Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

Fluoride removal from coal mining water using novel polymeric aluminum modified activated carbon prepared through mechanochemical process.

Defluoridation of coal mining water is of great significance for sustainable development of coal industry in western China. A novel one-step mechanochemical method was developed to prepare polymeric aluminum modified powder activated carbon (PAC) for effective fluoride removal from coal mining water. Aluminum was stably loaded on the PAC through facile solid-phase reaction between polymeric aluminum (polyaluminum chloride (PACl) or polyaluminum ferric chloride (PAFC)) and PAC (1:15 W/W). Fluoride adsorption on PACl and PAFC modified PAC (C-PACl and C-PAFC) all reached equilibrium within 5 min, at rate of 2.56 g mg-1 sec-1 and 1.31 g mg-1 sec-1 respectively. Larger increase of binding energy of Al on C-PACl (AlF bond: 76.64 eV and AlFOH bond: 77.70 eV) relative to that of Al on C-PAFC (AlF bond: 76.52 eV) explained higher fluoride uptake capacity of C-PACl. Less chloride was released from C-PACl than that from C-PAFC due to its higher proportion of covalent chlorine and lower proportion of ionic chlorine. The elements mapping and atomic composition proved the stability of Al loaded on the PAC as well as the enrichment of fluoride on both C-PACl and C-PAFC. The Bader charge, formation energy and bond length obtained from DFT computational results explained the fluoride adsorption mechanism further. The carbon emission was 7.73 kg CO2-eq/kg adsorbent prepared through mechanochemical process, which was as low as 1:82.3 to 1:8.07 × 104 compared with the ones prepared by conventional hydrothermal methods.

Impact of relaxing incisions on maxillofacial growth following Sommerlad-Furlow modified technique in patients with isolated cleft palate: a preliminary comparative study.

OBJECTIVE: To estimate the impact of relaxing incisions on maxillofacial growth following Sommerlad-Furlow modified technique in patients with isolated cleft palate. STUDY DESIGN: A Retrospective Cohort Study. METHODS: A total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate underwent primary palatoplasty (30 patients received the Sommerlad-Furlow modified technique without relaxing incision (S.F-RI group), and 30 received Sommerlad-Furlow modified technique with relaxing (S.F+RI group) with no significant difference found between them regarding the cleft type, cleft width, and age at repair. While the other 30 were healthy noncleft participants with skeletal class I pattern as a Control group. The control group (C group) was matched with the patient groups in number, age, and sex. All participants had lateral cephalometric radiographs at least 5 years old age. The lateral cephalometric radiographs were taken with the same equipment by the same experienced radiologist while the participants were in centric occlusion and a standardized upright position, with the transporionic axis and Frankfort horizontal plane parallel to the surface of the floor. A well-trained assessor (S. Elayah) used DOLPHIN Imaging Software to trace twice to eliminate measurement errors. All the study variables were measured using stable landmarks, including 12 linear and 10 angular variants. RESULTS: The mean age at collection of cephalograms was 6.03 ± 0.80 in the S.F+RI group, 5.96 ± 0.76 in the S.F-RI group, and 5.91 ± 0.87 in the C group. Regarding cranial base, the results showed no statistically significant differences between the three groups in S-N and S-N-Ba. While the S.F+R.I group had a significantly shortest S-Ba than the S.F-R.I & C groups (P = 0.01 & P < 0.01), but there was no statistically significant difference between S.F-R.I & C groups (P = 0.71). Regarding the skeletal maxilla, there was no significant difference between the S.F+R.I and S.F-R.I groups in all linear measurements (N-ANS and S-PM) except Co-A, the S.F+R.I group had significantly shorter Co-A than the S.F-R.I & C groups (P = < 0.01). While the angular measurement, S.F+R.I group had significantly less SNA angle than the S.F-R.I & C groups (P = < 0.01). Regarding mandibular bone, there were no statistically significant differences in all linear and angular mandibular measurements between the S.F+R.I and S.F-R.I.groups. Regarding intermaxillary relation, the S.F+R.I group had significant differences in Co-Gn-Co-A and ANB compared to the S.F-R.I & C groups (P = < 0.01). While there was no statistically significant difference in PP-MP between the three groups. CONCLUSION: As a preliminary report, the Sommerlad-Furlow modified technique without relaxing incisions was found to have a good maxillary positioning in the face and a satisfactory intermaxillary relationship compared to the Sommerlad-Furlow modified technique with relaxing incisions.

Size-Controlled Silver Nanoparticles Supported by Pyrolytic Carbon from Microcrystalline Cellulose.

A facile method was developed for preparing size-controlled silver nanoparticles supported by pyrolytic carbon from microcrystalline cellulose (MCC). The pyrolysis of cellulose-AgNO3 mixture caused the oxidation of cellulose, resulting in carboxyl groups to which silver ions can bind firmly and act as nuclei for the deposition of silver nanoparticles. The structure and properties of the obtained nanocomposite were characterized by using a scanning electron microscope (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). The results suggest that silver nanoparticles were integrated successfully and dispersed uniformly in the pyrolytic carbon matrix. The average particle size varied between 20 nm and 100 nm in correlation to the dose of silver nitrate and temperature of pyrolysis. The products showed high electric conductivity and strong antimicrobial activity against Escherichia coli (E. coli).

A comparison of maxillofacial growth in Chinese children with isolated cleft palate treated with two different palatoplasty techniques without relaxing incisions: a preliminary study.

OBJECTIVE: To assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified technique and compare it with the effect of the Sommerlad technique. STUDY DESIGN: A Retrospective Cohort Study. METHODS: A total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate (ISHCP) underwent primary palatoplasty without relaxing incision (30 patients received the Sommerlad-Furlow modified (S-F) technique and 30 received Sommerlad (S) technique). While the other 30 were healthy noncleft participants with skeletal class I pattern (C group). All participants had lateral cephalometric radiographs at least 5 years old age. All the study variables were measured by using stable landmarks, including 11 linear and 9 angular variants. RESULTS: The means age at collection of cephalograms were 6.03 ± 0.80 (5-7 yrs) in the S group, 5.96 ± 0.76 (5-7 yrs) in the S-F group, and 5.91 ± 0.87 (5-7 yrs) in the C group. Regarding cranial base, the results showed that there were no statistically significant differences between the three groups in S-N and S-N-Ba. The S group had a significantly shortest S-Ba than the S-F & C groups (P = 0.01), but there was no statistically significant difference between S-F and C groups (P = 0.80). Regarding skeletal maxillary growth, the S group had significantly shorter Co-A, S- PM and significantly less SNA angle than the C group (P = < 0.01). While there was no significant difference between S-F & C groups (P = 0.42). The S group had significantly more MP-SN inclination than the C group (P = < 0.01). Regarding skeletal mandibular growth, there were no statistically significant differences in all linear and angular mandibular measurements between the three groups, except Co-Gn of the S group had a significantly shorter length than the C group (P = 0.05). Regarding intermaxillary relation, the S-F group had no significant differences in Co-Gn-Co-A and ANB as compared with the C group. The S group had significantly less ANB angle than S-F & C groups (P = 0.01 & P = < 0.01). In addition, there were no significant differences in all angular occlusal measurements between the three groups. CONCLUSION: As a preliminary report, Sommerlad-Furlow modified technique showed that maxillary positioning in the face tended to be better, and the intermaxillary relationship was more satisfactory than that in Sommerlad technique when compared them in healthy noncleft participants.

Droplet size distribution, atomization mechanism and dynamics of dental aerosols.

Since the outbreak of COVID-19 pandemic, maintaining safety in dental operations has challenged health care providers and policy makers. Studies on dental aerosols often focus on bacterial viability or particle size measurements inside dental offices during and after dental procedures, which limits their conclusions to specific cases. Fundamental understanding on atomization mechanism and dynamics of dental aerosols are needed while assessing the risks. Most dental instruments feature a build-in atomizer. Dental aerosols that are produced by ultrasonic or rotary atomization are considered to pose the highest risks. In this work, we aimed to characterize dental aerosols produced by both methods, namely by Mectron PIEZOSURGERY® and KaVo EXPERTtorque™. Droplet size distributions and velocities were measured with a high-speed camera and a rail system. By fitting the data to probability density distributions and using empirical equations to predict droplet sizes, we were able to postulate the main factors that determine droplet sizes. Both dental instruments had wide size distributions including small droplets. Droplet size distribution changed based on operational parameters such as liquid flow rate or air pressure. With a larger fraction of small droplets, rotary atomization poses a higher risk. With the measured velocities reaching up to 5 m s-1, droplets can easily reach the dentist in a few seconds. Small droplets can evaporate completely before reaching the ground and can be suspended in the air for a long time. We suggest that relative humidity in dental offices are adjusted to 50% to prevent fast evaporation while maintaining comfort in the office. This can reduce the risk of disease transmission among patients. We recommend that dentists wear a face shield and N95/FFP2/KN95 masks instead of surgical masks. We believe that this work gives health-care professionals, policy makers and engineers who design dental instruments insights into a safer dental practice.

[Effect of Lipoteichoic Acid Synthesis-Related Gene dltD on Acid Tolerance of Highly Cariogenic Strains of Streptococcus mutans].

Objective: To study the role and possible mechanism of dltD in the acid tolerance of Streptococcus mutans 593 (SM593), and to provide a theoretical basis for the ecological prevention and control of dental caries by constructing the dltD gene deletion strain of SM593 (SM593-ΔdltD). Methods: 1) SM593-Δ dltD was constructed by homologous recombination. 2) The growth curve of SM593 dltD and SM593-Δ dltD under different pH culture conditions was drawn by the automatic growth curve analyzer to compare their acid tolerance. Colony forming unit (CFU) at different time points was used to calculate the survival rate and to compare the acid tolerance response (ATR) of SM593 and SM593-Δ dltD. 3) Under different pH conditions, glycolysis experiments, proton permeability test and H +-ATPase activity test were conducted to make preliminary exploration into the mechanisms of how dltD gene deletion may affect acid tolerance. Results: 1) PCR and sequencing results showed that the SM593-Δ dltD was constructed successfully. 2) With decreasing pH value of the culture medium, the growth of SM593-Δ dltD slowed down. When the pH value of the culture medium was 5.0, SM593-Δ dltD was not allowed to grow, and its acid tolerance was lower than that of SM593. Compared with SM593, the ATR capability of SM593-Δ dltD was decreased. 3) SM593 dltD and SM593-Δ dltD did not show obvious difference in their glycolysis ability under different pH conditions. Compared with SM593 dltD, the proton permeability of SM593-Δ dltD under different pH conditions was increased significantly (P<0.05), and H +-ATPase activity decreased significantly (P<0.05). Conclusion: Compared with SM593 dltD, SM593-Δ dltD showed obvious decrease in acid tolerance, which may be caused by the significant increase in proton permeability and significant decrease in the H +-ATPase activity induced by the deletion of the dltD gene, hence reducing its ability to maintain intracellular pH homeostasis.

"Bottom-Up" Assembly of Nanocellulose Microgels as Stabilizer for Pickering Foam Forming.

Microgels assembled from bio-based nanomaterials are a promising soft stabilizer for a Pickering system. In this study, nanocellulose microgels with foaming properties were constructed by electrostatic assembly between nisin and 2,2,6,6-tetramethyl piperidine-1-oxyl-oxidized cellulose nanocrystals (TOCNC). Pickering wet foam was prepared by using the microgels as a foaming stabilizer. Nanocellulose microgels exhibited better foaming ability and foam stability than TOCNCs. Quartz crystal microbalance with dissipation and transmission electron microscopy analyses confirmed that the nanocellulose microgels prepared under different nisin concentrations demonstrated significant differences in morphology, conformation, and structural strength. Microgel particles prepared at 0.03 and 0.06 wt % nisin concentrations had a unique dendritic microstructure. Microgels containing 0.06 wt % nisin displayed better foaming ability and foam stability. It was possible that the soft dendritic structure of the microgels could endow bubbles with sufficient thickness and strength to prevent coalescence. This novelty nanocellulose microgel is expected to be used for expanding the application of nanocellulose in the functional interfacial design of Pickering foams.

Imaging of the Silicone Implant with a 3D SPACE MR Sequence: The Accuracy for Estimating Implant Volume and Reconstructing Implant Deformation in Breast Surgery.

OBJECTIVE: The study is to assess the accuracy and reliability of 3D simulated magnetic resonance imaging with SPACE sequence for estimating implant volume and reconstructing implant deformation, which may assist in the diagnosis of implant complications and making individualized surgical plans for these patients. METHODS: MRI examinations of ten silicone implants were performed with T2, H2O-excitation SPACE sequence (T2-spc-H2O) and silicone-excitation SPACE sequence (T2-spc-Silicone) to find the most accurate method to estimate implant volume by ITK-SNAP. The effect of implant deformation and voxel size of silicone-excitation SPACE sequence on volume measurement was investigated. Thirteen normal patients and ten patients with implant complications (Wuhan Tongji Hospital from March 2017 to May 2019) were enrolled for testing the accuracy and reliability of 3D simulated MRI with silicone-excitation SPACE sequences for volume measurement and reconstructing implant deformation in patients. RESULTS: The absolute volume differences of T2-spc-Silicone group were significantly less than T2-spc-H2O and T2 group (6.28 vs. 23.27 vs. 42.19 mL, P < 0.05) in vitro. No significant difference was found between the normality group and the deformation group for estimating the volume of implants. Besides, the voxel size of T2-spc-Silicone from 0.5 × 0.5 × 0.5 mm to 5.0 × 5.0 × 5.0 mm did not significantly affect the accuracy of volume measurement of the implants in deformation state. However, 3D images of the implant became blurred with the voxel size increased. With the voxel size larger than 1.5 × 1.5 × 1.5 mm, the scores of image quality decreased significantly. The number of folds could not be identified accurately with the voxel size larger than 2.0 × 2.0 × 2.0 mm. In normal patients, the measurement errors of T2-spc-Silicone were around 10 mL. In the patients with implant complications, there was no significant difference between measured volume and the actual volume of implants. Moreover, implant deformations were clearly presented by T2-spc-Silicone with the voxel size of 1.0 × 1.0 × 1.0 mm. The results showed excellent intraobserver reliability (ICC = 0.997 > 0.8), and internal consistency ranged from 0.986 to 0.997 (P < 0.001). CONCLUSIONS: The method to measure implant volume by 3D simulated magnetic resonance imaging with T2-spc-Silicone sequence had possessed desirable accuracy and reliability. The deformation of the implant and the voxel size of the T2-spc-Silicone sequence didn't exhibit a significant effect on the accuracy of the measurement. T2-spc-Silicone with voxel size less than 2.0 × 2.0 × 2.0 mm could be used for 3D reconstruction of the implant deformation. The 1.0 × 1.0 × 1.0 mm was a suitable voxel size to reconstruct implant deformation clearly and quickly. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Influence of restorative material and cement on the stress distribution of endocrowns: 3D finite element analysis.

PURPOSE: This study aimed to evaluate the influence of different types of restorative materials and resin cements on the stress distribution in the regions of the restoration, cement layer and dental remnant in endodontically treated posterior endocrowns. METHODS: A 3D finite element analysis (FEA) model of the first mandibular molar that was restored with an endocrown designed by computer-aided design (CAD) software was generated. Three kinds of restorative materials (Vita Enamic (VE), IPS e.max CAD (EMX) and Grandio blocs (GR)) and two types of cementing materials (NX3 and Maxcem Elite Chroma (MX)) were analysed with such a model. The food layer was also designed before vertical (600 N) forces were applied to simulate physiological masticatory conditions. Thermal expansion was used to simulate the polymerization shrinkage effects of cement layers. The results were obtained by colorimetric graphs of the maximum principal stress in the restoration and tooth remnant. The failure risk of the cement layer was also calculated based on the normal stress. RESULTS: The elastic modulus was positively correlated with the tensile stress peak values in the restoration, mainly at the intaglio surface. However, in the cervical enamel and cement layer, restorative material with a higher elastic modulus generated lower peak stress values. The cement with a higher elastic modulus resulted in higher stress peak values inside the cement layer. The combination of EMX (restorative material) and NX3 (cement material) in the cement layer resulted in the lowest failure risk. SIGNIFICANCE: The ceramic material EMX with a higher elastic modulus appeared to be more effective at protecting the cement layer and residual enamel tissue. Based on the analysis of the failure risk of the cement layer, the combination of EMX and NX3 was recommended as an optional material for endocrowns for endodontically treated posterior teeth.

Decreasing acute toxicity and suppressing colorectal carcinoma using Sorafenib-loaded nanoparticles.

Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug.Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were evaluated and then their effects on the viability of colorectal cancer cells and normal human cells were assessed. The mechanism of S-NP internalization was explored using cellular uptake assays and in vitro fluorescence confocal imaging. Acute toxicity of sorafenib on its own or within S-NPs was assessed in mice.Results: S-NPs showed high drug loading and entrapment efficiencies, they did not cause extensive hemolysis, and they efficiently inhibited growth of colorectal cancer cell lines and human umbilical vein endothelial cells. S-NPs showed lower acute toxicity than the free drug.Conclusions: Loading sorafenib into nanoparticles can enhance its uptake by colorectal cancer cells and decrease its acute toxicity.

HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2.

Osteoporosis has been shown to intensify bone loss caused by periodontitis and both share common risk factors. One strategy utilized to manage the disease has been via the release of Sr ions by Strontium Ranelate having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously we have developed and characterized porous Sr-mesoporous bioactive glass (Sr-MBG) scaffolds and demonstrated their ability to promote periodontal regeneration when compared to MBG alone. Our group further discovered a splicing factor, heterogeneous nuclear ribonucleoprotein L (hnRNPL), was drastically down-regulated in periodontal ligament stem cells (PDLCs) stimulated by Sr through the activation of AKT pathway. Furthermore, hnRNPL restrained the osteogenic differentiation of PDLCs through down-regulating H3K36me3-specific methyltransferase Setd2. The goal of the present study was to investigate the mechanism of periodontal regeneration stimulated by Sr It was first found that the epigenetic mechanism of splicing factor hnRNPL participated in the osteogenesis processing of PDLCs stimulated by SrCl2 . Meanwhile, the different role of hnRNPL and SET domain containing 2 (Setd2) may provide some implication of the treatment of periodontitis patients simultaneously suffering from osteoporosis.

Magnetic Chip Based Extracorporeal Circulation: A New Tool for Circulating Tumor Cell in Vivo Detection.

In vivo detection of circulating tumor cells (CTCs) which inspect all of the circulating blood in body seems to have more advantages on cell capture, especially in earlier cancer diagnosis. Herein, based on in vivo microfluidic chip detection system (IV-chip-system), an extracorporeal circulation was constructed to effectively detect and monitor CTCs in vivo. Combined with microfluidic chip and immunomagnetic nanosphere (IMN), this system not only acts as a window for CTC monitoring but also serves as a collector for further cancer diagnosis and research on CTCs. Compared with the current in vivo detection method, this system can capture and detect CTCs in the bloodstream without any pretreatments, and it also has a higher CTC capture efficiency. It is worth mentioning that this system is stable and biocompatible without any irreversible damage to living animals. Taking use of this system, the mimicked CTC cleanup process in the blood vessel is monitored, which may open new insights in cancer research and early cancer diagnosis.

Detection of pesticide residues on intact tomatoes by carbon fiber ionization mass spectrometry.

Trace and toxic pesticide residues may still remain on crops after harvest. Thus, maximum residual levels (MRLs) of pesticides on crops have been regulated. To determine whether the remaining pesticide residue level is below MRL, time-consuming sample pretreatment is needed prior to analysis of crop samples by suitable analytical tools. By elimination of sample pretreatment steps, a high-throughput method can be developed to determine the presence of pesticide residues directly on intact crops. Carbon fiber ionization mass spectrometry (CFI-MS) is effective in determining analytes with different polarities in solid, liquid, and vapor phases in open air. Moreover, the vapor derived from solid or liquid samples possessing high vapor pressure can be readily detected by CFI-MS. The setup of CFI-MS is straightforward. A carbon fiber (diameter of ~ 10 µm and length of ~ 1 cm) is placed close (~ 1 mm) to the inlet of the mass spectrometer applied with a high voltage (- 4.5 kV). No direct electrical contact applied on the carbon fiber is required. When placing the sample with certain vapor pressure underneath the carbon fiber, analyte ions derived from the sample can be readily detected by the mass spectrometer. Given that most pesticides possess a certain vapor pressure (~ 1.33 × 10-5-~ 1.33 × 10-4 Pa), we herein develop a qualitative and quantitative analysis method to determine pesticide residues on intact fruits such as tomato based on CFI-MS without requiring any sample pretreatment. Atrazine, ametryn, carbofuran, chlorpyrifos, isoprocarb, and methomyl were selected as model samples. Low limits of detection (at nM range) were achieved for the model pesticides using the current approach. Moreover, we demonstrated that the precision and accuracy of quantitative analysis of ~ 5% and ~ 2%, respectively, could be achieved using this approach. Graphical Abstract ᅟ.

Leptin/OB-R signaling is elevated in mice with Sjögren's syndrome and is implicated in disease pathogenesis.

Sjögren's syndrome (SjS) is a systemic autoimmune disease resulting in a severe dry mouth and dry eyes. Currently, care for patients with SjS is palliative, as no established therapeutics target the disease directly, and its pathogenetic mechanisms are uncertain. Leptin activates B cells to induce the secretion of proinflammatory and anti-inflammatory cytokines and is elevated in several autoimmune diseases. In this study, we found the expression of leptin and its receptor OB-R in mouse models of SjS are elevated both locally and systemically during SjS progression. Recombinant serotype 2 adeno-associated viral (rAAV2) vectors expressing either OB-R shRNA (rAAV2-shOB-R) or none (rAAV2-null) were injected into 4 or 16 week-old BALB/c NOD/LtJ (NOD) mice and resulted in a modest reduction in glandular inflammation in the SjS model. In conclusion, Leptin/OB-R signaling may be pathogenically involved in SjS and may serve as a new marker and a potential therapeutic target.

Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

Tolerability, pharmacokinetics and antiviral activity of rHSA/IFNα2a for the treatment of chronic hepatitis B infection.

AIMS: A recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFNα2a) is expected to extend the half-life of IFNα2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFNα2a. METHODS: This is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naïve and non-cirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 µg of rHSA/IFNα2a or 180 µg of PEG-IFNα2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed. RESULTS: Thirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFNα2a treatment was better tolerated than the PEG-IFNα2a 180 µg treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life (t1/2 ) of rHSA/IFNα2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFNα2a 750 µg and PEG-IFNα2a 180 µg, with the exception of t1/2 , was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were -1.32, -2.13, -1.10 and -2.48 log10 IU/ml in the 600, 750 and 900 µg rHSA/IFNα2a groups and PEG-IFNα2a group, respectively. CONCLUSIONS: The rHSA/IFNα2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFNα2a and rHSA/IFNα2a 750 µg groups.

Association between Phthalate Exposure and the Use of Plastic Containers in Shanghai Adults.

OBJECTIVE: Consuming phthalates may be due to the presence of food contact materials, such as plastic containers. In this study, we investigated the association between plastic container use and phthalate exposure in 2,140 Shanghai adults. METHODS: Participants completed a questionnaire on the frequency of using plastic containers in different scenarios in the previous year (e.g., daily, weekly) and on the consumption of plastic-packaged foods in the previous three days (yes or no). Urinary phthalate metabolites were used to assess the association between phthalate exposure and the use of plastic containers. RESULTS: The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the most frequently detected in urine. The results revealed that phthalate exposure was associated with consumption of plastic-packaged breakfast or processed food items in the previous three days. The consumption of these two food items had strong synergistic effects on increasing urinary concentrations of most phthalate metabolites. CONCLUSION: Our results of plastic-packaged breakfast and processed food may be explained by the use of flexible plastic containers, indicating the importance of risk assessment for the application of flexible plastic containers.

[Inhibition of transformation from puerarin monohydrate to puerarin dihydrate by polyvinylpyrrolidones during dissolution].

Puerarin (PUE), an isoflavone with anti-inflammation, anti-oxidation and neuroprotection effects, has been widely applied to the treatment of cardiovascular diseases in clinics in China. In the current study, we reported that the active pharmaceutical ingredient (API) of marketed products was the PUE monohydrate (PUEMH). During its supersaturated dissolution, the PUE concentration quickly reached a plateau, followed by a gradually concentration decrease to another lower plateau. In order to explore the internal mechanism of above phenomenon, the solid residues after saturated dissolution test were characterized by powder X-ray diffraction (PXRD), thermal gravity analysis (TGA) and Karl Fisher titration (KFT). PXRD suggested that a novel PUE crystal different from PUEMH formed during its dissolution, the following TGA and KFT confirmed the generation of PUE dihydrate (PUEDH) with much lower solubility. Moreover, polyvinylpyrrolidones (PVPK12, PVPK30 and PVPK90) were added in the dissolution medium to investigate their potential inhibition effects on such crystal transformation during dissolution process. We observed that polymers could inhibit the transformation from PUEMH to PUEDH and result in much higher PUE concentration level than that in pure water.

Sex Hormones Enhance Gingival Inflammation without Affecting IL-1ß and TNF-α in Periodontally Healthy Women during Pregnancy.

Hormones (progesterone and estradiol) change greatly during pregnancy; however, the mechanism of hormonal changes on gingival inflammation is still unclear. This study is to evaluate the effects of hormonal changes during pregnancy on gingival inflammation and interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant women were evaluated in the first, second, and third trimesters. 20 periodontally healthy nonpregnant women were evaluated twice (once per subsequent month). Clinical parameters including probing pocket depth (PPD), bleeding index (BI), gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were recorded. GCF levels of IL-1ß and TNF-α and serum levels of progesterone and estradiol were measured. From the data, despite low PLI, BI and GI increased significantly during pregnancy; however, no significant changes in PLI, CAL, IL-1ß, or TNF-α GCF levels were observed. Although IL-1ß, not TNF-α, was higher in pregnant group than in nonpregnant group, they showed no correlation with serum hormone levels during pregnancy. GI and BI showed significant positive correlation with serum hormone levels during pregnancy. This study suggests that sex hormone increase during pregnancy might have an effect on inflammatory status of gingiva, independent of IL-1ß and TNF-α in GCF.