Biocompatible orthodontic cement with antibacterial capability and protein repellency.

BACKGROUND: White spot lesions (WSLs) often occur in orthodontic treatments. The objectives of this study were to develop a novel orthodontic cement using particles of nano silver (NAg), N-acetylcysteine (NAC) and 2-methacryloyloxyethyl phosphorylcholine (MPC), and to investigate the effects on bonding strength, biofilms and biocompatibility. METHODS: A commercial resin-modified glass ionomer cement (RMGIC) was modified by adding NAg, NAC and MPC. The unmodified RMGIC served as the control. Enamel bond strength and cytotoxicity of the cements were investigated. The protein repellent behavior of cements was also evaluated. The metabolic assay, lactic acid production assay and colony-forming unit assay of biofilms were used to determine the antibacterial capability of cements. RESULTS: The new bioactive cement with NAg, NAC and MPC had clinically acceptable bond strength and biocompatibility. Compared to commercial control, the new cement suppressed metabolic activity and lactic acid production of biofilms by 59.03% and 70.02% respectively (p < 0.05), reduced biofilm CFU by 2 logs (p < 0.05) and reduced protein adsorption by 76.87% (p < 0.05). CONCLUSIONS: The new cement with NAg, NAC and MPC had strong antibacterial capability, protein-repellent ability and acceptable biocompatibility. The new cement is promising to protect enamel from demineralization during orthodontic treatments.

Combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase (GDP-ML) for patients with newly diagnosed extranodal natural killer/T cell lymphoma, nasal type: a single arm, single center, prospective phase 2 study.

Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p < 0.001). Patients who achieved CR had significantly better 2-year OS rate compared with non-CR patients (90.8% vs. 24.5%, p < 0.001). The main adverse event was hematologic toxicity. Grade 3/4 neutropenia occurred in 59.1% of patients. These results indicate that GDP-ML is an effective and well-tolerated induction regimen with newly diagnosed ENKL patients. This clinical trial was registered on www.chictr.org.cn (ChiCTR-ONC-12002055).

Polymerization-Induced Self-Assembly to Produce Prodrug Nanoparticles with Reduction-Responsive Camptothecin Release and pH-Responsive Charge-Reversible Property.

Polymerization-induced self-assembly has been demonstrated to be a powerful strategy for fabricating polymeric nanoparticles in the last two decades. However, the stringent requirements for the monomers greatly limit the chemical versatility of PISA-based functional nanoparticles and expanding the monomer family of PISA is still highly desirable. Herein, a camptothecin analogue (CPTM) is first used as the monomer in PISA. Prodrug nanoparticles with reduction-responsive camptothecin release behavior are fabricated at 10% solid concentration (100 mg g-1 ). Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) are used as the macro RAFT agents to comediate the RAFT dispersion polymerization of CPTM in ethanol to produce the PHPMA/PDEAEMA-stabilized nanoparticles. The PDEAEMA chains become hydrophobic and are in the collapsed state at physiological pH values. In contrast, in the vicinity of an acidic tumor, the tertiary amine groups of PDEAEMA chains are rapidly protonated, leading to fast hydrophobic-hydrophilic transitions and charge reversal. Such fast charge-reversal results in enhanced cancer cell internalization of the prodrug nanoparticles, thus achieving superior anticancer efficacy.

Long-Term Taste Impairment after Intensity-Modulated Radiotherapy to Treat Head-and-Neck Cancer: Correlations with Glossectomy and the Mean Radiation Dose to the Oral Cavity.

We explored the effects of various parameters on taste impairments (TIs) in head-and-neck (H&N) cancer patients receiving intensity-modulated radiotherapy (IMRT). From January 2014 to September 2017, 88 H&N cancer patients subjected to curative or postoperative IMRT were enrolled in this prospective study. All patients underwent at least 1 year of follow-up after IMRT. Quality-of-life assessments in terms of patient-reported gustatory function were measured using the taste-related questions of the European Organization for Research and Treatment of Cancer H&N35 questionnaires. At a median follow-up time of 27 months, 27 of 88 patients (30.7%) reported long-term TIs. In multivariate analyses, glossectomy most significantly predicted TIs (P = 0.04). The percentage of TIs (61.5%) was significantly (P = 0.03) higher in patients who underwent partial or total glossectomy than in patients who did not undergo surgery (28.0%) and those who underwent radical surgery without glossectomy (20.0%). When we excluded surgical patients from analyses, the mean radiation dose to the oral cavity was of borderline significance in terms of TI prediction (P = 0.05). Only 10.5% of patients suffered from TIs when the mean radiation dose was <5000 cGy compared with 38.7% when the mean dose was ≥5000 cGy. In conclusion, glossectomy is the major cause of long-term TIs in H&N cancer patients receiving IMRT. In patients who do not undergo glossectomy, reduction of the mean radiation dose to the oral cavity may reduce TIs after IMRT.

Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate and pegaspargase is active in newly diagnosed peripheral T cell lymphoma patients: a phase 2, single-center, open-label study in China.

Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244.

Polymer microfiber meshes facilitate cardiac differentiation of c-kit(+) human cardiac stem cells.

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit(+) human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5µm) elastomeric meshes consisting of aligned 1.7µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases.

[Syndrome Features of Chinese Medicine in Hyperlipidemia Patients of Han, Uyghur, Kazakh Na- tionalities in Xinjiang Uyghur Autonomous Region].

Objective To observe distribution laws and features of syndrome types of Chinese medicine (CM) in hyperlipidemia patients of Han, Uyghur, Kazakh nationalities in Xinjiang Uyghur Auton- omous Region. Methods Using cluster random sampling, 1 410 hyperlipidemia patients (18 -70 years old ) were recruited from Urumqi, Turpan, Altay, Ili, Aksu, Hetian in Xinjiang Uyghur Autonomous Re- gion. The general condition, susceptible factors, classification of blood lipids, complications, syndromes of CM, tongue figure, etc. clinical data were investigated using self-formulated Epidemiological Investiga- tion Questionnaire on Susceptible Factors in Different Nationalities of Hyperlipemia Patients in Xinjiang (abbreviated as Questionnaire thereafter). Factor analysis and cluster analysis were performed. Results Cronbach's coefficient for the 54 syndrome items in Questionnaire was 0.891, Kaiser-Meyer-Olkin (KMO) 0. 897, Sig <0.05 in Bartlett's sphericity test. Seventeen common factors were obtained using principal component analysis (PCA). Totally 54 common symptoms of hyperlipidemia were screened, which were then divided into 17 groups with 1 -6 symptoms in each group. F4 (soreness and weakness of waist and knees, sour pain in joints and muscles, body numbness, heavy body sensation, cold limbs), F5 (frequent and clear nocturia, dysuria,-dribble of urine, frequent urination at night), F10 (thirsty, no desire for water, tastelessness, hydroadipsia) , F12 (a white complexion with puffiness, hid- ing fever, hypoactive sexual desire) , and F17 (enuresis) were merged as Shen yang deficiency (SYD) ; F2 (fatigue, drowsiness, depression, spiritlessness, fatigue and disinclination to talk) and F15 (poor ap- petite) were merged as Pi-qi deficiency (PQD) ; F3 (dry mouth and dry pharynx, thirsty, propensity for water, bitter mouth, greasy mouth, stingy mouth, irritability and upset) and F16 (dark red tongue proper, greasy tongue fur) were merged as damp-heat trapped in Pi (DHTP). Results of cluster analysis showed that Pi-Shen deficiency (PSD) was most often seen in hyperlipidemia, and main syndrome types were sequenced from high to low as Pi-Shen deficiency type (46. 2%, 652/1 410) , blockage of cardiac vessels type ( 31. 1% , 438/1 410 ), phlegm and blood stasis internal resistance type ( 13. 3% , 187/1 410), Pi-deficiency induced damp abundance type (8. 3%, 123/1 410), Gan-Shen yin deficiency type (0. 7%, 10/1 410). Conclusions Deficiency syndrome was dominant in hyperlipidemia patients of Xinjiang Uyghur Autonomous Region. Phlegm turbidity, damp heat, and etc. were often complicated. The complex situation was manifested to be involved in multiple organs, qi-blood-fluid mixed disease.

Releasing characteristics of toxic chemicals from polystyrene microplastics in the aqueous environment during photoaging process.

Microplastics (MPs) are pervasive in the environment and inevitably undergo photoaging due to UV irradiation. This study delved into the dynamic releasing and transformation process of toxic chemicals from polystyrene microplastics (PS MPs) during photoaging, a subject that remains underexplored. It was revealed that photoaging led to substantial alterations in the physicochemical properties of PS MPs, initiating polymer chain scission and facilitating the release of a large number of toxic chemicals, including numerous organic compounds and several inorganic compounds. The kinetic analysis revealed a dynamic release pattern for PS MPs, where under varying UV intensities (2, 5, and 10 mW/cm2), the release rate (kDOC) initially increased and then decreased, peaking at a total irradiation energy of approximately 7 kW·h/m2. Furthermore, chemicals in leachate were transformed into compounds with smaller molecular weight, higher oxidized and greater unsaturated state over the prolonged photoaging. This transformation was primarily attributed to two reasons. Firstly, the aged PS MPs released chemicals with higher oxidized state compared to the pristine MPs. Secondly, the chemicals previously released underwent further reactions. Besides, among the complex leachate generated by aged PS MPs, the organic chemicals characterized by small molecular weight and high oxidized state exhibited notable acute toxicity, whereas heavy metal ions showed lesser toxicity, and anions were non-toxic. This study shed more light on the photoaging process of PS MPs, releasing characteristics of organic chemicals, and the potential environmental risks associated with plastic wastes.

Effect of biodegradable PBAT microplastics on the C and N accumulation of functional organic pools in tropical latosol.

Microplastics (MPs) pollution is becoming an emerging global stressor for soil ecosystems. However, studies on the impacts of biodegradable MPs on soil C sequestration have been mainly based on bulk C quantity, without considering the storage form of C, its persistency and N demand. To address this issue, the common poly (butylene adipate-co-terephthalate) (PBAT) was used as the model, and its effects on soil functional organic pools, including mineral-associated (MAOM), particulate (POM) and dissolved organic matter (DOM), were investigated from the novel coupled perspective of C and N stocks. After adding PBAT-MPs, the contents of soil POM-C, DOM-C, and MAOM-C were increased by 546.9 %-697.8 %, 54.2 %-90.3 %, and 13.7 %-18.9 %, respectively. Accordingly, the total C increased by 116.0 %-191.1 %. Structural equation modeling showed that soil C pools were regulated by PBAT input and microbial metabolism associated with C and N enzymes. Specifically, PBAT debris could be disguised as soil C to promote POM formation, which was the main pathway for C accumulation. Inversely, the MAOM-C and DOM-C formation was attributed to the PBAT microbial product and the selective consumption in DOM-N. Random forest model confirmed that N-activated (e.g., Nitrospirae) and PBAT-degrading bacteria (e.g., Gemmatinadetes) were important taxa for soil C accumulation, and the key enzymes were rhizopus oryzae lipas, invertase, and ammonia monooxygenase. The soil N accumulation was mainly related to the oligotrophic taxa (e.g., Chloroflexi and Ascomycota) associated with aggregate formation, decreasing the DOM-N by 46.9 %-84.3 %, but did not significantly change the total N storage and other N pools. Collectively, the findings highlight the urgency to control the nutrient imbalance risk of labile N loss and recalcitrant C enrichment in POM to avoid the depressed turnover rate of organic matter in MPs-polluted soil.

Effects of polypropylene microplastics on carbon dioxide dynamics in intertidal mangrove sediments.

Microplastics (MPs) in soil can influence CO2 dynamics by altering organic carbon (OC) and microbial composition. Nevertheless, the fluctuation of CO2 response attributed to MPs in mangrove sediments is unclear. This study explores the impact of micro-sized polypropylene (mPP) particles on the carbon dynamics of intertidal mangrove sediments. In the high-tide level sediment, after 28 days, the cumulative CO2 levels for varying mPP dosages were as follows: 496.86 ± 2.07, 430.38 ± 3.84 and 447.09 ± 1.72 mg kg-1 for 0.1%, 1% and 10% (w/w) mPP, respectively. The CO2 emissions were found to be increased with a 0.1% (w/w) mPP level and decreased with 1% and 10% (w/w) mPP at high-tide level sediment, suggesting a tide level-specific dose dependence of the CO2 emission pattern in mangrove sediments. Overall, results indicated that the presence of mPP in mangrove sediments would potentially affect intertidal total CO2 storage under given experimental conditions.

Molecular insights into effects of PBAT microplastics on latosol microbial diversity and DOM chemodiversity.

The impact of biodegradable microplastics on the microbial community and dissolved organic matter (DOM) in latosol has not been well reported. In this study, an incubation experiment at 25 ºC for 120 days using latosol amended with low (5%) and high (10%) concentrations of polybutylene adipate terephthalate (PBAT) microplastics was carried out to explore the impacts of PBAT microplastics on soil microbial communities and DOM chemodiversity, and the intrinsic interactions between their shifts. The main bacterial and fungal phyla in soil, namely Chloroflexi, Actinobacteria, Chytridiomycota, and Rozellomycota showed a nonlinear relationship with PBAT concentration and played a pivotal role in shaping DOM chemodiversity. A higher decreased levels of lignin-like compounds and increased levels of protein-like and condensed aromatic compounds in the 5% treatment were observed than that in the 10% treatment. Furthermore, a higher increase relative abundance of CHO compounds in the 5% treatment than in the 10% treatment was ascribed to its higher oxidation degree. Co-occurrence network analysis suggested that bacteria formed more complex relationships with DOM molecules than fungi did, indicating their critical roles in DOM transformation. Our study has important implications for understanding the potential influence of biodegradable microplastics on carbon biogeochemical roles in soil.

Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

Background and purpose: This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Materials and methods: Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs. ≥ 5 mm) and different adjuvant treatments (RT vs. CCRT). Results: Median follow-up time, age, and invasion depth were 88.5 months, 57 years, and 14 mm, respectively. More patients undergoing adjuvant CCRT had surgical margins < 5 mm (47.6% vs. 21.5%, p < 0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins ≥ 5 mm, worse LRRFS trends were observed in patients with surgical margins < 5 mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p = 0.06). Conclusion: Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins < 5 mm.

Environmental behaviors and degradation methods of microplastics in different environmental media.

Microplastics, as a group of emerging contaminants, are widely present in environmental media and have the potential to endanger the ecological environment and human health. Due to the inconsistencies and difficulties inherent in the analysis of microplastic particles, global monitoring data on the distribution of microplastics in the environment are still far from sufficient. The fate and migration of microplastics in the environment are also uncertain. Therefore, there have been increasing reviews on the distribution, biological effects, migration, and health risks of microplastics. However, reports focusing on the degradation of microplastics are still rare. Understanding and commanding the environmental behavior of microplastics are of great significance to explore the treatment of microplastic pollution. Although some preliminary studies on microplastics have been carried out, there is still an urgent need to conduct a comprehensive study on environmental behaviors and degradation methods of microplastics in different environmental media. This article summarizes the recent advances on microplastics, basically includes the distribution and ecological impact of microplastics in soil and water environments, then elaborates the migration behavior and influencing factors of microplastics, and focuses on the research progress of microplastics degradation methods. On this basis, the problems existing in the current research and the future development directions have been proposed. This review could provide a more systematic reference for the development and research of microplastics in the future.

Addition of biodegradable microplastics alters the quantity and chemodiversity of dissolved organic matter in latosol.

Dissolved organic matter (DOM) chemodiversity plays an important role in regulating nutrient cycles and contaminant behavior in soil. However, how biodegradable microplastic (MPs) affect the DOM chemodiversity is still unknown, although developing biodegradable plastics are regarded as a promising strategy to minimize the risks of MPs residues in soil. Here, with the common poly (butylene adipate-co-terephthalate) (PBAT) as the model, the molecular effect of biodegradable MPs on soil DOM was explored by adding 0%, 5% and 10% (w/w) of PBAT to tropical latosol, respectively. The results showed that PBAT addition increased microbial activity and exoenzyme activity (e.g., rhizopus oryzae lipase, invertase and cellulose). As a result, the quantity and chemodiversity of soil DOM were changed. The multispectroscopic characterization showed that PBAT addition significantly increased the DOC molecules in soil, including condensed aromatic-like substances and carbohydrates. In contrast, the TDN molecules with high bioavailability and low aromaticity, such as amino acids, were decreased. The multivariate statistical analysis indicated that there were three mechanisms that drove the shift in DOM chemodiversity. Firstly, the degradation of PBAT by rhizopus oryzae lipase facilitated the release of exogenous aromatic molecules. Secondly, PBAT decomposition stimulated the selective consumption of native N-rich molecules by soil microbes. Thirdly, PBAT accelerated the enzymatic transformation of native aliphatic CHx and cellulose toward humic substances. In addition, concentration effect was also observed in the study that high-concentration PBAT were more likely to trigger the molecular shift in DOM chemodiversity. These findings provided a new insight into the impact of biodegradable MPs on soil DOM chemodiversity at molecular level, which will be beneficial to understanding the fate and biochemical reactivity of DOM in MPs-polluted soil.

Ultrasound and magnetic resonance imaging of cyclic arginine glycine aspartic acid-gadopentetic acid-polylactic acid in human breast cancer by targeting αvß3 in xenograft-bearing nude mice.

Effective early detection shows the potential to reduce breast cancer mortality. This study aimed to establish a targeted contrast agent for Magnetic Resonance Imaging (MRI)/ultrasound dual-modality molecular radiography for breast cancer. The cyclic arginine-glycine-aspartate-gadopentetic acid-polylactic acid (cRGD and Gd-DTPA) coated by multi-functional blank poly (lactic-co-glycolic acid) (PLGA) nanoparticles) was successfully constructed by chemical synthesis method with high stability. The safety of cRGD-Gd-DTPA-PLGA was demonstrated in vitro and in vivo, and their affinity to breast cancer cells was revealed. Moreover, MRI/ultrasound dual-modality molecular radiography in vitro showed that as the concentration of contrast agent increased, the echo enhancement and signal intensity of MRI imaging were also elevated. The mouse models of human breast cancer also indicated significant target enhancements of cRGD-Gd-DTPA-PLGA magnetic nanoparticles in the mouse tumor. Thus, cRGD-Gd-DTPA-PLGA magnetic nanoparticles were suggested as qualified MRI/ultrasound dual-modality molecular radiography contrast agent. We further explored the targeting mechanism of cRGD-Gd-DTPA-PLGA in breast cancer. The results showed that αvß3 was highly expressed in breast cancer tissues, and cRGD-Gd-DTPA-PLGA used for MRI/ultrasound dual-modality molecular radiography by targeting αvß3. Additionally, we found that the signal-to-noise ratio of MRI was positively correlated with microvessel density (MVD). The cRGD-Gd-DTPA-PLGA dynamicly and quantitatively monitored breast cancer by monitoring the state of neovascularization. In conclusion, in the present study, we successfully constructed the cRGD-Gd-DTPA-PLGA magnetic nanoparticles for MRI/ultrasound dual-modality molecular radiography. The cRGD-Gd-DTPA-PLGA showed potential in early detection and diagnosis of metastasis, and dynamic evaluation of the efficacy of molecular targeted therapy of integrin αvß3.

Fertilization regime shifts the molecular diversity and chlorine reactivity of soil dissolved organic matter from tropical croplands.

Soil-derived dissolved organic matter (SDOM) is an important site-specific disinfection byproduct (DBP) precursor in watersheds. However, it remains unclear how fertilization regime shifts the molecular diversity and chlorine reactivity of SDOM in cropland-impacted watersheds. Here, we analyzed the spectroscopic and molecular-level characteristics of the SDOM from croplands that had different fertilization regimes (i.e., non-fertilization, chemical fertilization, straw return, and chemical fertilization plus straw return) for 5 years and evaluated the chlorine reactivity of the SDOM by determining the 24-h chlorine consumption and specific DBP formation potential (SDBP-FP). The SDOM level decreased by chemical fertilization and was not significantly altered by straw return alone or combined with chemical fertilizer. However, all fertilization regimes elevated the molecular diversity of SDOM by increasing the abundance of protein-, lignin-, and tannin-like compounds. The chlorine reactivity of SDOM was reduced by chemical fertilization, but was significantly increased by straw return. Typically, straw return increased the formation potential of specific trihalomethane and chloral hydrate by 339% and 56% via increasing the aromatics in SDOM, whereas chemical fertilization could effectively decrease about 231% of the increased specific trihalomethane formation potential caused by straw return. This study highlights that fertilization regime can significantly shape the molecular diversity and chlorine reactivity of the SDOM in croplands and that partially replacing chemical fertilizer with crop straw is an advantageous practice for reducing DBP risks in drinking water in cropland-impacted watersheds.

Prospective Evaluation of Taste Function in Patients With Head and Neck Cancer Receiving Intensity-Modulated Radiotherapy.

Importance: The majority of the patients with head and neck cancer (HNC) experience taste dysfunction (TD) during or after radiotherapy (RT). However, prospectively collected data for taste dysfunction have been limited, especially in the era of intensity-modulated RT (IMRT). Objective: To evaluate the taste function in patients with HNC receiving IMRT by investigating the association between time course and recovery of TD in both acute and late phases. Design, Setting, and Participants: From August 2017 to November 2020, patients treated at the Chang Gung Memorial Hospital with curative or postoperative IMRT for HNC were enrolled in this prospective cohort study. The data analysis was performed from March 2021 to January 2022. Exposures: IMRT with and without concurrent chemotherapy. Main Outcomes and Measures: Taste function was measured using the whole-mouth solution method for 4 tastes (salt, sweet, sour, and bitter). Subjective evaluations (National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03] and Subjective Total Taste Acuity scale) were used. Patient self-reported quality of life was evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35). Results: A total of 87 patients (78 [90%] men and 9 [10%] women; mean [range] age, 58 [31-80] years) were enrolled. Overall TD rates were 79 of 86 (91.9%), 63 of 83 (75.9%), 27 of 81 (33.3%), 5 of 56 (8.9%), and 2 of 30 (6.7%) during RT, and 1 week, 3 months, 6 months, and 1 year after RT, respectively. Positive correlation occurred between objectively measured taste loss for the 4 taste qualities and subjective perception of taste loss. Only oral cavity mean dose 4000 cGy or greater predicted TD 3 months after RT. The mean oral cavity doses to the predicted 15% (D15), 25% (D25), and 50% (D50) probabilities were 25, 38, and 60 Gy at 3 months and 57, 60, and 64 Gy at 6 months, respectively. Conclusions and Relevance: In this cohort study, most patients still experienced TD during and at 3 months after RT. Only a few patients experienced long-term TD. A high oral cavity dose was associated with TD in patients with HNC receiving IMRT. Reducing oral cavity dose may promote early recovery of taste function after IMRT.

The effect of N-acetylcysteine on the antibacterial capability and biocompatibility of nano silver-containing orthodontic cement.

OBJECTIVES: To determine whether the incorporation of N-acetylcysteine (NAC) improves the antibacterial ability and biocompatibility of nano silver (NAg)-containing orthodontic cement. MATERIALS AND METHODS: NAg was synthesized using a sodium citrate reduction method. NAg particles were characterized using transmission electron microscopy and ultraviolet-visible absorption spectra. NAg and NAC were incorporated into a resin-modified glass ionomer cement. Enamel shear bond strength (SBS), antibacterial capability, and cytotoxicity were evaluated. RESULTS: Incorporating 0.15% NAg and 20% NAC had no adverse effect on the SBS of orthodontic cement (P > .1). Adding NAC into NAg-containing cement greatly reduced the biofilm metabolic activity and lactic acid production (P < .05) and lowered the colony unit-forming counts by approximately 1 log (P < .05). The cell viability against NAg-containing cement was improved by NAC (P < .05). CONCLUSIONS: The incorporation of NAC into NAg-containing cement achieved stronger antibacterial capability and better biocompatibility, without compromising the enamel SBS. The combined use of NAC and NAg is promising to combat caries in orthodontic practice.

Survival-Weighted Health Profiles in Nasopharyngeal Cancer Patients.

INTRODUCTION: In treating nasopharyngeal cancer (NPC) patients, excellent tumor control and patient survival rates can be achieved in the era of intensity-modulated radiotherapy (IMRT). However, treatment-related toxicities affect the quality of life (QoL) of NPC survivors. This study was devised to estimate the life expectancy (LE), quality-adjusted life expectancy (QALE) and survival-weighted psychometric scores (SWPS) in NPC patients. METHODS: A sample of 875 non-metastatic NPC patients diagnosed between January 1, 2009 and June 30, 2013 was collected for estimation of lifetime survival function. All patients were followed up until death or censored on December 31, 2015. To obtain the utility and psychometric score for estimation of LE, QALE, and SWPS, 99 patients were measured with the Taiwanese version of the EuroQol instrument (EQ-5D) and the Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-H&N35 between October 1, 2013 and December 31, 2017. By utilizing linear extrapolation of a logit-transformed curve, the LE of NPC patients can be estimated. The QALE and SWPS can be obtained by combining the LE and the corresponding QOL function. RESULTS: The mean age of the 875 non-metastatic NPC patients was 50.3 years. The estimated average LE and QALE for NPC patients and for the reference population were 15.5 years and 14.3 quality-adjusted life years (QALYs) and 29.5 years and 29.5 QALYs, respectively. On average, the estimated lifelong duration of pain and painkiller use were 6.0 years and 2.2 years. The estimated lifelong duration of impairment of swallowing, speech, smell and taste were 14.0, 9.8, 8.7, and 7.5 years, respectively. The estimated lifelong duration of problems with dry mouth, teeth, emotion, fatigue, sleep, and social contact were 13.4, 10.1, 9.1, 12.3, 6.7, and 4.5 years, respectively. The estimated lifelong duration of tube-feeding was 1.3 months. CONCLUSIONS: The estimated LE and QALE for NPC patients were 15.5 years and 14.3 QALYs. Furthermore, SWPS could help people understand more about the impact of radiotherapy on NPC patients. These data could also be useful for policy makers to allocate limited resources in health care.

Porphyromonas gingivalis promotes tumor progression in esophageal squamous cell carcinoma.

PURPOSE: Increasing evidence indicates that the microbiome may influence tumor growth and modulate the tumor microenvironment of gastrointestinal cancers. However, the role of oral bacteria in the development of esophageal squamous cell carcinoma (EsoSCC) has remained unclear. Herein, we investigated the relationship between the periodontal pathogen Porphyromonas gingivalis and EsoSCC. METHODS: To identify bacterial biomarkers associated with EsoSCC, we analyzed microbiomes in oral biofilms. The presence of P. gingivalis in esophageal tissues and relationships of P. gingivalis infection with clinicopathologic characteristics in 156 patients with EsoSCC were assessed using immunohistochemistry. The role of P. gingivalis infection in in vitro and in vivo EsoSCC progression was also assessed. RESULTS: Microbiota profiles in oral biofilms revealed that P. gingivalis abundance was associated with an increased risk of EsoSCC development. In total, 57% of patients with EsoSCC were found to be infected with P. gingivalis. The presence of P. gingivalis was found to be associated with advanced clinical stages and a poor prognosis. It was also found to be associated with an elevated esophageal cancer incidence in a 4-nitroquinoline 1-oxide-induced mouse model and with an increased xenograft tumor growth. P. gingivalis infection increased interleukin (IL)-6 production and it promoted epithelial-mesenchymal transition and the recruitment of myeloid-derived suppressor cells. Furthermore, inhibited IL-6 signaling attenuated the tumor-promoting effects of P. gingivalis in 4-nitroquinoline 1-oxide-treated mice and xenograft mouse models. CONCLUSIONS: Our data indicate that P. gingivalis may promote esophageal cancer development and progression. Direct targeting of P. gingivalis or concomitant IL-6 signaling may be a promising strategy to prevent and/or treat EsoSCC associated with P. gingivalis infection.