Porphyromonas gingivalis with collagen immunization induces ACPA-positive rheumatoid arthritis in C3H mice.

The pathogenic anti-citrullinated protein antibodies (ACPA) are thought to play a vital role in the initiation and immune maintenance of rheumatoid arthritis (RA). However, it is noteworthy that ACPA is not a salient characteristic of any conventional RA animal model. Porphyromonas gingivalis (Pg) is the first microorganism identified to induce citrullination and a target of autoantibodies in early rheumatoid arthritis (RA). Thus, we employed C3H mice with specific MHC types and combined Pg infection with collagen immunity to develop an animal model of ACPA-positive RA. The resulting model exhibited citrullination characteristics, as well as pathological and immune cell changes. 1) Mice showed a significant increase in ACPA levels, and various organs and tissues exhibited elevated levels of citrullinated protein. 2) The mice experienced heightened pain, inflammation, and bone destruction. 3) The spleen and lymph nodes of the mice showed a significant increase in the proportion of Tfh-GCB cell subpopulations responsible for regulating autoantibody production. In conclusion, the C3H mouse model of Pg infection with collagen immunity demonstrated significant alterations in ACPA levels, citrullinated protein expression, and immune cell subpopulations, which could be a crucial factor leading to increased pain, inflammation, and bone destruction.

Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017-2019.

Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children's health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Random-intercept modeling with B-spline was conducted to characterize NAb response kinetics. The NAb titer of CVA16 infection patients was estimated to increase from negative (2.1, 95% confidence interval [CI]: 1.4-3.3) on the day of onset to a peak of 304.8 (95% CI: 233.4-398.3) on day 21 and then remained >64 until 26 mo after onset. However, the NAb response level of EV-A71-infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71-infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4-3.2) increase. When a 4-fold rise in titer was used as the criterion for serological diagnosis of CVA16 and EV-A71 infection, acute-phase serum needs to be collected at 0-5 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6-27.4) and 24.4 d (95% CI: 15.3-38.3) after onset, respectively. In conclusion, both CVA16 and EV-A71 infection induce a persistent humoral immune response but have different NAb response levels and paired-serum sampling times for serological diagnosis. Clinical severity can affect the anti-EV-A71 NAb response.

Integrated aerobic-anaerobic digestion of highly solids-loaded corn stover and swine manure under dynamic aeration: Temperature rise, physicochemical characteristics, and methane production.

This research aimed to design an integrated aerobic-anaerobic reactor with dynamic aeration that was automatically regulated based on real-time oxygen concentration and investigate the aerobic pretreatment and subsequent dry co-anaerobic digestion (co-AD) characteristics of highly solids-loaded corn stover and swine manure in terms of temperature rise, physiochemical characteristics, and methane production. The high-temperature feedstocks from the aerobic pretreatment phase rapidly entered the AD phase without transportation and effectively improved the start-up and methane production of the co-AD. Oxygen concentration range, aeration rate, and pretreatment time affected the cumulative aeration time, temperature rise, and organic matter removal interactively during aerobic pretreatment, and a low aeration rate was relatively preferable. Although the lignocellulose removal increased with the increase in pretreatment duration, the maximal lignin elimination efficiency only reached 1.30%. The inoculum injection in the transition phase from aerobic pretreatment to co-AD and the leachate reflux during co-AD were also critical for producing methane steadily apart from aerobic pretreatment. The cold air weakened the temperature rise of aerobic pretreatment, and the low-temperature leachate reduced the methane production in the co-AD process. An oxygen concentration range of 13%-17%, aeration rate of 0.10 m3/(min·m3), pretreatment time of 84 h, inoculum loading of 40%, leachate refluxing thrice per day, and double-layer inoculation were optimum for improving the integrated aerobic-anaerobic digestion system's ability to resist low temperatures and achieving high methane production. The maximal cumulative and volatile solids (VS) methane yields of corn stover and swine manure reached 444.58 L and 266.30 L/kg VS.

Microplastics' toxic effects and influencing factors on microorganisms in biological wastewater treatment units.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility's central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment.

The association between plain water intake and periodontitis in the population aged over 45: a cross-sectional study based on NHANES 2009-2014.

BACKGROUND: Numerous studies have demonstrated the impact of beverage consumption on overall health and oral health. Specifically, high consumption of sugar-sweetened beverages and coffee has been associated with an increased risk of metabolic disorders and periodontitis. Conversely, high intake of plain water has been linked to various health benefits, including weight management and reduced energy intake. However, no previous studies have explored the potential association between plain water intake and the risk of periodontitis. OBJECTIVES: Our objective was to investigate the relationship between plain water consumption and periodontitis in a middle-aged and elderly population. METHODS: The present cross-sectional study was conducted among participants aged ≥ 45 in the 2009-2014 National Health and Nutrition Examination Surveys. Multivariable regression analysis, subgroup analysis and smooth fitting tests were conducted to explore the independent relationship between plain water intake and periodontitis. RESULTS: A total of 5,882 participants were enrolled,62.02% have periodontitis. Periodontitis patients have lower plain water intake. The multivariable regression tests showed that the risk of periodontitis decreased with increased plain water intake quartiles (Q4 OR = 0.78; 95%CI 0.62-0.96) after fully adjustment. Subgroup analysis and interaction tests showed that gender, age, smoking, diabetes, hypertension or BMI does not significantly interact with the association. However, the relation was significant in males (Q4 OR = 0.64; 95%CI 0.47-0.86) but not in females (Q4 OR = 0.97;95% CI 0.71-1.31). In the smoothed curve fits stratified by gender, the curve for male participants displayed as a U-shape, with an optimal plain water intake at 1200 ml/day. For males drinking plain water less than 1200 ml/day, the risk of periodontitis decreased by 24% with each increase of 500 ml plain water intake (OR = 0.76, 95%CI 0.66-0.87, p < 0.001). CONCLUSIONS: Together, the results showed that plain water intake is negatively associated with periodontitis risk in US middle aged and elderly population. Further studies are needed to investigate the mechanism unites this association. Attention should be given to adequate plain water intake when considering dietary suggestions to the population at high risk of developing periodontitis, especially for men.

In Situ Visualization of Membrane Fouling Evolution during Ultrafiltration Using Label-Free Hyperspectral Light Sheet Fluorescence Imaging.

Profound understanding of fouling behaviors and underlying mechanisms is fundamentally important for fouling control in membrane-based environmental applications. Therefore, it entails novel noninvasive analytical approaches for in situ characterizing the formation and development of membrane fouling processes. This work presents a characterization approach based on hyperspectral light sheet fluorescence microscopy (HSPEC-LSFM), which is capable of discriminating various foulants and providing their 2-dimensional/3-dimensional spatial distributions on/in membranes in a label-free manner. A fast, highly sensitive and noninvasive imaging platform was established by developing a HSPEC-LSFM system and further extending it to incorporate a laboratory-scale pressure-driven membrane filtration system. Hyperspectral data sets with a spectral resolution of ∼1.1 nm and spatial resolution of ∼3 µm as well as the temporal resolution of ∼8 s/plane were obtained, and the fouling formation and development process of foulants onto membrane surfaces, within the pores and on the pore walls were clearly observed during the ultrafiltration of protein and humic substances solutions. Pore blocking/constriction at short times while cake growth/concentration polarization at longer times was found to have coupled effects for the flux decline in these filtration tests, and yet the contribution of each effect as well as the transition of the governing mechanisms was found distinct. These results demonstrate in situ label-free characterization of membrane fouling evolution with the recognition of foulant species during filtration and provide new insights into membrane fouling. This work offers a powerful tool to investigate dynamic processes for a wide range of membrane-based explorations.

Impact of Phenamacril on the Growth and Development of Fusarium pseudograminearum and Control of Crown Rot of Wheat.

Fusarium pseudograminearum is the dominant pathogen causing Fusarium crown rot (FCR) of wheat. Phenamacril is a 2-cyanoacrylate fungicide, having a control effect on diseases caused by Fusarium spp. The objective of this study was to investigate the inhibitory effect of phenamacril on F. pseudograminearum and its control efficacy against FCR. The results showed that phenamacril had a strong inhibitory effect on the mycelial growth of F. pseudograminearum, EC50 values of phenamacril to 63 tested strains were in the range of 0.0998 to 0.5672 µg/ml, and the average EC50 value was 0.3403 ± 0.0872 µg/ml and could be used as the baseline sensitivity of F. pseudograminearum to phenamacril. Phenamacril reduced the germination rate of conidia of F. pseudograminearum, and the EC50 value was 5.0273 to 26.4814 µg/ml. In addition, we found that phenamacril had a teratogenic effect on conidia and blastotubules, which increased the ratio of conidial germination from the middle cells and showed high efficacy on the sporulation quantity of F. pseudograminearum with an EC50 value in the range of 0.0770 to 0.1064 µg/ml. There was no significant correlation between the sensitivity of F. pseudograminearum to phenamacril and its sensitivity to fludioxonil, carbendazim, tebuconazole, and kresoxim-methyl. In vitro and greenhouse assays showed that the treatment with 0.125 µl of active ingredient per gram recorded the best control effect on wheat crown rot, reaching 87.8 and 77.3%, respectively. In two experimental sites in Luoyang, phenamacril also had great control effect against FCR, reaching 83.9%. It was proven that phenamacril has a superior control effect against FCR. This study has laid a foundation for the study of the mechanism of action of phenamacril against F. pseudograminearum and provided a theoretical basis for the application of phenamacril to control FCR.

Solid-phase extraction based on PDMS/ionic liquid sponge followed by gas chromatography-mass spectrometry for rapid and sensitive determination of volatile components in lavender.

INTRODUCTION: Due to the complexity and the low concentrations of volatile components in aromatic plants, sample pretreatment is an important step in the whole analytical procedure. OBJECTIVE: This study aimed to propose a novel, sensitive and fast approach to determine the volatile components in lavender. METHODS: The 1-butyl-3-(propyltrimethoxysilane)imidazolium chloride ([BPtmsim]Cl) ionic liquid was introduced onto the surface of polydimethylsiloxane (PDMS) to prepare a novel PDMS/[BPtmsim]Cl sponge with large surface area, good sorption performance, and reusability. A solid-phase extraction method was developed based on PDMS/[BPtmsim]Cl sponge combined with gas chromatography-mass spectrometry (GC-MS). RESULTS: The effects of the various experimental parameters on the extraction efficiency were investigated. The optimal conditions were [BPtmsim]Cl amount of 0.3 g, 1:4 as the mass ratio of PDMS/[BPtmsim]Cl to lavender sample, microwave power of 700 W, microwave time of 10 min, and n-hexane as the desorption solvent. The method validation results showed good linearity (10-800 µg/ml), high correlation coefficient (R2 ≥ 0.9991), low limits of detection (1.73-2.50 ng/µl), and limits of quantification (4.10-5.11 ng/µl). The interday and intraday precision with relative standard deviation (RSD) values were below 1.93% and 4.71%, respectively. Under the optimal extraction conditions, 16 lavender samples from three different species were analysed and a total of 57 volatile compounds were identified. The correlation between different species of lavender and volatile components was explored using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). CONCLUSION: The results showed that PDMS/[BPtmsim]Cl extraction is a rapid, highly efficient, and sensitive technique for the determination of volatile components in complex plant samples.

The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0-13 years of age: a longitudinal cohort study.

BACKGROUND: A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. METHODS: Two population-based longitudinal cohorts in southern China were studied during 2013-2018. Participants were enrolled in autumn 2013, including 2475 children aged 1-9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. RESULTS: The average maternal antibody transfer ratio was 0.88 (95% CI 0.80-0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9-2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. CONCLUSIONS: Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0-5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.

A case report of an endometriosis cyst at cesarean scar defect and review of literature.

BACKGROUND: Cesarean scar defect (CSD) presents as a cystic defect that connects the uterine cavity at the site of the previous cesarean section (CS). Endometriosis refers to the discovery of endometrial glands and stroma outside the uterine cavity. Cases of endometriosis cysts at CSD have not been reported. CASE PRESENTATION: In this article, we will present a patient with an endometriosis cyst at CSD with symptoms of a prolonged menstrual cycle, periods without cyclic abdominal pain, and a history of cesarean delivery. The gynecologic ultrasound showed a CSD and a mixed mass in the right front of the uterus. After about 1 month, the tumor grew from a diameter of 4.75 cm to 8.06 × 6.23 × 3.66 cm. The patient eventually had an operation, which revealed a mass protruding from the incision in the anterior uterine wall, which was attached to the anterior uterine wall by a thin tip with a smooth surface. Intraoperative rapid cytopathology suggested that endometrial glands were seen within the smooth muscle tissue, similar to endometriosis. Subsequently, the patient underwent resection of the endometriotic cyst. Final paraffin pathology showed smooth muscle with visible endometrial glands and old hemorrhage, and a one-year follow-up showed no recurrence of endometriosis cysts at CSD. CONCLUSIONS: Endometriosis cysts at CSD are very rare. The clinical symptoms may be less obvious, and the diagnosis relies mainly on the patient's previous surgical history and imaging. A finding of a pelvic mass in the location of the CSD, with or without symptoms of menstrual changes and intermittent abdominal pain, should be considered an endometriotic cyst at CSD. Surgical treatment is a good choice for this disease. Further studies are needed regarding the etiological mechanism of this case and why the mass enlarged rapidly in one mouth.

Polydimethylsiloxane/graphene oxide/ß-cyclodextrin sponge as a solid-phase extraction sorbent coupled with gas chromatography-mass spectrometry for rapid adsorption and sensitive determination of lavender essential oil.

An adsorbent polydimethylsiloxane/graphene oxide/ß-cyclodextrin sponge, which possessed the merits of high surface area, chemical stability, environment friendly, and excellent extraction capacity, was successfully fabricated. Based on the advantages, a novel microwave-assisted headspace solid-phase extraction method for lavender essential oil using polydimethylsiloxane/graphene oxide/ß-cyclodextrin sponge as adsorbents was developed in this study. Various experimental parameters were studied. The optimal extraction conditions were as follows: 1 mg/mL as dopamine solution concentration, graphene oxide dosages of 30 mg, microwave power of 700 W, microwave irradiation time of 10 min, and desorption solvent of n-hexane. Under the optimal extraction condition, linearities ranging from 10 to 800 ng were achieved for six representative compounds with a correlation coefficients value of >0.99. The intra-day and inter-day precisions were in the ranges of 0.40-1.56 and 0.67-2.56%, respectively. Finally, the proposed technique was applied to analyze essential oil constituents in 14 samples of three lavender varieties, and 48 compounds were identified. Lavender varieties were distinguished using principal component analysis and partial least squares discriminant analysis. The results showed that the method developed in this study is a novel, simple, and sensitive method for the determination of essential oil in complex plant samples.

De Novo Mutations of CCNK Cause a Syndromic Neurodevelopmental Disorder with Distinctive Facial Dysmorphism.

Neurodevelopment is a transcriptionally orchestrated process. Cyclin K, a regulator of transcription encoded by CCNK, is thought to play a critical role in the RNA polymerase II-mediated activities. However, dysfunction of CCNK has not been linked to genetic disorders. In this study, we identified three unrelated individuals harboring de novo heterozygous copy number loss of CCNK in an overlapping 14q32.3 region and one individual harboring a de novo nonsynonymous variant c.331A>G (p.Lys111Glu) in CCNK. These four individuals, though from different ethnic backgrounds, shared a common phenotype of developmental delay and intellectual disability (DD/ID), language defects, and distinctive facial dysmorphism including high hairline, hypertelorism, thin eyebrows, dysmorphic ears, broad nasal bridge and tip, and narrow jaw. Functional assay in zebrafish larvae showed that Ccnk knockdown resulted in defective brain development, small eyes, and curly spinal cord. These defects were partially rescued by wild-type mRNA coding CCNK but not the mRNA with the identified likely pathogenic variant c.331A>G, supporting a causal role of CCNK variants in neurodevelopmental disorders. Taken together, we reported a syndromic neurodevelopmental disorder with DD/ID and facial characteristics caused by CCNK variations, possibly through a mechanism of haploinsufficiency.

Polydimethylsiloxane/ZIF-8@GO sponge headspace solid-phase extraction followed by GC-MS for the analysis of lavender essential oil.

A novel microwave-assisted (MA) headspace solid-phase extraction (HS-SPE) based on polydimethylsiloxane (PDMS)/ZIF-8@GO sponge was developed for the simultaneous extraction and determination of essential oil constituents in lavender. The PDMS/ZIF-8@GO sponge with a high surface area and excellent adsorption capacity was successfully applied in the HS-SPE process. Microwave-assisted coupled with PDMS/ZIF-8@GO sponge headspace solid-phase extraction followed by GC-MS was proposed. Different experimental parameters were investigated. The optimal conditions were found to be as follows: 2:1 as the quality ratio of ZIF-8 to GO, ZIF-8@GO dosage of 30 mg, microwave power of 600 W, extraction time of 10 min and desorption solvent of n-hexane. This method was successfully applied to the analysis of 11 samples of lavender in different varieties. A total of 52 compounds were identified by the proposed method. A good linearity was observed from 14 to 800 ng with a correlation coefficient (R2) value of >0.99. Multivariate statistical analysis was used to establish the relationship between the varieties and the volatile components for further discriminant analysis. These results demonstrated that the MA-PDMS/ZIF-8@GO is an efficient, sensitive and small sample consumption method for the determination of the essential oil in dried plant materials.

Novel Amphiphilic Dendronized Copolymers Formed by Enzyme-Mediated "Green" Polymerization.

This study reports the first enzyme-mediated polymerization of dendritic macromonomers. The enzyme substrates are prepared by "click" conjugation between tyrosine and hydrophilic triethylene glycol (TrEG)-based dendrons of three generations (G1, G2, and G3). The resulting enzyme-polymerizable dendrons are defect-free as revealed by mass spectrometry, size-exclusion chromatography, and spectroscopic techniques. The phenol-containing macromonomers are water soluble and their polymerizations into dendronized polymers (denpols) are catalyzed by laccase (an oxidoreductase) under benign conditions (45 °C and aqueous medium at pH = 4.0) with copolymer yields between 30 and 40%. The resulting denpols consist of unnatural poly(tyrosine) backbones and dendritic poly(ether-ester) side chains and have molecular masses up to ∼13 000 Da (generation 1), ∼20 000 Da (generation 2), and ∼36 000 Da (generation 3) determined by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analyses. They display amphiphilic properties and self-assemble in aqueous solutions to form aggregates with generation-dependent morphologies.

A Superhydrophobic and Oleophobic Silicone Sponge with Hierarchical Structures.

The fabrication of amphiphobic materials requires a precise and complicated design, especially for 3D porous materials, and amphiphobic sponges have rarely been investigated. This paper describes the synthesis of a superhydrophobic and oleophobic silicone sponge (SS-F) by simply building hierarchical structures, that is, introducing a secondary structure on the pore walls of a hydrophobic and oleophilic silicone sponge. This simple and efficient synthesis method is based on the thiol-ene click reaction. The uniform structure, composition, and hierarchical structures of SS-F are confirmed. The results of the analyses show that the secondary microstructure improves liquid repellency, while the rough and porous surface design ensures durability. Thus, SS-F exhibits good stability, and the amphiphobicity of the surface could withstand scalpel cutting, cyclic compression, extreme temperatures of 250 and -196 °C for 5 h, and long-term storage in an ambient environment. Both its outer and inner surfaces show superhydrophobicity and oleophobicity, which restrict the ability of the adsorption of liquids, enabling its use in oil and water. The introduction of hierarchical structures paves a way for preparing other 3D porous materials.

Mechanically Strong, Autonomous Self-Healing, and Fully Recyclable Silicone Coordination Elastomers with Unique Photoluminescent Properties.

The combination of excellent mechanical performances, high reprocess efficiency, and wide-range tunability for functional dynamic siloxane materials is a challenging subject. Herein, the fabrication of mechanically strong, autonomous self-healing, and fully recyclable silicone elastomers with unique photoluminescent properties by coordination of poly(dimethylsiloxane) (PDMS) containing coordination bonding motifs with Zn2+ ions is reported. Salicylaldimine groups, which are introduced into the polysiloxane backbone via mild Schiff-base reaction, coordinate with zinc ions to form elastomeric networks The obtained supramolecular elastomers have excellent mechanical properties, with the optimized tensile strength up to 10.0 MPa, which is unprecedented among the reported thermoplastic polysiloxane-based elastomers. Both mechanical properties and stress relaxation kinetics are tunable via adjusting the length of PDMS segments or the molar ratio of metal versus salicylaldimine. Furthermore, these elastomers can be conveniently healed and recycled to regain their original mechanical properties and integrity under mild conditions. In addition, this new kind of polysiloxane also exhibits coordination-enhanced fluorescence, showing great promise for preparing photoluminescent elastomers or coatings.

An Amphiphilic PEGylated Peptide Dendron-Gemcitabine Prodrug-Based Nanoagent for Cancer Therapy.

An amphiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron-Gly-Phe-Leu-Gly-GEM (PEGylated dendron-GFLG-GEM), is developed as a nano-prodrug for breast cancer therapy. The self-assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the amphiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self-assembled amphiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.

Impact of mandibular advancement device therapy on cerebrovascular reactivity in patients with carotid atherosclerosis combined with OSAHS.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may affect cerebrovascular reactivity (CVR), representing cerebrovascular endothelial function, through complex cerebral functional changes. This study aimed to evaluate the change of CVR after 1-month and 6-month mandibular advancement device (MAD) treatment of patients with carotid atherosclerosis (CAS) combined with OSAHS. METHODS: Patients with carotid atherosclerosis combined with OSAHS who voluntarily accepted Silensor-IL MAD therapy were prospectively enrolled. All patients underwent polysomnographic (PSG) examinations and CVR evaluation by breath-holding test using transcranial Doppler ultrasound at baseline (T0), 1 month (T1), and 6 months (T2) of MAD treatment. RESULTS: Of 46 patients (mean age 54.4 ± 12.4 years, mean body mass index [BMI] 27.5 ± 4.5 kg/m2), 41 patients (responsive group) responded to the 1-month and 6-month treatment of MAD, an effective treatment rate of 89%. The remaining 5 patients (non-responsive group) were younger (47.4 ± 13.5 years) and had a higher BMI (35.8 ± 1.8 kg/m2). The responsive group had an improvement of apnea-hypopnea index (AHI) (events/h) from 33.0 ± 25.0 (T0) to 12.4 ± 10.4 (T1) and 8.7 ± 8.8 (T2), P < 0.001; minimum arterial oxygen saturation (minSpO2) (%) increased from 79.8 ± 9.1 (T0) to 81.8 ± 9.4 (T1) and 85.2 ± 5.4 (T2), P < 0.01; longest apnea (LA) (s) decreased from 46.5 ± 23.1 (T0) to 33.3 ± 22.7 (T1) and 29.4 ± 18.5 (T2), P < 0.001; T90 (%) decreased from 10.3 ± 14.9 (T0) to 6.1 ± 11.8 (T1) and 3.3 ± 7.5 (T2), P < 0.05. Sleep architecture of these patients also improved significantly. The responsive group had a significant increase in left, right, and mean breath-holding index (BHI): left BHI(/s) from 0.52 ± 0.42 (T0) to 0.94 ± 0.56 (T1) and 1.04 ± 0.64 (T2), P < 0.01; right BHI(/s) from 0.60 ± 0.38 (T0) to 1.01 ± 0.58 (T1) and 1.11 ± 0.60 (T2), P < 0.01; mean BHI(/s) from 0.56 ± 0.38 (T0) to 0.97 ± 0.55 (T1) and 1.07 ± 0.59 (T2), P < 0.01), suggesting improved CVR. CONCLUSION: Effective MAD therapy is beneficial for restoring cerebrovascular endothelial function in patients with CAS and OSAHS in a short period (1 month and 6 months). TRIAL REGISTRATION: Clinical trial registration number: NCT03665818. September 11, 2018.

Polydimethylsiloxane/ionic liquid sponge used in headspace solid-phase extraction coupled with GC-MS for rapid analysis of essential oil in lavender.

A headspace (HS) solid-phase extraction (SPE) based on polydimethylsiloxane (PDMS)/ionic liquid (IL) sponge was developed for the extraction of lavender essential oil. The PDMS after loading of 1-butyl-3-methylimidazolium tetrachloroferrate ([BMIM]FeCl4 ) with a high surface area and excellent adsorption capacity was successfully applied in the SPE process. Microwave distillation (MD) coupled with HS-PDMS/[BMIM]FeCl4 extraction after GC-MS was proposed. Various experimental parameters were studied. The optimal conditions were as follows: optimal IL, [BMIM]FeCl4 ; volume ratio of IL to ethanol, 1:5; extraction solvent, n-hexane; microwave power, 600 W; and irradiation time, 12 min. The limits of detection and quantification of the analytic compounds were in the ranges 4.00-16.32 and 10.00-40.00 ng, respectively. The intra-day and inter-day precisions were in the ranges 0.37-1.94% and 1.20-2.45%, respectively. Under the optimized conditions, 13 samples of 3 lavender varieties were analyzed, and 40 compounds were identified. Lavender varieties were distinguished using principal component analysis. The results showed that MD-HS-PDMS/IL-GC-MS is a novel, simple, and sensitive method for the determination of essential oil in complex plant samples.

Effect of nanoscale bioactive glass with radial spherical particles on osteogenic differentiation of rat bone marrow mesenchymal stem cells.

To validate the feasibility of two types of bioactive glass that contains spherical and radical spherical nano-sized particles in promoting bone repair, we hypothesize that radical spherical nano-sized particles have higher bone repair effectiveness than spherical one due to the physicochemical properties. We rigorously compared the physicochemical properties and bioactivities of these two types of bioactive glass. Specifically, we measured the size, surface morphology, concentration of ionic-dissolution products, bioactivity, and biological effects of two groups of bioactive glass on rat bone marrow mesenchymal stem cells (rBMSCs) and evaluate their effect on proliferation and osteogenic differentiation of rBMSCs in vitro. We observed that spherical nano-bioactive glass (SNBG) was spherical with smooth boundary, while the radial spherical nano-bioactive glass (RSNBG) had radial pore on the surface of particle boundary. When the two materials were immersed in simulated body fluid for 24 h, RSNBG produced more and denser hydroxyapatite carbonate than SNBG. The concentration of Ca and Si ions in RSNBG 24 h extract is higher than that of SNBG, while the concentration of P ions is lower. Proliferation, alkaline phosphatase (ALP) activity, intracellular Ca ion concentrations defined as the number of mineralized nodules produced, and the expression of osteogenic genes were significantly higher in rBMSCs co-cultured with 50 µg/mL RSNBG than SNBG. Overall, these results validated our hypothesis that RSNBG can provide better benefit than SNBG for inducing proliferation and osteogenic differentiation in rBMSCs, in turn suggested the feasibility of this RSNBG in further studies and utilization toward the ends of improved bone repair effectiveness.