Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis.

bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Genome-wide analysis of BURP genes and identification of a BURP-V gene RcBURP4 in Rosa chinensis.

KEY MESSAGE: Nine RcBURPs have been identified in Rosa chinensis, and overexpression of RcBURP4 increased ABA, NaCl sensitivity, and drought tolerance in transgenic Arabidopsis. BURP proteins are unique to plants and may contribute greatly to growth, development, and stress responses of plants. Despite the vital role of BURP proteins, little is known about these proteins in rose (Rosa spp.). In the present study, nine genes belonging to the BURP family in R. chinensis were identified using multiple bioinformatic approaches against the rose genome database. The nine RcBURPs, with diverse structures, were located on all chromosomes of the rose genome, except for Chr2 and Chr3. Phylogenic analysis revealed that these RcBURPs can be classified into eight subfamilies, including BNM2-like, PG1ß-like, USP-like, RD22-like, BURP-V, BURP-VI, BURP-VII, and BURP-VIII. Conserved motif and exon-intron analyses indicated a conserved pattern within the same subfamily. The presumed cis-regulatory elements (CREs) within the promoter region of each RcBURP were analyzed and the results showed that all RcBURPs contained different types of CREs, including abiotic stress-, light response-, phytohormones response-, and plant growth and development-related CREs. Transcriptomic analysis revealed that a BURP-V member, RcBURP4, was induced in rose leaves and roots under mild and severe drought treatments. We then overexpressed RcBURP4 in Arabidopsis and examined its role under abscisic acid (ABA), NaCl, polyethylene glycol (PEG), and drought treatments. Nine stress-responsive genes expression were changed in RcBURP4-overexpressing leaves and roots. Furthermore, RcBURP4-silenced rose plants exhibited decreased tolerance to dehydration. The results obtained from this study provide the first comprehensive overview of RcBURPs and highlight the importance of RcBURP4 in rose plant.

Long-term exposure to microplastics induces intestinal function dysbiosis in rare minnow (Gobiocypris rarus).

Microplastics are ubiquitous in the natural environment, especially in waters, and their potential impact is also a key issue of concern. In this study, we used 1 µm, 1000 µg/L, polystyrene (PS-MPs) particles to analyze the effects after exposure for 14 and 28 days in rare minnow (Gobiocypris rarus). Results indicated that PS-MPs induce structural alterations in the intestinal tissue, including epithelial damage, villi damage and the inflammatory cell infiltration, while the changes were severer after exposure for 28 days. Polystyrene microplastics also significantly increased the activities of catalase (CAT, increased 142 % and 385 % in 14d and 28d), superoxide dismutase (SOD, increased 17.76 % and 23.43 % in the 14d and 28d) and the content of malondialdehyde (MDA, increased 14.5 % and 442 % in the 14d and 28d), glutathione (GSH, increased 146 % and 298 % in the 14d and 28d). The results not only showed the characterization of gut microbial communities in rare minnow, but also indicated that microbial diversity and composition were altered in gut of fish exposed to PS-MPs. In the control groups, Proteobacteria (31.36-54.54 %), Actinobacteriota (39.99-52.54 %), Fusobacteriota (1.43-1.78 %), Bacteriadota (0.31-0.57 %) were the four dominant bacterial phyla in the intestinal of rare minnow. After exposure to microplastics, In the gut microbiota, the proportion of Proteobacteria increased 9.27 % and 30 % with exposure time, while Actinobacteria decreased 37.89 % and significantly different after 28 days. In addition, metabolomic analysis suggested that exposure to PS-MPs induced alterations of metabolic profiles in rare minnow and differential metabolites were involved in energy metabolism, inflammatory responsible secretion, oxidative stress, nucleotide and its metabolomics. In conclusion, our findings suggest that long-term exposure to microplastics could induce intestinal inflammation, oxidative stress, microbiota dysbiosis and metabolic disorder in rare minnow, and the alterations and severity were exacerbated by prolonged exposure. This study has extended our cognition of the toxicity of polystyrene, and enriched theoretical data for exploring the toxicological mechanism of microplastics.

A High Strength but Fast Fracture-Self-Healing Thermoplastic Elastomer.

Herein, a new type of healable thermoplastic poly(urethane-urea) (PUU) elastomer with a unique dual dynamic network structure consisting of multi-strength hydrogen bonds and aromatic disulfide bonds, is designed and synthesized. The resultant PUU elastomer exhibits high tensile strength (41 MPa), great toughness (104 MJ m-3 ), and excellent self-healing capability (completely severes, heals at 60 ℃ for just 1 h, and recovers more than 80% of the original tensile strength). Although the PUU possesses high-density hydrogen bonds, it is completely homogeneous without micro-phase separation. The unique dual dynamic network structure alleviates the adverse effects of strong molecular interactions on self-healing process, simultaneously endowing the polymer with outstanding mechanical properties and excellent self-healing capability at mild temperature. In addition, the underlying mechanism between performance and structure is revealed. The PUU has potential applications in soft robots and wearable electronics.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Optimization on preparation conditions of Rehmannia glutinosa polysaccharide liposome and its immunological activity.

The aim of this study was to investigate the optimizing preparation conditions and immunological enhancement activity of Rehmannia glutinosa polysaccharide liposome (RGPL). RGPL was prepared using the reverse-phase evaporation method and optimized using the response surface methodology. The immunological enhancement activity of RGPL on splenocyte proliferation was measured. These results showed that the optimum preparation conditions were: a soybean phosphatide to cholesterol ratio of 8:1, a chloroform to methanol ratio of 3:5, a soybean phosphatide to tween 80 ratio of 10:1, a temperature (°C) of 66°C and an entrapment efficiency of 72.753 ± 0.318%. In a single stimulation of drugs, RGPL could significantly promote splenocyte proliferation, specifically at 200 µg mL(-1). Moreover, in a synergistic stimulation of drugs with LPS or PHA, a significant difference was obtained between the RGPL and RGP at 100-400 µg mL(-1), which indicated that the immunological enhancement of RGP was significantly improved after encapsulation with the liposome.

The preparation optimization and immune effect of epimedium polysaccharide-propolis flavone liposome.

The preparation conditions of epimedium polysaccharide-propolis flavone liposome (EPL) were optimized by response surface methodology taking entrapment rates of epimedium polysaccharide and propolis flavone as indexes. The immunoenhancement of EPL prepared with optimized condition was determined taking epimedium polysaccharide-propolis flavone suspension (EPS) and epimedium polysaccharide-propolis flavone watery solution (EPW) as control. The results showed that the optimized preparation condition was as follows: the ratio of drug to lipid was 14:1, the ratio of soybean phospholipid to cholesterol was 6:1, and the ultrasonic time was 19 min. EPL could significantly promote the proliferation of T and B lymphocytes singly or synergistically with PHA or LPS, mRNA expression of IL-2 and IL-6 and secretion of IgG and IgM as compared with EPS and EPW. These results indicated that liposome could significantly improve the immunoenhancement of epimedium polysaccharide-propolis flavone immunopotentiator (EPI) and would be as the suitable dosage form of EPI.

The immunological adjuvant activity of gypenosides liposome against Newcastle disease vaccine.

The adjuvant activity of gypenosides liposome (GPSL) encapsulated with liposome was investigated in vitro and in vivo. In vitro, different concentrations of GPSL were added into chicken's peripheral blood lymphocytes and splenic lymphocyte. The results showed that GPSL could significantly enhance T and B lymphocytes proliferation singly or synergistically with PHA and LPS and the efficacy were superior to those of gypenosides (GPS) and blank liposome (BL) at most of concentrations. In vivo, three hundred and fifty 14-day-old chickens were assigned to 7 groups randomly and vaccinated with Newcastle disease (ND) vaccine. Simultaneously, the chickens in experimental groups were, respectively, oral administration with the GPSL at three doses, GPS and BL. The results showed that GPSL could significantly enhance lymphocyte proliferation, increase antibody titer, and promote cytokine secretion in vitro and in vivo, moreover, the adjuvant activity of GPSL was better than those of GPS and BL. These indicated that formulations of GPS and liposome can further enhance the immune response against ND vaccine compared with the adjuvant alone.

Salidroside liposome formulation enhances the activity of dendritic cells and immune responses.

Salidroside, the important composition, of Rhodiola rosea L. has been reported to have various pharmacological properties. Liposome is known to be effective as drug carriers and immune adjuvant. Therefore, the aim of this study is to investigate immunological adjuvant activity of salidroside liposome. Here we reported the preparation, the effect on DCs in vitro and the immune response in vivo. The immunological adjuvant activity of salidroside liposome formulation was compared with that of salidroside and liposome. The result showed that salidroside liposome formulation not only could promote the maturation of DCs, the stimulation of DCs on MLR proliferation and the antigen presenting ability, but also induced the sustained cellular immune and humoral immune response. Overall, the results showed that salidroside liposome formulation had the potential to act as effective sustained release vaccine delivery systems.

Liposome and epimedium polysaccharide-propolis flavone can synergistically enhance immune effect of vaccine.

Three preparations of epimedium polysaccharide-propolis flavone immunopotentiator (EPI), EPI liposome, EPI suspension and EPI watery solution were prepared. In immune response test, their adjuvanticities were compared in 14-day-old chickens vaccinated with Newcastle disease (ND) vaccine. In immune protection test, the effects of the three preparations on Newcastle disease virus (NDV) infection were compared in chickens vaccinated with ND vaccine then challenged with NDV. The results displayed that EPI liposome could enhance the antibody titer, T lymphocyte proliferation and the concentrations of interferon-γ and interleukin-6, when compared with the other two preparations. In EPI liposome group, the antibody titers, lymphocyte proliferation and protective rate were the highest, while the mortality and morbidity were the lowest, in comparison with the other groups. These results indicated that liposome could enhance the immune effect of EPI on ND vaccine and would be expected as the suitable dosage form of this immunopotentiator.

Optimization on preparation condition of epimedium polysaccharide liposome and evaluation of its adjuvant activity.

The aim of this strategy was to investigate whether the adjuvant activity of epimedium polysaccharide (EPS) could be further enhanced after encapsulated with liposome. In preparation of EPS liposome (EPSL) test, an orthogonal L(9) (3(4)) test design was used to optimize the preparation condition of EPSL. In adjuvant activity test, 350 14-day-old chickens were randomly assigned to 7 groups and vaccinated with Newcastle disease (ND) vaccine. Simultaneously, the chickens in experimental groups were injected with EPSL at three doses, EPS and blank liposome, respectively. The activity of lymphocytes proliferation, titer of serum antibody and concentrations of cytokines were determined. Results showed that the optimal preparation condition of EPSL was that ratio of drug to lipid, ratio of soybean phospholipid to cholesterol, ultrasonic time, and water bath temperature were 1:30, 4:1, 10 min and 40°C, respectively. EPSL could significantly enhance the immune response of ND vaccine and promote cytokines secretion, and its high dose possessed the best efficacy. These findings indicated that liposome encapsulation could significantly improve the adjuvant activity of EPS.

Optimization on condition of glycyrrhetinic acid liposome by RSM and the research of its immunological activity.

The aim of this study is to prepare glycyrrhetinic acid liposome (GAL) and optimize the preparation condition and to investigate further whether liposome could promote the immunological activity of glycyrrhetinic acid (GA). GAL was prepared using a film-dispersion method and the preparation conditions of GAL were optimized with response surface methodology (RSM). Moreover, GAL prepared under the optimal preparation conditions was added into chicken's T and B lymphocytes in vitro. The optimal preparation conditions for GAL by response surface methodology was as follows: ratio 9:1, soybean phospholipid cholesterol (w/w) 2.5:1 and water bath temperature 31 °C. Under these conditions, the experimental encapsulation efficiency of GAL was 83.46 ± 0.55%, which was close with the predicted value. Therefore, the optimized preparation condition is very reliable. The results showed that GAL could significantly promote T and B lymphocytes proliferation singly or synergistically with PHA and LPS and the concentration of immunoglobulins G (IgG) and immunoglobulins M (IgM). These results indicated that liposome could significantly improve the immunological activity of GA and drug action of GA. GAL demonstrates the significant immunological activity, which provides the theoretical basis for the further experiment in vivo.

The immunological activity of propolis flavonoids liposome on the immune response against ND vaccine.

Three hundred and fifty 14-day-old chickens were randomly assigned to 7 groups. At the same time of vaccination with Newcastle disease vaccine, the chickens in experimental groups were injected with propolis flavonoids liposome (PFL) at three doses, PF and blank liposome, respectively. The titer of serum antibody, concentrations of immunoglobulins G (IgG) and immunoglobulins M (IgM), activity of lymphocytes proliferation and concentrations of cytokines were measured. The results showed that three doses of PFL could significantly enhance antibody titer, concentrations of IgG, IgM, and promote lymphocyte proliferation, interferon-γ and interleukin-2 secretion, and its high and medium doses possessed the best efficacy. In general evaluation, the efficacy of PFL was the best, with certain of dose- and time-effect relationships. These findings indicated that the immunological activity of PF could be enhanced with liposome encapsulation.

Immunological adjuvant efficacy of glycyrrhetinic acid liposome against Newcastle disease vaccine.

The aim of this study is to investigate whether the activity of inducing immune response of glycyrrhetinic acid (GA) could be enhanced after GA was encapsulated with liposome. Three hundred and fifty 14-day-old chickens were randomly assigned to 7 groups and vaccinated with Newcastle disease (ND) vaccine. Simultaneously, the chickens in experimental groups were injected with the glycyrrhetinic acid liposome (GAL) at three doses, GA and blank liposome, respectively. The activity of serum antibody titer, concentrations of immunoglobulins G (IgG) and immunoglobulins M (IgM), lymphocytes proliferation, the proportions of lymphocyte subpopulations (CD4(+) and CD8(+)) was determined after vaccination. GAL was evaluated for inducing humoral immunity and cellular immunity in chicken against Newcastle disease (ND) vaccine. The results showed that GAL not only could significantly enhance the antibody titers, IgG and IgM in ND vaccine immunized chicken, but also significantly promote the lymphocyte proliferation and the proportions of CD4(+) and CD8(+), as comparison with GA, BL and VC control groups. Moreover, the effects appear a dose-dependent manner and a time-dependent manner. These indicated that GAL could significantly promote the activation potential of humoral immunity and cellular immunity in chicken and present certain dose-effect and time-effect relationships. The formulations of GA and liposome can further enhance the immune response against ND vaccine compared with the adjuvant alone.

Direct electrochemistry of myoglobin based on ionic liquid-clay composite films.

The direct electron transfer of myoglobin (Mb) was realized by immobilizing Mb onto ionic liquid (1-butyl-3-methyl imidazolium tetrafluoraborate, [bmim][BF(4)])-clay composite film modified glassy carbon electrode. A pair of well-defined redox peaks of Mb with a formal potential (E(o)') of -0.297 V (vs. Ag/AgCl) was observed in 0.1M phosphate buffer solution (pH 6.0). The ionic liquid-clay composite film showed good biocompatibility and an obvious promotion capability for the direct electron transfer between Mb and electrode. The electron transfer rate constant (k(s)) of Mb was calculated to be (3.58+/-0.12)s(-1). UV-vis spectrum suggested that Mb retained its native conformation in the ionic liquid-clay system. Basal plane spacing of clay obtained by X-ray diffraction (XRD) indicated that there was an intercalation-exfoliation-restacking process, in ionic liquid and clay during the drying process of the modification, and the ionic liquid played the key role for promotion of the direct electron transfer between Mb and the ionic liquid-clay composite film modified electrode. The biocatalytic activity of Mb in the composite film was exemplified by the reduction of hydrogen peroxide. Under the optimal conditions, the reduction peak currents of Mb increased linearly with the concentration of H(2)O(2) in the range of 3.90 x 10(-6) to 2.59 x 10(-4)M, with a detection limit of 7.33 x 10(-7)M. The kinetic parameter I(max) and the apparent Michaelis constant (K(m)) for the electrocatalytic reactions were 3.87 x 10(-8)A and 17.6 microM, respectively. The proposed method would be valuable for the construction of a new third-generation H(2)O(2) sensor.