Identification of degradation products of brivaracetam using liquid chromatography quadrupole time-of-flight tandem mass spectrometry: Degradation pathway elucidation.

RATIONALE: Pyrrolidone-based drugs find widespread use in treating conditions such as epilepsy and Alzheimer's disease, and in various other medical applications. Brivaracetam, the latest generation of pyrrolidone drugs, has exhibited significant promise owing to chemical structure modifications. Its affinity to the SV2A receptor is double that of the previous-generation drug, levetiracetam. Consequently, brivaracetam holds substantial potential for diverse applications. As a novel drug not yet included in the pharmacopeias of developed nations, comprehensive analysis and research are necessary to guarantee its safe utilization in clinical settings. METHODS: A liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC/QTOFMS) method has been developed to effectively separate, identify and characterize both the degradation products and process-related substances of brivaracetam. Stress testing of the sample was carried out following the guidelines outlined in ICH Q1A(R2). The structures of these impurities were identified through positive electrospray ionization QTOF high-resolution MS and NMR spectroscopy. Additionally, the formation mechanism of each degradation product is thoroughly discussed. RESULTS: Under the analytical conditions outlined in this paper, brivaracetam and its degradation products were effectively separated. Thirteen degradation products were detected and characterized, shedding light on their origins and degradation pathways. Among these, three degradation products align with previously reported impurities, and two unreported degradation products were synthesized and confirmed through NMR spectroscopy. The stress testing results revealed the instability of brivaracetam under acidic, alkaline, oxidative and thermal stress conditions, while it exhibited relative stability under photolytic stress conditions. CONCLUSION: The study developed an analytical method for brivaracetam that enabled the effective detection and separation of brivaracetam and its 13 degradation products. This method addresses a gap in both current domestic and foreign drug standards. The structures of all the major degradation products were characterized by high-resolution LC/QTOFMS, which is essential for quality control during the drug production process, stability evaluation and the establishment of proper storage conditions.

Association between dental visit behavior and mortality: a nationwide longitudinal cohort study from NHANES.

OBJECTIVES: The benefits of professional dental treatment for oral diseases have been widely investigated. However, it is unclear whether professional dental treatment provides additional benefits for improving general health. MATERIALS AND METHODS: Data were obtained from the US National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 and 2011 to 2018 cycles. A total of 36,174 participants were included and followed-up for mortality until December 31, 2019. Dental visit behavior was defined as the time interval of last dental visit (TIDV, < 0.5 year, 0.5-1 year, 1-2 years, 2-5 years, and > 5 years) and the main reasons of the last dental visit (treatment, examination, and other reasons). The Cox proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with participants with time interval of less than 0.5 year, the multivariate-adjusted HRs and 95%CI for participants with time interval of more than 5 years were 1.45 (1.31, 1.61) for all-cause mortality (P trend < 0.0001), 1.49 (1.23, 1.80) for cardiovascular diseases mortality (P trend = 0.0009) and 1.53 (1.29, 1.81) for cancer mortality (P trend = 0.013). Compared with dental visit for examination, participants who had their dental visit for treatment had higher risk for mortality. For participants with dental visit for examination, TIDV of less than 1 year showed lower risk for mortality, whereas TIDV of less than 0.5 year is recommend for population with dental visit for treatment. CONCLUSIONS: Poor dental visit behavior is associated with an increased risk of mortality. Further well-designed studies are needed to confirm the association between professional dental visit and mortality. CLINICAL RELEVANCE: This study highlights the potential benefits of regular dental visits in maintaining general health.

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES.

BACKGROUND: Although tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown. METHODS: Data were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association. RESULTS: The association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (ß=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food. CONCLUSIONS: The association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.

Clinical and pathologic factors associated with the relapse of fibrous gingival hyperplasia.

BACKGROUND: The association between clinicopathologic characteristics and the relapse of fibrous gingival hyperplasia is unknown. METHODS: The records of 211 consecutive patients with a clinicopathologic diagnosis of fibrous gingival hyperplasia were retrieved. Patients who experienced relapse after surgical excision of the lesion were considered case patients (n = 30). All control patients were informed that there was no recurrence (n = 181). Logistic regression was used to evaluate the associations among different characteristics and the recurrence. Stratified analyses on sex was applied to identify the different associations. RESULTS: Binary logistic regression showed that patients with ulcer (odds ratio [OR], 3.23; 95% CI, 1.18 to 8.83) or mechanical stimulation (OR, 2.42; 95% CI, 1.03 to 5.68) had a higher risk of experiencing recurrence. Stratified analysis of sex identified significant association in females (ulcer: OR, 4.04; 95% CI, 1.14 to 14.34; mechanical stimulation: OR, 3.30; 95% CI, 1.15 to 9.42). No significant difference was observed in males (ulcer: OR, 2.44; 95% CI, 0.40 to 15.06; mechanical stimulation: OR, 1.62; 95% CI, 0.28 to 9.40). Male patients with larger epulides had fewer recurrence (OR, 0.13; 95% CI, 0.02 to 0.74). There was no significant difference in pathologic calcification between case and control patients (P > .05). CONCLUSIONS: Patients with ulcer and mechanical stimulation may have a high risk of experiencing recurrent epulis. PRACTICAL IMPLICATIONS: More attention should be paid to patients with ulcer and mechanical stimulation. Apart from complete surgical removal, it is important to remove local stimulation to prevent recurrence of these lesions.

Characterization of structurally related peptide impurities using HPLC-QTOF-MS/MS: application to Cbf-14, a novel antimicrobial peptide.

Cbf-14 (RLLRKFFRKLKKSV), a designed antimicrobial peptide derived from the cathelicidin family, is effective against drug-resistant bacteria. Structurally related peptide impurities in peptide medicines probably have side effects or even toxicity, thus impurity profiling research during the entire production process is indispensable. In this study, a simple liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method using a quadrupole time-of-flight (Q-TOF) mass spectrometer was developed for separation, identification, and characterization of structurally related peptide impurities in Cbf-14. A total of one process-related impurity and thirty-two degradation products were identified, and seven of them have been synthesized and confirmed. These impurities have not been declared in custom synthetic peptides. The degradation products were divided into five categories: fifteen Cbf-14 hydrolysates, five Cbf-14 isomers, four acetyl-Cbf-14 isomers, two aldimine derivatives, and six oxidized impurities. Combined with the peptide synthesis and the stress-testing studies, the origins and the formation mechanisms of these impurities were elucidated, which provides a unique insight for the follow-up quality study of Cbf-14 and other peptide products.

Association between tooth loss and hypertension: A systematic review and meta-analysis.

OBJECTIVES: Poor oral health status may increase the risk of cardiovascular disease. However, whether a specific association exists between tooth loss and hypertension is inconclusive. Accordingly, a quantitative systematic review was conducted to investigate the relationship between tooth loss and hypertension. METHODS: Systematic search, data analysis and quality assessment were conducted on relevant literature published in PubMed, Embase, Web of Science and Cochrane Libraries until October 2021. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to evaluate the association between tooth loss and hypertension. Meta-regression and subgroup analyses were performed to identify whether difference was associated with study-level factors. RESULTS: Of the 56 studies selected, 28 studies in 16 different countries involving 1,224,821 individuals were eligible for the systematic review. After adjustment for confounding factors, individuals with tooth loss had a higher risk for hypertension (OR 1.20; 95%CI 1.10-1.30, I2 = 40.02%). With respect to the risk of hypertension on tooth loss, individuals with hypertension still had a higher risk for tooth loss (OR 1.35; 95%CI 1.07-1.62, I2 = 51.10%). Age limitation of the included population is the major source of heterogeneity. However, studies in which the population was limited to the elderly did not report an increase in association between tooth loss and hypertension compared with studies without age limitation. CONCLUSIONS: The results suggest a bidirectional association between tooth loss and hypertension. Future longitudinal prospective studies are required to establish causality between tooth loss and hypertension. CLINICAL SIGNIFICANCE: Subjects with severe tooth loss should be carefully monitored for the manifestation of hypertension. The oral health status of hypertensive patients should also be meticulous maintained to prevent unwarranted tooth loss.

Smart, Biomimetic Periosteum Created from the Cerium(III, IV) Oxide-Mineralized Eggshell Membrane.

The periosteum orchestrates the microenvironment of bone regeneration, including facilitating local neuro-vascularization and regulating immune responses. To mimic the role of natural periosteum for bone repair enhancement, we adopted the principle of biomimetic mineralization to delicately inlay amorphous cerium oxide within eggshell membranes (ESMs) for the first time. Cerium from cerium oxide possesses unique ability to switch its oxidation state from cerium III to cerium IV and vice versa, which provides itself promising potential for biomedical applications. ESMs are mineralized with cerium(III, IV) oxide and examined for their biocompatibility. Apart from serving as physical barriers, periosteum-like cerium(III, IV) oxide-mineralized ESMs are biocompatible and can actively regulate immune responses and facilitate local neuro-vascularization along with early-stage bone regeneration in a murine cranial defect model. During the healing process, cerium-inlayed biomimetic periosteum can boost early osteoclastic differentiation of macrophage lineage cells, which may be the dominant mediator of the local repair microenvironment. The present work provides novel insights into expanding the definition and function of a biomimetic periosteum to boost early-stage bone repair and optimize long-term repair with robust neuro-vascularization. This new treatment strategy which employs multifunctional bone-and-periosteum-mimicking systems creates a highly concerted microenvironment to expedite bone regeneration.

Nerve electrical stimulation treatment of xerostomia / 口腔疾病防治

@#Patients with impaired quality of life associated with xerostomia need long-term treatment, and a nerve stimulator has the advantage of providing natural saliva and long-term management for patients with xerostomia by electrically stimulating the relevant secretory nerves to promote saliva production. A number of clinical trials have preliminarily demonstrated the efficacy of nerve electrical stimulation in the treatment of xerostomia. However, electrical stimulation has not yet become the mainstream treatment for xerostomia. Large prospective randomized controlled clinical trials are still needed to confirm its long-term effectiveness and safety. In addition, the design of nerve stimulators is of great significance for clinical application. The large volume and inconvenient treatment associated with the extra oral nerve stimulator and the first generation intraoral nerve stimulator hinder their clinical application and popularization. The second- and third-generation intraoral nerve stimulator devices are small, convenient to use and have great application prospects. Research on electrical nerve stimulators for xerostomia treatment is mainly concentrated in European and American countries, while there is very little domestic research. It is urgent to master the core technology for the research and development of electrical nerve stimulators. The innovation of miniaturization, efficient power supply, data feedback and packaging will be the key issues of electrical nerve stimulators in the future. In this paper, the treatment and research of electrical nerve stimulation for xerostomia are reviewed to provide a reference for related basic research and the clinical application of electrical stimulators treating xerostomia in China.

Multifunctional Coatings of Titanium Implants Toward Promoting Osseointegration and Preventing Infection: Recent Developments.

Titanium and its alloys are dominant material for orthopedic/dental implants due to their stable chemical properties and good biocompatibility. However, aseptic loosening and peri-implant infection remain problems that may lead to implant removal eventually. The ideal orthopedic implant should possess both osteogenic and antibacterial properties and do proper assistance to in situ inflammatory cells for anti-microbe and tissue repair. Recent advances in surface modification have provided various strategies to procure the harmonious relationship between implant and its microenvironment. In this review, we provide an overview of the latest strategies to endow titanium implants with bio-function and anti-infection properties. We state the methods they use to preparing these efficient surfaces and offer further insight into the interaction between these devices and the local biological environment. Finally, we discuss the unmet needs and current challenges in the development of ideal materials for bone implantation.

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China.

BACKGROUND: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. METHODS: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. RESULT(S): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. CONCLUSION(S): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.

Methylenetetrahydrofolate reductase gene polymorphisms in the risk of polycystic ovary syndrome and ovarian cancer.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) in hormone metabolism pathways might cause metabolic disturbances and contribute to the development of polycystic ovary syndrome (PCOS) and ovarian cancer, but the published studies were inconsistent. The aim of the present study was to evaluate the MTHFR C677T (rs1801133) and A1298C (rs1801131) gene polymorphisms in the risk of PCOS and ovarian cancer by meta-analysis. A comprehensive electronic search was conducted in databases for studies published from 1995 to 2020. The pooled ORs were calculated by Revman 5.2 software. Twenty-nine articles including 45 case-control studies were included. We found that MTHFR C677T polymorphisms were correlated with elevated PCOS risk (TT vs. CT+CC: OR = 1.41, 95%CI = 1.20-1.67; TT+CT vs. CC: OR = 1.54, 95%CI = 1.07-2.22; CT vs. CC+TT: OR = 1.18, 95%CI 1.04-1.33; TT vs. CC: OR = 1.47, 95%CI = 1.03-2.11; T vs. C: OR = 1.25, 95%CI = 1.06-1.47), which were more obvious in Middle Eastern subgroup. MTHFR A1298C polymorphisms were also associated with overall PCOS susceptibility (CC vs. AC+AA: OR = 2.55, 95% CI = 1.61-4.03; CC+AC vs. AA: OR = 1.84, 95%CI = 1.04-3.28; CC vs. AA: OR = 2.66, 95%CI = 1.68-4.22; C vs. A: OR = 1.67, 95%CI = 1.03-2.71), which were mainly reflected in Asian subjects. For ovarian cancer, MTHFR C677T polymorphisms were only related with elevated ovarian cancer risk in Asian population, while no significant association was found for A1298C polymorphisms. This meta-analysis suggested that MTHFR C677T and MTHFR A1298C polymorphisms were correlated with elevated PCOS risk. MTHFR C667T only posed a higher risk for ovarian cancer in Asians instead of other populations, while MTHFR A1298C polymorphisms were not related to ovarian cancer risk. Further studies are needed to validate the conclusion.

Effects of GW1929 on uterus, ovary and bone metabolism function in perimenopause rats.

This study was aimed to investigate the effect of GW1929, a novel peroxisome proliferator-activated receptors gamma (PPARγ) agonist, in perimenopause rats. Female Sprague-Dawley (SD) rats were treated with 4-vinylcyclohexene diepoxide (VCD) to induce perimenopause rat model. Then they were given GW1929 in low, middle and high dosage. Histopathology observation of uterus and ovary tissues was measured by hematoxylin and eosin staining. The levels of serum hormones, oxidative stress related factors, bone formation and bone metabolism associated factors in serum were detected by kits. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was employed to evaluate cell apoptosis. Furthermore, the expression of PPARγ and apoptosis associated proteins were measured by western blotting. The results revealed that there was no thickening of endometrium and no mature follicular development in ovaries of model group rats. GW1929 treatment recovered endometrial function with a tendency of thickening and there were mature follicle in the ovary. In addition, GW1929 increased the expression of PPARγ in both uterus and ovary tissues. The contents of estrogen (E2) were increased, whereas follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were decreased after being intervened with GW1929 in perimenopause rats. Concurrently, GW1929 reduced the levels of oxidative stress in a dose-dependent manner. Following treatment with GW1929, cell apoptosis in uterus and ovary tissues were attenuated, accompanied by a downregulation of Bax expression and an upregulation of Bcl-2 and cleaved caspase-3 expression. Moreover, In the GW1929-treated perimenopause rats, the levels of alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), bone alkaline phosphatase (BALP) and bone mineral density (BMD) were enhanced, while tartrate-resistant acid phosphatase (TRAP) was reduced. Taken together, we conclude that GW1929 could improve uterus, ovary and bone metabolism function in perimenopause rats, which is of great significance for the treatment of perimenopause.

Study of the Relationship Between Chlorhexidine-Grafted Amount and Biological Performances of Micro/Nanoporous Titanium Surfaces.

Biomaterial-associated infection and lack of sufficient osseointegration contribute to a large proportion of implant failures. Therefore, antibacterial and osseointegration-accelerating properties are important in implant surface design. In this study, a micro/nanoporous titanium surface was prepared through alkaline and heat treatments, covalently conjugated with aminosilane. Then, varying amounts of chlorhexidine (CHX) were covalently grafted onto the aminosilane-modified surface via glutaraldehyde to obtain different CHX-grafted surfaces. These as-prepared surfaces were evaluated in terms of their surface chemical composition, surface topography, CHX grafting amount, antibacterial activity, and osteoblast compatibility. The results showed that the CHX grafting amount increased with increasing CHX concentrations, leading to better antibacterial activity. CHX (1 mg/mL) resulted in the best antibacterial surface, which still retained good osteoblast compatibility. Meanwhile, competitive bacterial-cell adhesion analysis demonstrated that this surface has great value for osteoblast adhesion at the implant-bone interface even in the presence of bacteria. This effortless, easily performed, and eco-friendly technique holds huge promise for clinical applications.

[The Association Between the Polymorphisms of miRNA Biogenesis Related Genes(DICER,DROSHA and RAN)and Unexplained Recurrent Spontaneous Abortion in Chinese Women].

OBJECTIVE: To explore the association between polymorphisms of miRNA biogenesis related gene DICER,DROSHA,RAN and unexplained recurrent spontaneous abortion (URSA) in Chinese women. METHODS: We recruited 217 patients with URSA (URSA group) and 390 healthy controls who were fertile women with history of more than one successful pregnancy outcome (control group) from June 2013 to December 2015 in the West China Second University Hospital of Sichuan University. The control group was recruited from regular physical examination and prepregnancy check for women of childbearing age during the same period. A case-control study was performed to analyze polymorphism of miRNA machinery genes,including DICER rs3742330,DROSHA rs10719, RAN rs14035,by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The frequencies of genotypes and alleles of DICER rs3742330,DROSHA rs10719,and RAN rs14035 showed no difference between URSA patients and control group (all P>0.05). DICER rs3742330/DROSHA rs10719 GG/TC+TT combinations were synergistically associated with increased URSA risk [odds ratio (OR)=1.657,95% confidence interval (CI)=1.006-2.731, P=0.047]. Although DICER rs3742330/RAN rs14035 GG / TT+TC combinations was significantly higher in the URSA group than in the control group,there was no statistical significance (OR=1.977,95%CI=0.956-4.087, P=0.066). However,DROSHA10719/RAN14035 TT+TC/TT+TC had no significant correlation with URSA (OR=0.958,95%CI=0.679-1.353, P=0.808). CONCLUSION: Our study demonstrated the relationship between URSA development and combined genotype of DICER rs3742330/DROSHA rs10719 GG/TC+TT.

Research advances of Dicer in regulating reproductive function.

Dicer, an RNAse III endonuclease, is critical for the biogenesis of small noncoding RNAs (microRNAs), including the biogenesis of microRNAs and small interfering RNAs, which transcriptionally and post-transcription ally regulate mRNA expression through binding to target mRNA and leading to subsequent mRNA degradation. Recent studies show that Dicer plays important roles in cell proliferation, differentiation and apoptosis. It has been attracted more and more attention in the reproductive field. In the male reproduction field, mouse model shows that Dicer is critical for the development of spermatogenic cell, sperm maturation, sperm motility and morphology. On the other hand, Dicer is broadly involved in not only follicular development, ovulation, luteinization, sex hormone synthesis, but also regulating the functions of the fallopian tube, endometrial receptivity in female reproduction. Since sperm and egg are the only two types of gametes for producing offspring, Dicer dysregulation may be the underlying cause of compromised embryo development through affecting the quantity or quality of sperm and eggs. Therefore, understanding the function of Dicer in reproduction of female and male is of great significance to study the pathogenetic mechanism related to dysfunctional reproduction, such as azoospermia and recurrent spontaneous abortion. We review the pivotal roles of Dicer in the male and female reproduction field in order to understand the relationship between Dicer and related disease.

[Association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia].

OBJECTIVE: To assess the association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia. METHODS: For 330 patients with primary azoospermia and 282 fertile male controls, single nucleotide polymorphisms (SNPs) of DICER rs3742330 and DROSHA rs10719 were determined with a restriction fragment length polymorphism (RFLP) method. RESULTS: For the SNP rs3742330, the frequency of A allele was higher among azoospermia patients compared with the controls (72.0% vs.64.4%, P=0.004), and so was the frequency of AA genotype (53.0% vs. 41.8%, P=0.027, OR=1.829, 95%CI: 1.071-3.124). On the other hand, the allelic and genotypic frequencies of rs10719 did not differ between the two groups (all P > 0.05). CONCLUSION: Polymorphisms of rs3742330 of the DICER gene, particularly the AA genotype, may be associated with azoospermia.

The impact of drying on structure of sedimentary organic matter in wetlands: Probing with native and amended polycyclic aromatic hydrocarbons.

Wetland sediments undergo dry-wet cycles that may change their structural properties and affect geochemical behavior of associated organic compounds. In this study, we examined the effect of drying on particle size distributions and the rapid (24h) sorption reactions of polycyclic aromatic hydrocarbons (PAHs) with salt marsh sediments in Nueces Delta, South Texas. Drying reduced the fraction of fine particles in organically richer sediments, indicating structural rearrangement of organic matter and mineral aggregates. Among the 16 EPA priority PAHs examined, dried sediment preferentially released 1.0-7.5% of phenanthrene, fluoranthene and pyrene to added seawater (solid: water mass ratio of 1/100) - significantly greater than release from sediments maintained in the wet state. On the other hand, drying also increased the affinity of sedimentary organic matter (SOM) for experimentally amended (deuterated) phenanthrene relative to continually wet sediments. Further, deuterated phenanthrene was even more effectively retained when it was added to wet sediment that was subsequently dried and rewetted. These apparently contradictory results can be reconciled and explained by SOM having a heterogeneous distribution of hydrophobic and hydrophilic zones - e.g., a zonal model. We propose that drying changed the orientation of amphiphilic SOM, exposing hydrophobic zones and promoting the release of some of their native PAHs to water. Freshly amended PAHs were only able to penetrate into the surface hydrophobic zone and/or deeper but rapidly accessible ("kinetic") zone in wet sediments due to the brief adsorption contact time. Subsequent drying presumably then induced structural changes in SOM that isolated these amended PAHs in sites inaccessible to water exchange in the next rewetting. These results provide insights into structural changes of SOM upon drying, and help predict the fate of compounds such as organic contaminants during drought/flood oscillations.