Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway.

OBJECTIVE: Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. METHODS: We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. RESULTS: Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. CONCLUSION: Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration. RESULTS: A hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms. CONCLUSION: ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.

A Modularly Designable Vesicle for Sequentially Multiple Loading.

The vesicle is one of the most intriguing platforms for drug delivery, which is believed to improve drug efficacy. In the past few decades, a great deal of materials have been explored to make vesicles, including lipids, block copolymers, dendrons, erythrocyte membranes, and even DNA. Other than shape and size control, most efforts are focused on achieving certain functions, for example, an abundance of stimuli-responsive features are introduced to vesicles, which can be applied to controllable release, such as pH, redox, light, radiation, enzyme etc. Besides, crosslinking or pegylation is used to increase vesicles' stability and elongate circulation time. By incorporating affinity ligands, vesicles can further accumulate to diseased cells or tissues to achieve targeting properties. Recently, multidrug delivery is believed to show a synergy effect in cancer therapy and has become a new direction in this field. However, coloading hydrophilic-hydrophobic small molecules, oligonucleotides, and peptides in the same size- and shape-controlled vesicle through a stepwise manner with high efficiency is still challenging. Herein, a modularly designable vesicle is reported for sequential multiple loading based on frame-guided assembly, which is believed to be an outstanding platform for drug delivery in the future.

An unconventional role of BMP-Smad1 signaling in DNA damage response: a mechanism for tumor suppression.

The genome is under constant attack by self-produced reactive oxygen species and genotoxic reagents in the environment. Cells have evolved a DNA damage response (DDR) system to sense DNA damage, to halt cell cycle progression and repair the lesions, or to induce apoptosis if encountering irreparable damage. The best studied DDR pathways are the PIKK-p53 and PIKK-Chk1/2. Mutations in these genes encoding DDR molecules usually lead to genome instability and tumorigenesis. It is worth noting that there exist unconventional pathways that facilitate the canonical pathways or take over in the absence of the canonical pathways in DDR. This review will summarize on several unconventional pathways that participate in DDR with an emphasis on the BMP-Smad1 pathway, a known regulator of mouse development and bone remodeling.

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer.

Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

A novel single-port robot for total gastrectomy to treat gastric cancer: A case report (with video).

Multiport robots are now widely used for total gastrectomy for gastric cancer, while there is almost a void of research on whether single-port (SP) robots can be used for total gastrectomy. Here, we report a case of a 75-year-old female patient who was diagnosed with gastric cardia adenocarcinoma by gastroscopy and underwent total gastrectomy assisted by the SHURUI SP robot. We successfully accomplished total gastrectomy and D2 lymph node dissection using the novel SP robotic platform. The patient was discharged from the hospital successfully with no complications during or after the surgery. Pathologic diagnosis showed adenocarcinoma of the gastric mucosa with partial signet-ring cell carcinoma, and no metastasis was found in the 29 cleared lymph nodes. The use of the SHURUI SP robot for total gastrectomy in treating gastric cancer is both technically feasible and safe.

Programmed Co-delivery of tamoxifen and docetaxel using lipid-coated mesoporous silica nanoparticles for overcoming CYP3A4-mediated resistance in triple-negative breast cancer treatment.

PURPOSE: This study aims to revolutionize the treatment of aggressive triple-negative breast cancer (TNBC), notorious for its resistance to standard therapies. By ingeniously combining Tamoxifen (TMX) and Docetaxel (DTX) within a lipid-coated mesoporous silica nanoparticle (LP-MSN) delivery system, we intend to enhance therapeutic efficacy while circumventing DTX resistance mediated by CYP3A4 expression. METHODS: We rigorously tested TNBC cell lines to confirm the responsiveness to Docetaxel (DTX) and Tamoxifen (TMX). We adeptly engineered LP-MSN nanoparticles and conducted a thorough examination of the optimal drug release strategy, evaluating the LP-MSN system's ability to mitigate the impact of CYP3A4 on DTX. Additionally, we comprehensively analyzed its pharmacological performance. RESULTS: Our innovative approach utilizing TMX and DTX within LP-MSN showcased remarkable efficacy. Sequential drug release from the lipid layer and mesoporous core curbed CYP3A4-mediated metabolism, substantially enhancing cytotoxic effects on TNBC cells without harming normal cells. CONCLUSION: This pioneering research introduces a breakthrough strategy for tackling TNBC. By capitalizing on synergistic TMX and DTX effects via LP-MSN, we surmount drug resistance mediated by CYP3A4. This advancement holds immense potential for transforming TNBC treatment, warranting further clinical validation.

miR-3195 suppresses the malignant progression of osteosarcoma cells via targeting SOX4.

BACKGROUND: Osteosarcoma (OS) is a highly invasive primary malignancy of the bone that is common in children and adolescents. MicroRNAs (miRNAs) are novel diagnostic and predictive biomarkers for cancers. The miRNA miR-3195 is aberrantly expressed in multiple types of tumors. However, the expression levels and biological functions of miR-3195 in OS remain unclear. METHODS: Two Gene Expression Omnibus (GEO) datasets (GSE69470 and GSE16088) were used to analyze differentially expressed miRNAs and mRNAs in osteosarcoma cell lines and OS tissues. Quantitative RT-PCR was used to detect the expression levels of miR-3195 and the SRY-box transcription factor 4 (SOX4) mRNA in OS tissues and cell lines. The relationship between miR-3195 and the 3'-upstream region (3'-UTR) in the SOX4 mRNA (predicted through bioinformatics) was analyzed using Pearson's correlation analysis and confirmed by a dual-luciferase reporter gene experiment. Cell counting kit-8 assays, colony formation assays, flow cytometry, wound healing assays, transwell assays, and western blotting were performed to explore the effects of miR-3195 levels on SOX4 affected OS cell biological behavior. RESULTS: Our results revealed that miR-3195 was the most down-regulated miRNA and SOX4 was the most up-regulated mRNA by Bioinformatic analysis. It was further confirmed miR-3195 had low expression, and SOX4 had high expression levels in clinical OS tissue samples; the expression levels of both genes were negatively correlated with each other in OS tissues. Overexpression of miR-3195 in OS cell lines significantly inhibited cell proliferation, migration, and invasiveness, while promoting apoptosis; all these effects were reversed by increasing SOX4 expression levels. We also found that miR-3195 could directly bind with the SOX4 gene and down-regulate SOX4 expression. CONCLUSIONS: miR-3195 can modulate proliferation, migration, invasiveness, and apoptosis in OS cells by regulating the SOX4 gene. Thus, the miR-3195/SOX4 signaling may be a novel therapeutic target in OS treatment.

Pharmacokinetics, Safety, and Bioequivalence of 2 Lopinavir/Ritonavir (200/50 mg) Tablets in Healthy Chinese Volunteers: Effect of Food on Absorption.

Lopinavir/ritonavir is an important protease inhibitor for treating HIV-1 infection in patients aged >2 years in combination with other antiretrovirals. The antiviral activity of lopinavir/ritonavir in vivo is mainly derived from lopinavir, while ritonavir improves the bioavailability of lopinavir. This study compared the bioequivalence and safety of 2 lopinavir/ritonavir (200/50 mg) formulations under fasted and fed conditions in healthy Chinese volunteers and compared the pharmacokinetic parameters of lopinavir and ritonavir. A randomized, open-label, single-dose, 4-period, crossover bioequivalence was conducted in 72 subjects under fasted and fed conditions. Lopinavir and ritonavir plasma concentrations were analyzed using validated liquid chromatography with tandem mass spectrometry. Noncompartmental analysis was used to evaluate pharmacokinetic parameters. The 90% confidence intervals of test/reference geometric mean ratio for lopinavir and ritonavir area under the plasma concentration-time curve and maximum drug concentration meets the bioequivalence criteria based on the average bioequivalence method. A high-fat meal delayed the time to the maximum concentration of lopinavir and ritonavir. Therefore, these formulations were bioequivalent in healthy Chinese volunteers under fasting and fed conditions. Moreover, adverse events were more frequent in the fed state, but all were mild.

Construction of a Nomogram Model for Predicting Peritoneal Dissemination in Gastric Cancer Based on Clinicopathologic Features and Preoperative Serum Tumor Markers.

Background: Peritoneal dissemination (PD) is the most common mode of metastasis for advanced gastric cancer (GC) with poor prognosis. It is of great significance to accurately predict preoperative PD and develop optimal treatment strategies for GC patients. Our study assessed the diagnostic potential of serum tumor markers and clinicopathologic features, to improve the accuracy of predicting the presence of PD in GC patients. Methods: In our study, 1264 patients with GC at Fudan University Shanghai Cancer Center and Wenzhou people's hospital from 2018 to 2020 were retrospectively analyzed, including 316 cases of PD and 948 cases without PD. All patients underwent enhanced CT scan or magnetic resonance imaging (MRI) before surgery and treatment. Clinicopathological features, including tumor diameter and tumor stage (depth of tumor invasion, nearby lymph node metastasis and distant metastasis), were obtained by imaging examination. The independent risk factors for PD were screened through univariate and multivariate logistic regression analyses, and the results were expressed with 95% confidence intervals (CIs). A model of PD diagnosis and prediction was established by using Cox proportional hazards regression model of training set. Furthermore, the accuracy of the prediction model was verified by ROC curve and calibration plots. Results: Univariate analysis showed that PD in GC was significantly related to tumor diameter (odds ratio (OR)=12.06, p<0.0006), depth of invasion (OR=14.55, p<0.0001), lymph node metastases (OR=5.89, p<0.0001), carcinoembryonic antigen (CEA) (OR=2.50, p<0.0001), CA125 (OR=11.46, p<0.0001), CA72-4 (OR=4.09, p<0.0001), CA19-9 (OR=2.74, p<0.0001), CA50 (OR=5.20, p<0.0001) and CA242 (OR=3.83, p<0.0001). Multivariate analysis revealed that clinical invasion depth and serum marker of CA125 and CA72-4 were independent risk factors for PD. The prediction model was established based on the risk factors using the R program. The area under the curve (AUC) of the receiver operating characteristics (ROC) was 0.931 (95% CI: 0.900-0.960), with the accuracy, sensitivity and specificity values of 90.5%, 86.2% and 82.2%, respectively. Conclusion: The nomogram model constructed using CA125, CA72-4 and depth of invasion increases the accuracy and sensitivity in predicting the incidence of PD in GC patients and can be used as an important tool for preoperative diagnosis.

Perioperative and short-term outcomes of laparoscopic liver resection for recurrent hepatocellular carcinoma: A retrospective study comparing open hepatectomy.

Background: To compare the perioperative and short-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) in recurrent hepatocellular carcinoma (rHCC) based on propensity score matching (PSM) to investigate therapeutic safety, efficacy, and value for clinical application. Methods: Forty-nine patients with rHCC who underwent surgery at Wenzhou People's Hospital between January 2017 and March 2022 were retrospectively analyzed and classified into LLR (n=30) and OLR (n=22) cases based on the surgical method. Thirty-eight patients were screened using PSM for data analysis to compare basic clinical characteristics, perioperative outcomes, and postoperative recurrence in both groups. Results: Before PSM, the tumour diameter was larger, tumor staging (BCLC staging system), intraoperative blood loss, units of blood transfused, constituent ratio of liver cirrhosis, incidence of MVI and intravascular tumour thrombus and postoperative complication were higher, and duration of hospital stay was significantly longer in the OLR group compared to those in the LLR group (p < 0.05). After PSM, there were no significant differences regarding tumour diameter, MVI incidence, blood transfusion amount or postoperative complication rate in the LLR and OLR groups. The tumor staging, incidence of vascular cancer thrombus, intraoperative blood loss and postoperative duration of hospitalisation were significantly higher in the OLR group than in the LLR group (p<0.05). The difference in recurrence-free survival (RFS) between the two groups was not statistically significant (p = 0.383). Conclusion: LLR for recurrent hepatocellular carcinoma can reduce intraoperative blood loss and postoperative complication rate, shorten the duration of hospitalisation, and is superior to OLR regarding perioperative and short-term efficacy, demonstrating good safety and feasibility.

Cooperative coordination-mediated multi-component self-assembly of "all-in-one" nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer.

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO4 3-) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an "all-in-one" theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Hydroxy-safflower yellow A composites: An effective strategy to enhance anti-myocardial ischemia by improving intestinal permeability.

Hydroxy-safflower yellow A (HSYA) is the chief component of safflower against myocardial ischemia (MI), and belongs to biopharmaceutics classification system (BCS) III drugs. Its structure contains multiple hydroxyl groups, contributing to its high polarity and poor oral bioavailability. The main objective of this study was to probe the potential of oral penetration enhancer n-[8-(2-hydroxybenzoyl) amino] sodium octanoate (SNAC) and cationic copolymer Eudragit®EPO (EPO) to promote absorption of HSYA. HSYA composites (SNAC-HSYA-EPO) were formed by hydrogen bonding and van der Waals force. SNAC-HSYA-EPO has biocompatibility, and can improve the membrane fluidity, uptake, transport, and penetration of Caco-2 cells. The mechanism of promoting of SNAC-HSYA-EPO may be related to energy and P-glycoprotein (P-gp) when compared with the inhibitor NaN3 and verapamil group. In the pharmacokinetic (PK) results, SNAC-HSYA-EPO significantly improved oral bioavailability. Pharmacodynamics (PD) results determined that SNAC-HSYA-EPO could improve the symptoms of MI. The mechanism of the SNAC-HSYA-EPO anti-MI is related to alleviating inflammation and anti-apoptosis to protect the heart. In summary, SNAC-HSYA-EPO prepared in this study possessed a complete appearance, high recombination rate and excellent oral permeability promoting ability. SNAC-HSYA-EPO has the potential to improve oral bioavailability and further enhance the anti-MI effect of HSYA.

Safety and feasibility of laparoscopic surgery for colorectal and gastric cancer under the Chinese multi-site practice policy: admittance standards of competence are needed.

Background: The multi-site practice (MSP) policy has been practiced in China over 10 years. This study aimed to investigate the safety and feasibility of performing laparoscopic surgery for colorectal cancer (LSCRC) and gastric cancer (LSGC) under the Chinese MSP policy. Methods: We collected and analysed the data from 1,081 patients who underwent LSCRC or LSGC performed by one gastrointestinal surgeon in his original hospital (n = 573) and his MSP institutions (n = 508) between January 2017 and December 2020. Baseline demographics, intraoperative outcomes, post-operative recovery, and pathological results were compared between the original hospital and MSP institutions, as well as between MSP institutions with and without specific competence (surgical skill, operative instrument, perioperative multi-discipline team). Results: In our study, 690 patients underwent LSCRC and 391 patients underwent LSGC. The prevalence of post-operative complications was comparable for LSCRC (11.5% vs 11.1%, P = 0.89) or LSGC (15.2% vs 12.6%, P = 0.46) between the original hospital and MSP institutions. However, patients in MSP institutions without qualified surgical assistant(s) and adequate instruments experienced longer operative time and greater intraoperative blood loss. The proportion of patients with inadequate lymph-node yield was significantly higher in MSP institutions than in the original hospital for both LSCRC (11.5% vs 21.2%, P < 0.01) and LSGC (9.8% vs 20.5%, P < 0.01). Conclusion: For an experienced gastrointestinal surgeon, performing LSCRC and LSGC outside his original hospital under the MSP policy is safe and feasible, but relies on the precondition that the MSP institutions are equipped with qualified surgical skills, adequate operative instruments, and complete perioperative management.

Microwave-triggered/HSP-targeted gold nano-system for triple-negative breast cancer photothermal therapy.

Due to the lack of effective therapeutic targets and the passive delivery of a limited quantity of nanoparticles to the tumors, the photothermal conversion agents used in photothermal therapy (PTT) have not been effective in treating triple-negative breast cancer (TNBC). As a result, there is a need to improve the tumor-targeting ability of these photothermal conversion agents. To address this, a microwave-triggered heat shock protein (HSP)-targeted gold nano-system (cmHSP-AuNC), with a gold nanocage (AuNC) as a photothermal conversion agent and anti-HSP monoclonal antibody (cmHSP) as a targeting ligand, was fabricated. cmHSP-AuNC was characterized based on morphology, particle size, zeta potentials, absorption spectrum, and photothermal conversion ability. The expression of HSP70 in 4T1 cells after microwave irradiation was verified by western blotting, and the optimal treatment conditions to achieve the highest expression were determined. Both in vitro and in vivo results indicated that the induction through microwave irradiation could effectively activate the HSP70 overexpression in TNBC, thereby significantly improving the targeting ability, tumor accumulation and anti-tumor efficacy of cmHSP-AuNC. This study proposes a promising strategy for improving the targeting ability and therapeutic efficacy of PTT.

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

BACKGROUND: The complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration. METHODS: The differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman's correlation coefficients and p-values. RESULTS: In two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant. CONCLUSION: These findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.

miR-455-5p suppresses hepatocellular carcinoma cell growth and invasion via IGF-1R/AKT/GLUT1 pathway by targeting IGF-1R.

Hepatocellular carcinoma (HCC) is among the most frequently observed forms of cancer. MicroRNAs (miRNAs) are increasingly thought to play a key role in regulating the onset and progression of a wide range of cancer types. In the present report, we found that miR-455-5p expression was significantly decreased in both HCC patient tumor tissues and cell lines, and that this reduction in expression was linked to poorer patient outcomes. When we overexpressed miR-455-5p in HCC cell lines (Huh7 and HepG2), this was linked with impaired proliferation, colony formation, migration, and invasion. We further found that this miRNA was able to directly bind the insulin growth factor receptor (IGF-1R) 3'-untranslated region, thereby suppressing IGF-1R expression in HCC cells. Consistent with this, miR-455-5p overexpression was associated with reduced glucose transporter (GLUT) 1 expression, which in turn inhibited HCC cell uptake of glucose, production of lactate, and generation of ATP. Together these results thus indicate that mIR-455-5p is able to suppress tumor functionality via impairing glycolysis in HCC cells, highlighting this miRNA as a potential target for anti-cancer therapeutic interventions.

Removal of Antibiotics From Water with an All-Carbon 3D Nanofiltration Membrane.

Recent industrial developments and increased energy demand have resulted in significantly increased levels of environmental pollutants, which have become a serious global problem. Herein, we propose a novel all-carbon nanofiltration (NF) membrane that consists of multi-walled carbon nanotubes (MWCNTs) interposed between graphene oxide (GO) nanosheets to form a three-dimensional (3D) structure. The as-prepared membrane has abundant two-dimensional (2D) nanochannels that can physically sieve antibiotic molecules through electrostatic interaction. As a result, the prepared membrane, with a thickness of 4.26 µm, shows both a high adsorption of 99.23% for tetracycline hydrochloride (TCH) and a high water permeation of 16.12 L m- 2 h- 1 bar- 1. In addition, the cationic dye methylene blue (MB) was also removed to an extent of 83.88%, indicating broad applications of the prepared membrane.

Facile fabrication of ternary TiO2-gold nanoparticle-graphene oxide nanocomposites for recyclable surface enhanced Raman scattering.

A bi-functional ternary nanocomposite was developed by decorating TiO2 and gold nanoparticles on the reduced graphene oxide nanosheets (TiO2-Au-rGO) for recyclable surface enhanced Raman scattering (SERS) detection. TiO2-Au-rGO nanocomposites have been shown to demonstrate the superior SERS performances, which can be used for highly sensitive detection of rhodamine 6 G with a limit of detection of 1.2 × 10-10 M. Subsequently, the surface can be cleaned automatically by the photocatalytic degradation of the adsorbed analytes into inorganic small molecules under visible light irradiation. This can be attributed to the excellent photocatalytic degradation ability, leading to a recyclable SERS application. After being used four times, their excellent SERS and catalytic performances can still be retained. These results suggest that the TiO2-Au-rGO nanocomposites can provide a new strategy for fabricating recyclable SERS substrates, which are highly desirable for SERS practical application.

Effective Removal of Tetracycline Antibiotics from Water using Hybrid Carbon Membranes.

Antibiotic residues in drinking water have become a global problem, especially in developing countries. However, effective purification of water contaminated by antibiotics remains a great challenge. Here, we investigated the removing of tetracycline by carbon nanomaterials with different structures and surface functionalities. The result shows that a membrane of thick graphene oxide (GO) and activated carbon (AC) with a thickness of 15 µm can effectively remove 98.9% of tetracycline hydrochloride (TCH) from water by vacuum filtration. Structural analysis indicated that the AC nanoparticles were uniformly inserted into the GO interstitial sites without any aggregations. Also, GO sheets were loosened by the encapsulated AC nanoparticles, leading to the formation of numerous tiny pores (3-10 nm) that acted as channels for fluid passage, whereas the carbons and chemical groups on the GO surface adsorbed TCH. GO/AC membrane exhibits the best adsorption efficiency among the investigated materials, including pure GO, AC, carbon nanotube (CNT), and CNT/AC and GO/CNT hybrids.