Efficacy and safety of pelvic floor magnetic stimulation combined with mirabegron in female patients with refractory overactive bladder: a prospective study.

Objective: To observe the efficacy and safety of pelvic floor magnetic stimulation (PFMS) combined with mirabegron in female patients with refractory overactive bladder (OAB) symptoms. Patients and methods: A total of 160 female patients with refractory OAB symptoms were prospectively randomized into two groups. Eighty cases in the combination group accepted PFMS and mirabegron therapy and 80 cases as control only accepted mirabegron therapy (The clinical trial registry number: ChiCTR2200070171). The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQol), symptom bother score and OABSS between two groups were compared at the 1st, 2nd and 4th week ends. Results: All of 160 patients were randomly assigned to two groups, of which 80 patients were included in the combination group and 80 in the mirabegron group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week and the 4th week after combination treatment were significantly lower than those in the mirabegron group (p < 0.05). The incidence of drug-related adverse events between two groups was similar, and there was no statistically significant difference (p > 0.05). With respect to secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the mirabegron group between the 2nd week and the 4th week (p < 0.05). This was consistent with the primary outcome. Meanwhile, from the second to fourth week, the OAB-q symptom bother score and OABSS in the combination group were both lower than in the mirabegron group (p < 0.05). Conclusion: Combination therapy of PFMS and mirabegron demonstrated significant improvements over mirabegron monotherapy in reducing refractory OAB symptoms for female patients, and providing a higher quality of life without increasing bothersome adverse effects. Clinical Trial Registration: https://www.chictr.org.cn/, ChiCTR-INR-22013524.

A multilocus-dendritic boronic acid functionalized magnetic nanoparticle for capturing circulating tumor cells in the peripheral blood of mice with metastatic breast cancer.

BACKGROUND: Dynamic fluctuation of circulating tumor cells (CTCs) can serve as an indicator of tumor progression. However, the sensitive isolation of CTCs remains extremely challenging due to their rarity and heterogeneity. Against this dilemma, dendritic boronic acid-modified magnetic nanoparticles (MNPs) were prepared in this study, and polyethyleneimine (PEI) was utilized as a scaffold to significantly increase the number of boronic acid moieties. Then the novel developed material was applied to monitor the number of CTCs in mice with metastatic breast cancer to evaluate the therapeutic effects of matrine (Mat), doxorubicin (Dox), and Mat in combination with Dox. RESULTS: Compared to the low binding capacity of a single boronic acid ligand, dendritic boronic acid shows enhanced sensitivity in binding to sialic acid (SA), which is overexpressed in CTCs. The results showed that the capture efficiency of this modified material could achieve 94.7% and successfully captured CTCs in blood samples from mice with metastatic breast cancer. The CTC counts were consistent with the results of the pathologic examination, demonstrating the reliability and utility of the method. SIGNIFICANCE: The dendritic boronic acid nanomaterials prepared in this study showed high specificity, sensitivity, and accuracy for cancer cell capture. The approach is expected to provide new insights into cancer diagnosis, personalized therapy, and optimization of treatment regimens.

The bioaerosols emitted from toilet and wastewater treatment plant: a literature review.

The aerosols harboring microorganisms and viruses released from the wastewater system into the air have greatly threatened the health and safety of human beings. The wastewater systems, including toilet and wastewater treatment plant (WWTP), are the major locations of epidemic infections due to the extensive sources of aerosols, as well as multifarious germs and microorganisms. Viruses and microorganisms may transport from both toilet and hospital into municipal pipes and subsequently into WWTP, which accounts for the main source of bioaerosols dispersed in the air of the wastewater system. This review aims to elaborate the generation, transmission, and diffusion processes of bioaerosols at toilet and WWTP. Moreover, the main factors affecting bioaerosol transmission and the corresponding prevention strategies for the airborne and inhaled bioaerosols are also discussed. Collectively, this review highlights the importance of managing bioaerosol occurrence in the wastewater system, which has aroused increasing concern from the public.

Effect of salinity on anammox nitrogen removal efficiency and sludge properties at low temperature.

Anaerobic ammonium oxidation (Anammox) process is a new type of biological nitrogen removal technology that is highly efficient, consumes low energy, and is cost-effective. However, from a practical perspective, there are operational problems involved with the technology, due to its special low temperature environmental conditions. As such, the technology is currently a key research direction in the field of sewage control engineering. This study investigated the effect of salinity on the performance of the anammox process at the stress of a low temperature (15℃) and the role salinity has on extracellular polymeric substance (EPS) secretion and by extension, anammox activated sludge. The study tested the technology used to adjust and control salinity at a low temperature. The study found that at a low temperature of 15℃, low salinity can promote the nitrogen removal efficiency of anammox bacteria. Low salinity can also activate anammox bacteria activity. However, in contrast with low salt concentrations, high salt concentrations can inhibit anammox activity. When the temperature was 15℃ and the salinity was 4 g/L, the nitrogen removal efficiency of the reactor was 1.79 times higher than in the environment with unadjusted salinity at 15℃. At a low temperature, as salinity increased, the water binding capacity and flocculation capacity of sludge also increased. Salinity can promote the secretion of EPS and changes its composition. Under low temperature stress, the concentration of salt was less than 12 g/L, and the anammox activity improved. However, a high salinity level significantly inhibited anammox activity.

Characterization of three pathway-specific regulators for high production of monensin in Streptomyces cinnamonensis.

Monensin, a polyether ionophore antibiotic, is produced by Streptomyces cinnamonensis and worldwide used as a coccidiostat and growth-promoting agent in the field of animal feeding. The monensin biosynthetic gene cluster (mon) has been reported. In this study, the potential functions of three putatively pathway-specific regulators (MonH, MonRI, and MonRII) were clarified. The results from gene inactivation, complementation, and overexpression showed that MonH, MonRI, and MonRII positively regulate monensin production. Both MonH and MonRI are essential for monensin biosynthesis, while MonRII is non-essential and could be completely replaced by additional expression of monRI. Transcriptional analysis of the mon cluster by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and electrophoresis mobility shift assays (EMSAs) revealed a co-regulatory cascade process. MonH upregulates the transcription of monRII, and MonRII in turn enhances the transcription of monRI. MonRII is an autorepressor, while MonRI is an autoactivator. MonH activates the transcription of monCII-monE, and upregulates the transcription of monT that is repressed by MonRII. monAX and monD are activated by MonRI, and upregulated by MonRII. Co-regulation of those post-polyketide synthase (post-PKS) genes by MonH, MonRI, and MonRII would contribute to high production of monensin. These results shed new light on the transcriptional regulatory cascades of antibiotic biosynthesis in Streptomyces.

DasR positively controls monensin production at two-level regulation in Streptomyces cinnamonensis.

The polyether ionophore antibiotic monensin is produced by Streptomyces cinnamonensis and is used as a coccidiostat for chickens and growth-promoting agent for cattle. Monensin biosynthetic gene cluster has been cloned and partially characterized. The GntR-family transcription factor DasR regulates antibiotic production and morphological development in Streptomyces coelicolor and Saccharopolyspora erythraea. In this study, we identified and characterized the two-level regulatory cascade of DasR to monensin production in S. cinnamonensis. Forward and reverse genetics by overexpression and antisense RNA silence of dasR revealed that DasR positively controls monensin production under nutrient-rich condition. Electrophoresis mobility shift assay (EMSA) showed that DasR protein specifically binds to the promoter regions of both pathway-specific regulatory gene monRII and biosynthetic genes monAIX, monE and monT. Semi-quantitative RT-PCR further confirmed that DasR upregulates the transcriptional levels of these genes during monensin fermentation. Subsequently, co-overexpressed dasR with pathway-specific regulatory genes monRI, monRII or monH greatly improved monensin production.