shortly after operation till 6-month. Forty-four percent (62/140) by 2009 recommendations were reclassified with different grades when using 2016 guidelines. Comparing PRE and 6 M, with 2009 guidelines, 19 patients improved 1 grade, 8 patients improved 2 grades; with 2016 guidelines, 9 patients improved 1 grade, 13 patients improved 2 grades, 1 patient improved 3 grades. CONCLUSIONS: The conventional 2D echocardiography could effectively reflect variation process of LVDF in AS patients after TAVI. For LVDD classification, obvious differences resulted by the 2009 and updated recommendations were found, and more patients can be regarded as benefiting from TAVI by 2016.

Ginsenoside Rb3 Inhibits Pro-Inflammatory Cytokines via MAPK/AKT/NF-κB Pathways and Attenuates Rat Alveolar Bone Resorption in Response to Porphyromonas gingivalis LPS.

Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 on Porphyromonas gingivalis LPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1ß, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 ameliorated Porphyromonas gingivalis LPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.

The evolution and possible role of two Sox8 genes during sex differentiation in Japanese flounder (Paralichthys olivaceus).

Sox8 genes, as members of the Sox family, have been studied widely in mammals. However, regulation of sox8 genes in teleosts has rarely been studied, and functional analysis of these genes in teleosts has rarely been performed. Here, two duplicates of sox8 genes were identified in Japanese flounder, Posox8a and Posox8b. The analysis of expression showed that Posox8a and Posox8b were expressed in Sertoli cells of the testis, indicating that they play important roles in development and functional maintenance of the testis. Positive selection and phylogenetic analysis found that both Posox8a and Posox8b underwent the purification selection during evolutionary and that sox8 was most likely to be the ancestor sox8a. These results suggested that both Posox8a and Posox8b had important biological functions after generation from three rounds of whole-genome duplication in Japanese flounder. The functional differentiation of Posox8a and Posox8b was verified using cell transfection and dual-luciferase reporter assays; Posox8a overexpression-promoted 3ß-hydroxysteroid dehydrogenase expression and Posox8b overexpression-promoted cytochrome P450 aromatase (cyp19a1; P450arom) expression. Finally, combined with Posox8a and Posox8b expression analysis from 30 to 100 days after hatch, we speculated that Posox8a and Posox8b might participate in the process of sex differentiation and gonadogenesis by regulating sex hormone biosynthesis in the Japanese flounder. Our study is the first to demonstrate the possible mechanism of Posox8a and Posox8b in Japanese flounder sex differentiation and gonadogenesis, laying a solid foundation for functional studies of sox8 genes in teleosts.

Spotted knifejaw (Oplegnathus punctatus) MyD88: Intracellular localization, signal transduction function and immune responses to bacterial infection.

Myeloid differentiation factor 88 (MyD88) links members of the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily to the downstream activation of NF-κB as a "bridge" molecular in response to exogenous pathogen, but the function in spotted knifejaw (Oplegnathus. punctatus), a commercial fish in China, is still unknown. We present a functional analysis of spotted knifejaw MyD88 (OppMyD88) with a typical death domain (DD) at the N-terminus and a conservative Toll/IL-1R (TIR) domain at the C-terminus and suggest that MyD88 is important for the activation of TLR-mediated NF-κB with the synergy between domains. Subcellular localization showed that OppMyD88 was distributed in the cytoplasm in a condensed form. Tissues expression profiling analysis showed that OppMyD88 ubiquitously expressed in all tested tissues with the highest expression in the liver, as determined by real-time PCR. The expression of OppMyD88 significantly upregulated in the liver, spleen, kidney and gills within 120 h post Vibrio anguillarum infection. Moreover, we further confirmed that over-expressed OppMyD88 could also induce apoptosis. These results indicate that OppMyD88 might possess important roles in defense against microbial infection and other biological processes in spotted knifejaw similar to those in mammals, which will deepen our understandings in innate immunity of spotted knifejaw.

Functional Analysis of the Promoter Region of Japanese Flounder (Paralichthys olivaceus) ß-actin Gene: A Useful Tool for Gene Research in Marine Fish.

A newly isolated Japanese flounder (Paralichthys olivaceus) β-actin promoter and its derivative compact construct Poβ-actinΔ−1080/−801Δ−500/−201 have recently been demonstrated to promote ectopic gene expression in cell lines. Different Poβ-actin promoter deletion mutants were constructed and functionally characterized. Mutational analyses by dual-luciferase detected that three regulatory elements, including one enhancer (−1399/−1081) and two silencers (−1080/−801, −500/−201) in the first intron. The sequence located at −1399/−1081 was determined to significantly affect promoter activity. Additionally, the first exon (−1489/−1400) could also remarkably promote the β-actin promoter activity. In the following transduction application, we removed the two silencers and generated a compact reconstruct promoter/enhancer (Poβ-actinΔ−1080/−801Δ−500/−201), which exhibited relatively stronger promoter activity compared with Poβ-actin. Furthermore, the green fluorescent protein (GFP) transgenic stable flounder cell line was obtained by the reconstructed Poβ-actinΔ−1080/−801Δ−500/−201 promoter. Our study provided the potential application of Japanese flounder β-actin, particularly Poβ-actinΔ−1080/−801Δ−500/−201, in ectopic gene expression in the future.

Effects of chromium picolinate supplementation on growth, body composition, and biochemical parameters in Nile tilapia Oreochromis niloticus.

A feeding trial was conducted to evaluate the effects of chromium picolinate (Cr-Pic) on growth performance, body composition, and biochemical parameters in Nile tilapia Oreochromis niloticus. Five experimental diets were formulated with high-protein diet (HP), low-protein diet (LP), and LP + 0.6, 1.2, or 1.8 mg kg-1 Cr, respectively. Each diet was randomly assigned to four replicate groups of 30 fish per aquarium in a water-circulated rearing system for 60 days. Dietary 1.2 or 1.8 mg kg-1 Cr inclusion significantly affects the final body weight, weight gain rate, specific growth rate, feed efficiency rate, and protein efficiency ratio of tilapia compare to the LP diet. The Cr inclusion significantly decreased the content of blood urea nitrogen and the blood glucose level generally with increasing Cr inclusion levels. The Cr content of gill tissue was higher than that of back muscle in all treatments, and the addition of 1.2 or 1.8 mg kg-1 Cr significantly enhanced the Cr contents of back muscle. The cold stress test results showed that adding Cr significantly enhanced the serum T3 concentration and reduced the activity of serum creatine kinase and the serum cortisol level. These results indicated that the supplementation of chromium picolinate can improve the growth performance and reshape the serum protein and carbohydrate metabolism profile and has the potentiality to alleviate the detrimental effects of cold stress in Nile tilapia. The low-protein diet with 1.8 mg kg-1 Cr obtained the same growth performance as the high-protein diet.

Assessment of subclinical left ventricular changes in essential hypertensive patients with hyperuricemia: A three-dimensional speckle-tracking echocardiography study.

OBJECTIVE: To evaluate the effect of hyperuricemia (HU) on subclinical changes of left ventricle (LV) function and structure in patients with hypertension (HT) using three-dimensional speckle-tracking echocardiography (3DSTE) and to explore the relationships between serum uric acid (SUA) levels and three-dimensional speckle tracking echocardiography (3DSTE) parameters in hypertensive and nonhypertensive patients with HU. METHODS: Four age- and sex-matched groups were studied: I: healthy controls, HT- HU- (n = 40); II: HT- HU+ (n = 40); III: HT+ HU- (n = 40); IV: HT+ HU+ (n = 44). Conventional echocardiography and 3DSTE were recorded. Relative wall thickness (RWT) and left ventricular mass index assessed by M-mode echocardiography (LVMi-M) were calculated. 3DSTE parameters including LV volumes and ejection fraction (EF), LVMi-3D, global longitudinal strain (GLS), and global circumferential strain (GCS) were compared. The relationships between SUA levels and 3DSTE parameters were investigated. RESULTS: Despite LV diameters, LV volumes and EF were similar among groups (all p > 0.05), GLS decreased and LVMi-3D increased from controls (group I) to patients with HU or HT alone (group II or III), and patients with both HU and HT (group IV) (all p < 0.05). SUA levels were significantly correlated with the absolute value of GLS (r = -0.461, p < 0.05) and LVMi-3D (r = 0.504, p < 0.05) in hypertensive and nonhypertensive patients with HU. CONCLUSIONS: HU may exacerbate LV systolic dysfunction and remodeling in hypertensive patients, which can be detected by 3DSTE. Early uric acid lowing treatment may be beneficial for hypertensive patients with HU.

Effect of high-fructose corn syrup on Streptococcus mutans virulence gene expression and on tooth demineralization.

High-fructose corn syrup-55 (HFCS-55) has been widely welcomed in recent years as a substitute for sucrose on the basis of its favourable properties and price. The objective of this study was to determine the influence of HFCS-55 on the expression of Streptococcus mutans UA159 virulence genes and on tooth demineralization. Real-time reverse-transcription PCR (real-time RT-PCR) and microhardness evaluations were performed to examine gene expression and enamel demineralization, respectively, after treatment with HFCS-55 and/or sucrose. Significant up-regulation of glucosyltransferase B (gtfB) by HFCS-55 was found. A mixture of HFCS-55 and sucrose could positively enhance expression of glucan-binding protein (gbp) genes. Regarding acidogenicity, expression of the lactate dehydrogenase (ldh) gene was unaffected by HFCS-55. A notable finding in this study was that 5% HFCS-55 significantly enhanced expression of the intracellular response gene of the two-component VicRK signal transduction system (vicR). Demineralization testing showed that the microhardness of teeth decreased by a greater extent in response to HFCS-55 than in response to sucrose. The results indicate that HFCS-55 can enhance S. mutans biofilm formation indirectly in the presence of sucrose and that HFCS-55 has a more acidogenic potential than does sucrose. Summing up the real-time PCR and demineralization results, HFCS-55 appears to be no less cariogenic than sucrose in vitro - at least, not under the conditions of our experiments.

The application of ferrous and graphitic N modified graphene-based composite cathode material in the bio-electro-Fenton system driven by sediment microbial fuel cells to degrade methyl orange.

In this work, the ferrous (Fe2+) and graphitic N modified graphene-based composite cathode materials (N-rGO/Fe3O4) were developed through an in-situ reduction method, aiming to facilitate the two-electron pathway in the oxidation-reduction process. This approach generated a specific concentration of H2O2, enabling the construction of a sediment bio-electro-Fenton system using Fe2+ released from the cathode materials. Notably, this system operates without the need for proton exchange membranes. During the cathode material preparation, the utilization of Fe2+ as a reduction agent for graphene oxide (GO), triggered ammonia water to form graphitic N in graphene sheets. This addition enhanced the two-electron pathway, resulting in increased H2O2 production. Specifically, when the Fe2+ concentration was maintained at 0.1 mol/L, precise preparation of N-rGO/Fe3O4 occurred, leading to a maximum output voltage of 0.528 V and a maximum power density of 178.17 mW/m2. The degradation of methyl orange (MO) reached 68.91% within a 25-h period, a phenomenon contributed to the presence of graphitic N in the graphene sheets. H2O2, a byproduct of the two-electron pathway in cathode oxidation reduction reaction, played a crucial role in constructing the bio-electro-Fenton system. This system, in conjunction with Fe2+ released from N-rGO/Fe3O4, facilitated the complete degradation process of MO.

Potential mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking.

OBJECTIVES: To explore the mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking technology. METHODS: Potential targets of ginseng and periodontitis were obtained through various databases. The intersection targets of ginseng and periodontitis were obtained by using VENNY, the protein-protein interaction network relationship diagram was formed on the STRING platform, the core target diagram was formed by Cytoscape software, and the ginseng-active ingredient-target network diagram was constructed. The selected targets were screened for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The core targets of ginseng's active ingredients in treating periodontitis were analyzed by molecular docking technique. RESULTS: The 22 ginseng's active ingredients, 591 potential targets of ginseng's active ingredients, 2 249 periodontitis gene targets, and 145 ginseng-periodontitis intersection targets were analyzed. Ginseng had strong binding activity on core targets such as vascular endothelial growth factor A and epidermal growth factor receptor, as well as hypoxia induced-factor 1 (HIF-1) signaling pathway and phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. CONCLUSIONS: Ginseng and its active components can regulate several signaling pathways such as HIF-1 and PI3K-Akt, thereby indicating that ginseng may play a role in treating periodontitis through multiple pathways.

Gastrointestinal perforation associated with bevacizumab in metastatic colorectal cancer.

OBJECTIVE: To investigate the risk factors for gastrointestinal perforation in metastatic colorectal cancer patients receiving bevacizumab. METHODS: We retrospectively reviewed 217 patients with metastatic colorectal cancer receiving bevacizumab to investigate the risk factors for gastrointestinal perforation. Three patients occurred intestinal perforation after receiving bevacizumab. We analyzed the clinical characteristics of three patients with intestinal perforation. RESULTS: All patients receiving bevacizumab. Three of 217 patients occurred intestinal perforation after receiving bevacizumab. Patient no. 1 was 70 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. Patient no. 2 was 59 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation after receiving bevacizumab, and recovered smoothly after symptomatic treatment. Patient no. 3 was 60 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. CONCLUSIONS: Patients with advanced colorectal cancer receiving bevacizumab are at risk of gastrointestinal perforation. The patient's age, gender and history of bowel obstruction may be associated with gastrointestinal perforation.

Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Effect of Different Liver Resection Modalities on the Prognosis of Patients with Hepatocellular Carcinoma on the Left Lateral Lobe.

Purpose: To investigate the effect of different liver resection modalities on the prognosis of left lateral lobe hepatocellular carcinoma (HCC) patients. Methods: 315 patients with HCC on left lateral lobe were divided into open left lateral lobectomy (LLL) group (n=249) and open left hepatectomy (LH) group (n=66). The differences in long-term prognosis between two groups were compared. Results: The results showed that narrow resection margin (Hazard Ratio (HR):1.457, 95% Confidential Interval (CI): 1.038-2.047; HR:1.415, 95% CI: 1.061-1.887), tumor diameter > 5 cm (1.645, 1.161-2.330; 1.488, 1.123-1.971), multiple tumors (2.021, 1.330-3.073; 1.987, 1.380-2.861), and microvascular invasion (MVI) (1.753, 1.253-2.452; 1.438, 1.087-1.902) are independent risk factors for overall survival (OS) and tumor recurrence (TR), while liver resection modality is not. After propensity score matching, liver resection modality is not an independent risk factor for OS and TR. Further analysis revealed that wide resection margins were achieved in all patients in the LH group but only 59.0% patients in the LLL group. The OS and TR rates were not significantly different between wide patients with resection margins in LLL group and LH group (P=0.766 and 0.919, respectively), but significantly different between patients with narrow resection margins in LLL group and LH group (P=0.012 and 0.017, respectively). Conclusion: Liver resection modality is not an independent risk factor for the prognosis of patients with HCC on the left lateral lobe as long as wide margins are obtained. Nevertheless, with narrow margins, patients who underwent LH rather than LLL did better.