ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p.

Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.

Renewable galactomannan-based biogums with structure regulation to protect zinc metal anodes via blocking and confinement effect.

Galactomannan-based biogums were derived from fenugreek, guar, tara, and carob and consisted of mannose and galactose with different ratios, as well as the implementation of high-value utilization was very significant for sustainable development. In this work, renewable and low-cost galactomannan-based biogums were designed and developed as functional coatings protected on the Zn metal anodes. The molecule structure of galactomannan-based biogums were explored on the effect of anticorrosion ability and uniform deposition behavior through the introduction of fenugreek gum, guar gum, tara gum, and carob gum with different ratios of mannose to galactose as 1.2:1, 2:1, 3:1, and 4:1. The existence of biogum protective layers can reduce the contact area between Zn anodes and aqueous electrolyte to enhance the anticorrosion ability of Zn anodes. Rich oxygen-containing groups in galactomannan-based biogums can coordinate with Zn2+ and Zn atoms to form ion conductivity gel layer and adsorb closely on the surface of Zn metal, which can induce uniform deposition of Zn2+ to avoid dendrite growth. Zn electrodes protected by biogums can cycle impressively for 1980 h with 2 mA cm-2 and 2 mAh cm-2. This work can provide a novel strategy to enhance Zn metal anodes' electrochemical performance, as well as implement the high-value application of biomass-based biogums as functional coatings.

Surface Control Behavior toward Crystal Regulation and Anticorrosion Capacity for Zinc Metal Anodes.

The commercial application of high-safety aqueous zinc (Zn) secondary batteries is hindered by the poor cycling life of Zn metal anodes. Here we propose a dendrite growth and hydrogen evolution corrosion reaction mechanism from the binding energy of the deposited crystal plane on the Zn surface and the adsorption energy of H2O molecules on different crystal planes as well as the binding energy of H2O molecules with Zn2+ ions. The biomass-based alkyl polyglucoside (APG) surfactant is adopted as an electrolyte additive of 0.15% to regulate the preferential growth of a parallel Zn(002) plane and enhance the anticorrosion ability of Zn metal anodes. The robust binding and adsorption energies of APG with Zn2+ ions in the aqueous electrolyte and the Zn(002) plane on Zn surface generate a synergistic effect to increase the concentration of Zn2+ ions on the APG-adsorbed Zn(002) plane, endowing the continuous growth of the preferential parallel Zn(002) plane and the excellent anticorrosion capacity. Accordingly, the long-term cycle stability of 4000 h can be achieved for Zn anodes with APG additives, which is better than that with pure ZnSO4 electrolyte. With the addition of APG in the anolyte electrolyte, Zn-I2 full cells display excellent cycling performance (70 mAh g-1 after 20000 cycles) as compared with that without APG additives.

Facile one-step synthesis of PhC2Cu nanowires with enhanced photocatalytic performance.

In recent years, the research of phenylethynylcopper (PhC2Cu) in photocatalysis has attracted immense attention. However, its synthesis requires two steps extending over 9 days. In this paper, the successful preparation of PhC2Cu nanowires is reported using a highly rapid and facile one-step method directly using copper acetate and phenylacetylene as raw materials and ascorbic acid as reducing agent. The kinetic studies indicated that the synthetic reaction follows a pseudo-second-order equation through electrical conductivity. Comparative studies of the crystal structures, morphologies, and optical properties of PhC2Cu prepared by the traditional two-step and the current one-step methods were conducted using XRD, SEM, UV-Vis Drs, FT-IR, Raman spectra, and photocurrent. Meanwhile, the PhC2Cu nanowires exhibited excellent photocatalytic activity to degrade methyl violet (MV) and glyphosate. This facile and rapid method dramatically improves the preparation efficiency of PhC2Cu, and the obtained PhC2Cu also shows higher photocatalytic activity. This remarkable progress enables the possibility of large-scale and efficient preparation of PhC2Cu with high photocatalytic activity, indicating their excellent application prospect in photocatalysis.

Genome-Wide Characterization and Expression Analysis Provide Basis to the Biological Function of Cotton FBA Genes.

Fructose-1,6-biphosphate aldolase (FBA) is a multifunctional enzyme in plants, which participates in the process of Calvin-Benson cycle, glycolysis and gluconeogenesis. Despite the importance of FBA genes in regulating plant growth, development and abiotic stress responses, little is known about their roles in cotton. In the present study, we performed a genome-wide identification and characterization of FBAs in Gossypium hirsutum. Totally seventeen GhFBA genes were identified. According to the analysis of functional domain, phylogenetic relationship, and gene structure, GhFBA genes were classified into two subgroups. Furthermore, nine GhFBAs were predicted to be in chloroplast and eight were located in cytoplasm. Moreover, the promoter prediction showed a variety of abiotic stresses and phytohormone related cis-acting elements exist in the 2k up-stream region of GhFBA. And the evolutionary characteristics of cotton FBA genes were clearly presented by synteny analysis. Moreover, the results of transcriptome and qRT-PCR analysis showed that the expression of GhFBAs were related to the tissue distribution, and further analysis suggested that GhFBAs could respond to various abiotic stress and phytohormonal treatments. Overall, our systematic analysis of GhFBA genes would not only provide a basis for the understanding of the evolution of GhFBAs, but also found a foundation for the further function analysis of GhFBAs to improve cotton yield and environmental adaptability.

CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression.

Circular RNAs (circRNAs) have been implicated in modulating biological processes in some tumors. However, the contributions and molecular mechanisms of circRNAs to gallbladder cancer (GBC) remain largely unknown. In the present study, our results showed circPVT1 expression was significantly upregulated in GBC tissues and cells. Higher circPVT1 expression was correlated with lymph node metastasis, advanced TNM stage, and poor overall survival (OS) in patients with GBC. Subsequently, knockdown of circPVT1 significantly impeded GBC cell proliferation, migration, invasion, while induced cell apoptosis in vitro. However, upregulated circPVT1 had the opposite effects. In vivo, we also demonstrated that knockdown of circPVT1 inhibited tumor growth. Furthermore, we confirmed that circPVT1 could regulate Myeloid cell leukemia-1 (MCL-1) expression by sponging to miR-339-3p, which affected tumor progression in GBC cells. In summary, our findings indicated that circPVT1 may serve as a promising prognostic marker and therapeutic target for GBC.

A highly conductive self-assembled multilayer graphene nanosheet film for electronic tattoos in the applications of human electrophysiology and strain sensing.

Highly conductive, conformable and gel-free electrodes are desirable in human electrophysiology. Besides, intimately coupling with human skin, wearable strain sensors can detect numerous physiological signals, such as wrist pulse and breath. In this study, a multilayer graphene nanosheet film (MGNF) with high conductivity was prepared by the Marangoni self-assembly for using in tattoo dry electrodes (TDEs) and in a graphene tattoo strain sensor (GTSS). Compared to commercial Ag/AgCl gel electrodes, TDEs have lower skin-electrode contact impedance and could detect human electrocardiogram for 24-hour wearing more accurately as well as electromyogram. Through designing a slim serpentine ribbon structure, a resistance-type GTSS, without deterioration even after 2000 cycles, is well demonstrated for human wrist pulse and breath sensing. With the advantages of high conductivity and conformability, MGNF provides support to fabricate low-cost, customizable, and high-performance electronic tattoos for human electrophysiology and strain sensing.

HOTAIR induces the ubiquitination of Runx3 by interacting with Mex3b and enhances the invasion of gastric cancer cells.

BACKGROUND: Long non-coding RNAs (LncRNAs) exert their functions mainly by binding to their corresponding proteins. Runt-related transcription factor 3 (Runx3) is an important transcription factor that functions as a tumor suppressor in gastric cancer. Whether there is an interplay between LncRNAs and Runx3 remains unclear. METHODS: RPISeq was applied to screen the LncRNAs that potentially bind to Runx3. The interaction between LncRNA HOX antisense intergenic RNA (HOTAIR) and Runx3 was validated by RNA Immunoprecipitation and RNA pull-down assays. The role of Mex3b in the ubiquitination of Runx3 induced by HOTAIR was assessed by immunoprecipitation. Pearson's correlation between HOTAIR mRNA expression and Runx3 protein expression was analyzed. Cell migration and invasion were explored by transwell assays. RESULTS: We found that HOTAIR was bound to Runx3 protein and identified the fragment of HOTAIR spanning 1951-2100 bp as the specific binding site. In addition, mex-3 RNA binding family member B (Mex3b) was an E3 ligase involved in HOTAIR-induced ubiquitous degradation of Runx3. Silencing the expression of HOTAIR or Mex3b attenuated the degradation of Runx3. In human gastric cancer tissues, HOTAIR was negatively associated with the expression level of Runx3 protein (Pearson coefficient - 0.501, p = 0.025). Inhibition of HOTAIR significantly suppressed gastric cancer cell migration and invasion through upregulating claudin1, which could be reversed by co-deficiency of Runx3. CONCLUSIONS: These results uncovered the novel interaction between HOTAIR and Runx3, and provided potential therapeutic targets on the metastasis of gastric cancer.

How Could Agronomic Biofortification of Rice Be an Alternative Strategy with Higher Cost-Effectiveness for Human Iron and Zinc Deficiency in China?

BACKGROUND: Iron and zinc deficiencies affect human health globally, especially in developing countries. Agronomic biofortification, as a strategy for alleviating these issues, has been focused on small-scale field studies, and not widely applied while lacking of cost-effectiveness analysis (CEA). OBJECTIVE: We conducted the CEA of agronomic biofortification, expressed as USD per disability-adjusted life years (DALYs) saved, to recommend a cost-effectiveness strategy that can be widely applied. METHODS: The DALYs were applied to quantify the health burden due to Fe and/or Zn deficiency and health cost of agronomic biofortification via a single, dual, or triple foliar spray of Fe, Zn, and/or pesticide in 4 (northeast, central China, southeast, and southwest) major Chinese rice-based regions. RESULTS: The current health burden by Fe or Zn malnutrition was 0.45 to 1.45 or 0.14 to 0.84 million DALYs for these 4 regions. Compared to traditional rice diets, the daily Fe and/or Zn intake from Fe and/or Zn-biofortified rice increased, and the health burden of Fe and/or Zn deficiency decreased by 28% and 48%, respectively. The cost of saving 1 DALYs ranged from US$376 to US$4989, US$194 to US$2730, and US$37.6 to US$530.1 for the single, dual, and triple foliar Fe, Zn, and/or pesticide application, respectively, due to a substantial decrease in labor costs by the latter 2 applications. CONCLUSIONS: Agronomic biofortification of rice with the triple foliar spray of Fe, Zn, and pesticide is a rapidly effective and cost-effectiveness pathway to alleviate Fe and Zn deficiency for rice-based dietary populations.

Metformin Is Associated With Slightly Reduced Risk of Colorectal Cancer and Moderate Survival Benefits in Diabetes Mellitus: A Meta-Analysis.

To systematically assess the effect of metformin on colorectal cancer (CRC) risk and mortality in type 2 diabetes mellitus (T2DM) patients. We conducted a systematic search of PubMed, Web of Science, and the Cochrane Library databases for relevant articles before August 2015. Two investigators identified and extracted data independently. We adopted adjusted estimates to calculate summary estimates with 95% confidence interval (CI) using either a fixed-effects or a random-effects model. Subgroup and sensitivity analyses were conducted to evaluate the robustness of the pooled results. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Begg test and Egger test. Fifteen studies on CRC incidence and 6 studies on CRC survival were finally included in our meta-analysis. The pooled odds ratio (OR) of observational studies illustrated that a slight 10% reduction of CRC incidence was associated with metformin use (OR = 0.90, 95% CI: 0.85-0.96). Furthermore, the pooled hazard ratio (HR) revealed an improved survival outcome for metformin users in CRC patients compared to nonusers (HR = 0.68, 95% CI: 0.58-081). There was no publication bias across studies. Our meta-analysis demonstrated that metformin therapy could slightly reduce CRC incidence and moderately improve the survival outcomes in patients with T2DM. More prospective studies are warranted to certify this protective association.

Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients.

OBJECTIVES: To assess off-treatment virological relapse rates and to determine the role of hepatitis B surface antigen (HBsAg) quantification in predicting virological relapse after stopping entecavir (ETV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). METHODS: One hundred and twelve CHB patients for whom ETV was stopped in accordance with the Asian Pacific Association for the Study of the Liver guidelines stopping rules were enrolled. Patient HBsAg and HBV DNA levels were monitored every 4-12 weeks during ETV treatment and after ETV cessation. Post-treatment virological relapse was defined as a serum HBV DNA level of >10 000 copies/ml after stopping ETV treatment. RESULTS: The virological relapse rate at 52 weeks after stopping ETV was 48.2%. The post-treatment virological relapse rate was significantly higher in patients aged >50 years than in those aged <50 years (p < 0.001), and the virological relapse rate was significantly lower in patients with an HBsAg level <2.0 log10 IU /ml than in those with a level ≥ 2.0 log10 IU /ml at ETV cessation (p = 0.005). An HBsAg level of 2.5 log10 IU/ml at HBeAg seroconversion was the optimal cut-off value for predicting post-treatment virological relapse (p < 0.001). In those aged <50 years and with HBsAg ≤ 2.5 log10 IU/ml at HBeAg seroconversion, the relapse rate was only 5%. In patients with HBsAg ≤ 2.5 log10 IU/ml at HBeAg seroconversion, 52.4% achieved HBsAg levels ≤ 2.0 log10 IU/ml at ETV cessation, while in those with HBsAg >2.5 log10 IU/ml at HBeAg seroconversion, only 4.4% achieved this criterion. CONCLUSIONS: HBsAg levels can help guide the timing of cessation of ETV treatment. HBsAg levels of 2.5 log10 IU/ml at HBeAg seroconversion may be a useful marker to predict virological relapse after the cessation of ETV treatment in HBeAg-positive CHB patients.

Theoretical and experimental studies on the performances of barbital-imprinted systems.

By using density functional theory, we studied the interaction process between barbital and 2-vinyl-4,6-diamino-1,3,5-triazine in acetonitrile at 333 K. Barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were used as the template and functional monomer, respectively. The molecularly imprinted polymer microspheres containing barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were synthesized through precipitation polymerization. After removing the template molecule barbital, the average diameter of the obtained molecularly imprinted polymers was 1.45 µm. By optimizing the molar ratio of barbital and the 2-vinyl-4,6-diamino-1,3,5-triazine, the resulting molecularly imprinted polymers showed the highest adsorption for the barbital. The analysis of the Scatchard plot revealed that the dissociation constant (Kd ) and apparent maximum adsorption quantity (Qmax ) of the molecularly imprinted polymers were 30.69 mg/L and 8.68 mg/g, respectively. The study of selective adsorption showed that molecularly imprinted polymers exhibited higher selectivity for barbtital than that for 1,3-dimethyl barbituric acid and pentobarbital. Herein, the studies can provide theoretical and experimental references for the barbital-imprinted system.

Long-circulating liposomal daptomycin enhances protection against systemic methicillin-resistant Staphylococcus aureus infection with improved therapeutic potential.

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.

[Co-delivery of paclitaxel and cyclosporine by a novel liposome-silica hybrid nano-carrier for anti-tumor therapy via oral route].

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.

[Silica-coated ethosome as a novel oral delivery system for enhanced oral bioavailability of curcumin].

The aim of this study is to investigate the feasibility of silica-coated ethosome as a novel oral delivery system for the poorly water-soluble curcumin (as a model drug). The silica-coated ethosomes loading curcumin (CU-SE) were prepared by alcohol injection method with homogenization, followed by the precipitation of silica by sol-gel process. The physical and chemical features of CU-SEs, and curcumin release were determined in vitro. The pharmacodynamics and bioavailability measurements were sequentially performed. The mean diameter of CU-SE was (478.5 +/- 80.3) nm and the polydispersity index was 0.285 +/- 0.042, while the mean value of apparent drug entrapment efficiency was 80.77%. In vitro assays demonstrated that CU-SEs were significantly stable with improved release properties when compared with curcumin-loaded ethosomes (CU-ETs) without silica-coatings. The bioavailability of CU-SEs and CU-ETs was 11.86- and 5.25-fold higher, respectively, than that of curcumin suspensions (CU-SUs) in in vivo assays. The silica coatings significantly promoted the stability of ethosomes and CU-SEs exhibited 2.26-fold increase in bioavailablity relative to CU-ETs, indicating that the silica-coated ethosomes might be a potential approach for oral delivery of poorly water-soluble drugs especially the active ingredients of traditional Chinese medicine with improved bioavailability.

[The improvement of sample preparation for infrared spectroscopy analysis].

Routine preparation methods of liquid and solid samples for IR analysis are introduced, deficiencies of conventional KBr pellet and liquid film most often used are pointed out and a modified preparation method of sample is put forward, i.e. preparing a liquid film by using two blank KBr pellets or by dipping blank KBr pellet into solution which is the mixture of sample and low boiling point organic solvent. For low boiling point liquid sample, a liquid film is prepared by using two blank KBr pellets; for high boiling point liquid sample, dipping a blank KBr pellet is used; for solid sample, dipping a blank KBr pellet is used as well. From the comparison of routine and modified preparation methods, this new method can meet the need of qualitative analysis and overcome the deficiencies of conventional KBr pellet and liquid film.