High-Strength, High-Swelling-Resistant, High-Sensitivity Hydrogel Sensor Prepared with Wood That Retains Lignin.

Wood-derived hydrogels possess satisfactory longitudinal strength but lack excellent swelling resistance and dry shrinkage resistance when achieving high anisotropy. In this study, we displayed the preparation of highly dimensional stable wood/polyacrylamide hydrogels (wood/PAM-Al3+). The alkali-treated wood retains lignin as the skeleton of the hydrogel. Second, Al ions were added to the metal coordination with lignin. Finally, by employing free radical polymerization, we construct a conductive electronic network using polyaniline within the wood/PAM-Al3+ matrix to create the flexible sensor. This approach leverages lignin's integrated structure within the middle lamella to provide enhanced swelling resistance and stronger binding strength in the transverse direction. Furthermore, coordination between lignin and Al ions improves the mechanical strength of the wood hydrogel. Polyaniline provides stable linear pressure and temperature responses. The wood/PAM-Al3+ exhibits a transverse swelling ratio of 3.90% while achieving a longitudinal tensile strength of 20.5 MPa. This high-strength and high-stability sensor is capable of monitoring macroscale human behavior. Therefore, this study presents a simple yet innovative strategy for constructing tough hydrogels while also establishing an alternative pathway for exploring lignin networks in new functional materials development.

Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism.

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

O2-Independent H2O2 Production via Water-Polymer Contact Electrification.

Hydrogen peroxide (H2O2), as a critical green chemical, has received immense attention in energy and environmental fields. The ability to produce H2O2 in earth-abundant water without relying on low solubility oxygen would be a sustainable and potentially economic process, applicable even to anaerobic microenvironments, such as groundwater treatment. However, the direct water to H2O2 process is currently hindered by low selectivity and low production rates. Herein, we report that poly(tetrafluoroethylene) (PTFE), a commonly used inert polymer, can act as an efficient triboelectric catalyst for H2O2 generation. For example, a high H2O2 production rate of 24.8 mmol gcat-1 h-1 at a dosage of 0.01 g/L PTFE was achieved under the condition of pure water, ambient atmosphere, and no sacrificial agents, which exceeds the performance of state-of-the-art aqueous H2O2 powder catalysts. Electron spin resonance and isotope experiments provide strong evidence that water-PTFE tribocatalysis can directly oxidize water to produce H2O2 under both anaerobic and aerobic conditions, albeit with different synthetic pathways. This study demonstrates a potential strategy for green and effective tribocatalytic H2O2 production that may be particularly useful toward environmental applications.

Measuring job stress of dental workers in China during the COVID-19 pandemic: reliability and validity of the hospital consultants' job stress questionnaire.

BACKGROUND: The Hospital Consultants' Job Stress Questionnaire (HCJSQ) has been widely used to assess sources and levels of job stress. However, its reliability and validity among Chinese dental workers have not been extensively studied. The objective of this study was to assess the reliability and validity of the HCJSQ specifically in Chinese dental workers. METHODS: The HCJSQ was used to explore the sources and the global ratings of job stress among Chinese dental workers. To assess the reliability and validity of the HCJSQ, various statistical measures were employed, including Cronbach's alpha coefficient, Spearman-Brown coefficient, Spearman correlation coefficient, exploratory factor analysis, confirmatory factor analysis, convergent validity, and discriminant validity. RESULTS: Of the participants, 526 (17.4%) reported high levels of stress, while 1,246 (41.3%) and 1,248 (41.3%) reported moderate and low levels of stress, respectively. The Cronbach's alpha coefficient for the modified HCJSQ was 0.903, and the Spearman-Brown coefficient was 0.904. Spearman correlation coefficient between individuals' items and the total score ranged from 0.438 to 0.785 (p < 0.05). Exploratory factor analysis revealed that three factors accounted for 60.243% of the total variance. Confirmatory factor analysis demonstrated factor loadings between 0.624 and 0.834 on the specified items. The fit indices of the confirmatory factor analysis indicated good model fit, with a Root Mean Square Error of Approximation of 0.064, Normative Fit Index of 0.937, Comparative Fit Index of 0.952, Incremental Fit Index of 0.952, Tucker-Lewis index of 0.941, and Goodness of Fit Index of 0.944. Additionally, the convergent validity and discriminant validity showed a good fit for the three-factor model. CONCLUSION: The results of this study confirm that Chinese dental workers experience high levels of stress, and the three-factor model of the HCJSQ proves to be a suitable instrument for evaluating the sources and levels of job stress among Chinese dental workers. Therefore, it is imperative that relevant entities such as hospitals, medical associations, and government take appropriate measures to address the existing situation.

Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus.

BACKGROUND: Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet. METHODS: The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays. RESULTS: hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods. CONCLUSIONS: These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.

Integrative mRNA-miRNA interaction analysis associated with the immune response of Strongylocentrotus intermedius to Vibrio harveyi infection.

Strongylocentrotus intermedius is one of the most economically valuable sea urchin species in China and has experienced mass mortality owing to outbreaks of bacterial diseases such as black mouth disease. This has caused serious economic losses to the sea urchin farming industry. To investigate the immune response mechanism of S. intermedius with different tube feet colors in response to Vibrio harveyi infection, we examined the different tube feet-colored S. intermedius under V. harveyi challenge and compared their transcriptome and microRNA (miRNA) profiles using RNA-Seq. We obtained 1813 differentially expressed genes (DEGs), 28 DE miRNAs, and 303 DE miRNA-DEG pairs in different tube feet-colored S. intermedius under V. harveyi challenge. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the most significant DEGs were associated with the Notch signaling and phagosome pathways. The target genes of immune-related miRNAs (miR-71, miR-184, miR-193) and genes (CALM1, SPSB4, DMBT, CSRP1) in S. intermedius were predicted and validated. This study provides insight into the molecular mechanisms that regulate genes involved in the immune response of S. intermedius infected with V. harveyi.

Photoaging of Typical Microplastics as Affected by Air Humidity: Mechanistic Insights into the Important Role of Water Molecules.

Recent studies showed that land is the most important sink for microplastics (MPs); however, limited information is available on the photoaging processes of land surface MPs that are exposed to the air. Herein, this study developed two in situ spectroscopic methods to systematically explore the effect of air humidity on MP photoaging using a microscope of Fourier transform infrared spectroscopy and a laser Raman microscope, which were equipped with a humidity control system. Polyethylene microplastics, polystyrene microplastics, and poly(vinyl chloride) microplastics (PVC-MPs) were used as model MPs. Our results showed that relative humidity (RH) could significantly influence the MP surface oxygen-containing moieties generated from photo-oxidation, especially for PVC-MPs. As the RH level varied from 10 to 90%, a decrease in the photogenerated carbonyl group and an increase in the hydroxyl group were observed. This could be attributed to the involvement of water molecules in the production of hydroxyl groups, which subsequently inhibited carbonyl generation. Moreover, the adsorption of coexisting contaminants (i.e., tetracycline) on photoaged MPs exhibited strong RH dependence, which could be assigned to the varied hydrogen bonding between tetracycline carbonyls and aged MP surface hydroxyls. This study reveals a ubiquitous but previously overlooked MP aging route, which may account for the changed MP surface physiochemical properties under solar irradiation.

Natural Solar Irradiation Produces Fluorescent and Biodegradable Nanoplastics.

Nanoplastics (NPs) have raised global concern owing to their potential health effects. Herein, after simulated and natural solar irradiation, polyethylene, polypropylene, polystyrene, and poly(vinyl chloride) nanoplastics (PVC NPs) were observed to exhibit enhanced fluorescence, particularly PVC NPs. Furthermore, the role of photoaged NPs as a potential fluorescence indicator was evaluated by exposing a model aquatic organism Daphnia magna to these NPs. Our results revealed that photoaged NPs exhibited strong fluorescence owing to the generation of conjugated π bonds, which can achieve π-π* electron transition with low energy consumption. Photogenerated fluorescence also enabled the photoaged NPs to act as efficient fluorescent tracers, which can help track NP migration in various organisms. The results of two-photon laser confocal scanning microscopy revealed that the photoaged NPs could translocate across biological barriers and accumulate in extraintestinal tissues in addition to being ingested and excreted. Moreover, compared with pristine NPs, the photoaged NPs underwent biodegradation more easily, probably because of increased hydrophilicity due to photogenerated oxygen-containing moieties. Therefore, in addition to producing fluorescent NPs without the attachment of external fluorescent dyes, the natural photoaging process can promote the migration and degradation of photoaged NPs in food chains.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

The prevalence of professional burnout among dentists: a systematic review and meta-analysis.

Professional burnout refers to mental weariness caused by occupational stress. However, there is a lack of systematic studies on the prevalence of professional burnout among dentists. The purpose of this study was to investigate the prevalence of professional burnout among dentists. Databases including PubMed, PsycINFO, Embase, Cochrane, and Web of Science were systematically searched from inception to 28 October 2021. The random-effects model and forest plots were used to assess the pooled prevalence of professional burnout among dentists. A total of 15 studies with a total of 6038 study subjects were included in the meta-analysis, and the overall professional burnout among dentists was 13% (95%CI: 6-23). Subgroup analysis suggested a high prevalence of burnout in Europe, and the least in the Americas. The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago. This meta-analysis demonstrated that the prevalence of burnout was relatively low among dentists, and there was a downward trend. Therefore, it is important to continue to pay close attention to the mental health of dentists and effectively prevent and treat professional burnout to better maintain the provision of health care services.

The overall prevalence of professional burnout among dentists was 13%.Subgroup analysis revealed that the prevalence of burnout differed in geographical regions, with the highest in Europe, followed by Asia, and the lowest in America.The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago.More attention should be paid to professional burnout among dentists to improve the provision of health care services.

Study on the Relationship between the Structure and Pyrolysis Characteristics of Lignin Isolated from Eucalyptus, Pine, and Rice Straw through the Use of Deep Eutectic Solvent.

Understanding the pyrolysis product distributions of deep eutectic solvent (DES)-isolated lignins (DESLs) from different types of biomass is of great significance for lignin valorization. The structure and pyrolysis properties of DESLs obtained from eucalyptus (E-DESL), pine (P-DESL), and rice straw (R-DESL) were studied through the use of various methods such as elemental analysis, GPC, HS-GC, and NMR techniques, and the pyrolysis characteristics and product distributions of the DESLs were also further investigated through the use of TGA, Py-GC/MS, and tubular furnace pyrolysis. DESLs with high purity (88.5-92.7%) can be efficiently separated from biomass while cellulose is retained. E-DESL has a relatively low molecular weight, and P-DESL has a relatively higher hydrogen-carbon effective ratio and a lower number of condensation structures. The Py-GC/MS results show that, during DESL pyrolysis, the monomeric aromatic hydrocarbons, p-hydroxyphenyl-type phenols, and catechol-type phenols are gradually released when the guaiacyl-type phenols and syringyl-type phenols decrease with the rising temperature. 4-methylguaiacol and 4-methylcatechol, derived from the guaiacyl-type structural units, are positively correlated with temperature, which causes a significant increase in products with a side-chain carbon number of 1 from P-DESL pyrolysis. 4-vinylphenol, as a representative product of the R-DESL, derived from p-hydroxyphenyl-type structural units, also gradually increased. In addition, the P-DESL produces more bio-oil during pyrolysis, while gases have the highest distribution in E-DESL pyrolysis. It is of great significance to study the characteristic product distribution of lignin isolated through the use of DES for lignin directional conversion into specific high-value aromatic compounds.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

Management of burning mouth Syndrome: A position paper of the Chinese Society of Oral Medicine.

BACKGROUND: Burning mouth syndrome is a syndrome with tongue as the main affected site and burning pain as the main complaint. Although a variety of therapies have been reported to treat BMS, there is a lack of widely recognized therapies and it is still a dilemma for clinicians to treat BMS. OBJECTIVE: To develop the position paper and provide the references for clinical practice of BMS in China. METHODS: Under the guidance of WHO (World Health Organization) Handbook for Guideline Development, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach as a tool to develop this position paper in the following steps: setting up the groups, formulating the clinical questions and choosing the outcomes, retrieving and synthesizing of evidence, assessing the evidence, investigating the patients' values and preferences, developing the recommendations, reviewing the recommendations, and writing the position paper. RESULTS: The 27 recommendations were formed from the following 7 aspects: pre-treatment examination, removal of stimuli, medication, physical therapy, psychological therapy, and antipsychotics. There are 3 strong recommendations and 12 weak recommendations in pre-treatment examination and removal of stimuli, as well as 12 weak recommendations in therapies. CONCLUSION: The Chinese position paper for management of BMS has been developed, which could provide the references for clinical practice of BMS in China. Twenty-seven recommendations were formed based on consensus of experts on the balance of benefits vs side effects, evidence, cost, and patients' values and preferences, although the quality of evidence is relatively low.

Biocompatibility evaluation of heparin-conjugated poly(ε-caprolactone) scaffolds in a rat subcutaneous implantation model.

Vascular grafts prepared from synthetic polymers have serious shortcomings that can be resolved by surface modification, such as by immobilizing heparin. In this study, the mechanical properties, biocompatibility, anticoagulation property, and water contact angle of two heparin-conjugated poly(ε-caprolactone) scaffolds (PCL-hexamethylendiamine-heparin, PCL-HMD-H. PCL-lysine-heparin, PCL-LYS-H) were compared to identify a preferred heparin conjugation method. An evaluation of the subcutaneous tissue biocompatibility of the scaffolds demonstrated that PCL-HMD-H had better endothelial cell proliferation than the PCL-LYS-H and was therefore a promising scaffold candidate for use in vascular tissue-engineering.

Epigenetics-Based Tumor Cells Pyroptosis for Enhancing the Immunological Effect of Chemotherapeutic Nanocarriers.

Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.

Application of a hybrid gravity-driven membrane filtration and dissolved ozone flotation (MDOF) process for wastewater reclamation and membrane fouling mitigation.

This study proposed a novel membrane filtration and dissolved ozone flotation integrated (MDOF) process and tested it at pilot scale. Membrane filtration in the MDOF process was operated in gravity-driven mode, and required no backwashing, flushing, or chemical cleaning. Because ozone was added in the MDOF process, ozonation, coagulation, and membrane filtration could occur in a single reactor. Moreover, in situ ozonation occurred in the MDOF process, which differs from the conventional pre-ozonation membrane filtration process. Significant enhancement of turbidity removal was further achieved through the addition of membrane filtration. Membrane fouling was mitigated in the MDOF process compared to the MDAF process. In situ ozonation in the MDOF process decreased the fluorescence intensity and transformed the high MW dissolved organics into small MW compounds. For the fouling layer, the extracellular polymeric substance (EPS) contents and cake layer morphology were analyzed. The results indicated that the contents of EPS decreased. Furthermore, a thinner and more loosely structured cake layer formed in the MDOF process. Because coagulation and ozonation occurred simultaneously in a single reactor, the generation of hydroxyl radicals was enhanced through the catalytic effect of Al-based coagulants on ozone decomposition, which further alleviated membrane fouling in the MDOF process.

Comparison of Clinical Outcomes of Prostatic Artery Embolization with 50-µm Plus 100-µm Polyvinyl Alcohol (PVA) Particles versus 100-µm PVA Particles Alone: A Prospective Randomized Trial.

PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-µm and 100-µm polyvinyl alcohol (PVA) particles versus 100-µm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-µm plus 100-µm PVA particles (group A) or 100-µm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Qmax to < 7 mL/s. RESULTS: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Qmax (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group. CONCLUSIONS: PAE with 50-µm plus 100-µm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-µm PVA particles alone.

"Bottom-up" Construction of Multi-Polyprodrug-Arm Hyperbranched Amphiphiles for Cancer Therapy.

Despite the great advantages of polymer-drug conjugates (PDC) in cancer therapy, control of the drug loading site and degree via a facile approach remains a great challenge. Herein, by combining the controllability of the "bottom-up" strategy and the stability of multiarm hyperbranched amphiphiles, we have developed novel multi-polyprodrug-arm hyperbranched amphiphiles (H40-star-(PHCPTMA-b-PMPC), hPCM) via reversible addition-fragmentation chain transfer (RAFT) polymerization for cancer therapy. The hPCM was constructed via two-step polymerization of an acid-labile prodrug monomer and a zwitterionic monomer, respectively. By using an H40 macroRAFT agent, 10-hydroxycamptothecine (HCPT) prodrug monomers were directly polymerized via the "bottom-up" strategy as a polyprodrug-arm inner-shell of hPCM with homogeneous drug distribution. The drug loading content can be facilely tuned through variation of the feed ratio of HCPTMA/H40 macroRAFT agent. Finally, the poly-zwitterionic hydrophilic outer-shell of hPCM was formed by RAFT polymerization of zwitterionic monomer to ensure preferable biocompatibility. By dissolving in dilute solution, unimolecular micelles of hPCM can be obtained, which endow desirable stability for the micelles. The effective cellular internalization, extended blood retention time, considerable accumulation in tumor tissue, and excellent anticancer activity of the hPCM micelles have been evaluated both in vitro and in vivo. This novel multi-polyprodrug-arm hyperbranched amphiphile constructed via the "bottom-up" strategy may open up new horizons for exploring next-generation PDC-based drug delivery systems.

Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease.

Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.

Structure-based antigenic epitope and PEGylation improve the efficacy of staphylokinase.

Staphylokinase (Sak) holds promise for use in thrombolytic therapy for acute myocardial infarction. However, its immunogenicity is a major disadvantage under clinical conditions. PEGylation has become a sophisticated method to decrease that immunogenicity. In this report, according predicted epitope from the active center, five residues, including Gly79, Leu82, Lys84, Ala97, and Arg104 have been mutant as cysteine for mono PEGylation, respectively. According to the relative immunogenicity of Sak or its PEGylation derivatives, the amount of specific anti-Sak IgG antibodies elicited by PEGylation proteins, including C79G, C82L, C84K, C97A, and C104R in BALB/c mice decreased by approximately 15-75% each. PEGylated Sak derivatives showed a decrease of up to 75% in the immune reactivity in PEG-Sak-C104R. Thrombelastography experiments showed that two PEG-conjugated derivatives, PEG-Sak-C97A (Ly30, 68.14 ± 2.51%) and PEG-Sak-C104R (Ly30, 66.49 ± 5.97%), the LY30 of PEG-Sak-C97A, and PEG-Sak-C104R produced values very similar to those of wild-type Sak. The fibrin plate assays showed the bioactivity of PEG-Sak-C104R to exhibit the most activity approximately as much as urokinase (diameter of halo pattern, 18.6 ± 1.06 mm) and tPA (diameter of halo pattern, 17.2 ± 0.49 mm). The Sak PEGylation derivative PEG-Sak-C104R was also selected for further in vivo activity experimentation. The thrombolytic ability of PEG-Sak-C104R is a little lower than wild-type Sak, whereas, this PEGylated protein retained high activity suitable for thrombolytic therapy. Collectively, with the in vivo and in vitro experiments, the present study suggests that site mutant PEGylation, PEG-Sak-C104R, is a suitable type of PEGylation for clinical applications. Further optimization would help maintain the bioactivity and decrease the immunogenicity of staphylokinase.