Enantioselective Synthesis of Axially Chiral Sulfone-Containing Styrenes Based on Ion-Exchange Strategy.

A novel ion exchange strategy has been developed to enable the asymmetric construction of axially chiral sulfone-containing styrenes. This approach provides a practical synthesis pathway for various axially chiral sulfone-containing styrenes with good yields, exceptional enantioselectivities, and nearly complete E/Z selectivities. Additionally, the reaction mechanism is elucidated in detail through density functional theory (DFT) calculations.

Cooperative Cu/azodiformate system-catalyzed allylic C-H amination of unactivated internal alkenes directed by aminoquinoline.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

Stereoselective Sulfa-Michael/Aldol Reaction Promoted by an Axially Chiral Styrene-Based Organocatalyst.

Herein, we describe a stereoselective sulfa-Michael/aldol cyclization reaction promoted by a rationally designed novel axially chiral styrene-based organocatalyst. A variety of highly substituted tetrahydrothiophenes featuring an alkyne-substituted quaternary stereogenic center are obtained in good yields, excellent stereoselectivities, and exclusive trans selectivities. This process tolerates a broad range of alkynyl-substituted acrylamides under mind conditions. The utility of this approach is highlighted in its excellent asymmetric introduction, scalability, and attractive product diversification.

Strain Identification and Drug Resistance Analysis of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Nontuberculous Mycobacterial Lung Disease.

Objective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM). Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations. Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P<0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P<0.001, kappa=0.781). Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.

Prevalence and risk factors for subjective cognitive decline and the correlation with objective cognition among community-dwelling older adults in China: Results from the Hubei memory and aging cohort study.

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.

Molecular mechanism of fatty acid activation of FFAR1.

FFAR1 is a G-protein-coupled receptor (GPCR) that responds to circulating free fatty acids to enhance glucose-stimulated insulin secretion and release of incretin hormones. Due to the glucose-lowering effect of FFAR1 activation, potent agonists for this receptor have been developed for the treatment of diabetes. Previous structural and biochemical studies of FFAR1 showed multiple sites of ligand binding to the inactive state but left the mechanism of fatty acid interaction and receptor activation unknown. We used cryo-electron microscopy to elucidate structures of activated FFAR1 bound to a Gq mimetic, which were induced either by the endogenous FFA ligand docosahexaenoic acid or γ-linolenic acid and the agonist drug TAK-875. Our data identify the orthosteric pocket for fatty acids and show how both endogenous hormones and synthetic agonists induce changes in helical packing along the outside of the receptor that propagate to exposure of the G-protein-coupling site. These structures show how FFAR1 functions without the highly conserved "DRY" and "NPXXY" motifs of class A GPCRs and also illustrate how the orthosteric site of a receptor can be bypassed by membrane-embedded drugs to confer full activation of G protein signaling.

Relationship between lipids and sleep apnea: Mendelian randomization analysis.

BACKGROUND: Lipids increase the risk of sleep apnea; however, the causality between them is still inconclusive. AIM: To explore the causal relationship between serum lipids and sleep apnea using two-sample Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphism (SNP) data related to serum lipids were obtained from the Global Lipids Genetics Consortium study, which included 188578 individuals of European ancestry. Additionally, sleep apnea-related SNP data were collected from the United Kingdom Biobank study, which comprised 463005 individuals of European ancestry. Two-sample MR analysis was performed to assess the causality between serum lipids and sleep apnea based on the above public data. RESULTS: Genetically predicted low-density lipoprotein (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.99 to 1.00; P = 0.58), high-density lipoprotein (OR = 0.99, 95%CI = 0.99 to 1.00; P = 0.91), triglyceride (OR = 1.00, 95%CI = 0.99 to 1.00; P = 0.92), and total cholesterol (OR = 0.99, 95%CI = 0.99 to 1.00; P = 0.33) were causally unrelated to sleep apnea. CONCLUSION: Our MR analysis suggests that genetically predicted serum lipids are not risk factors of sleep apnea.

The Relevance of Host Gut Microbiome Signature Alterations on de novo Fatty Acids Synthesis in Patients with Multi-Drug Resistant Tuberculosis.

Background: Tuberculosis (TB) is still the single pathogen infectious disease with the largest number of deaths worldwide. The relationship that intestinal microbiota disorder and de novo fatty acid synthesis metabolism have with disease progression in multi-drug resistant TB (MDR-TB) has not yet been fully studied. Objective: To investigate the effects of long periods of MDR-TB, pre-extensively drug-resistant TB (pre-XDR-TB), or rifampicin-resistant TB (RR-TB) on gut microbiome dysbiosis and advanced disease. Methods: The sample was chosen between March 2019 and September 2019 in Wenzhou Central Hospital and comprised 11 patients with pre-XDR-TB, 23 patients with RR-TB, and 28 patients with MDR-TB. Healthy individuals were chosen as the control group (CK group). An overnight fast blood sample was drawn via venipuncture into tubes without anticoagulant. For analysis, 300 mg of faeces from patients from the same group was mixed and analysed using DNA extraction, NGS sequencing, and bioinformatics. A QIAamp Fecal DNA Mini Kit was used to isolate the DNA. The extracted DNA was stored at -20°C. Results: Advanced TB was concurrent with an elevated level of the proportions of acetyl-CoA carboxylase (ACC1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthase (FASN) to GAPDH in de novo fatty acids synthesis, and Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus were increased significantly in RR-TB patients compared to healthy individuals, whereas their abundance in the pre-XDR-TB and MDR-TB groups showed little change in comparison with the control group. Proteobacteria levels were greatly increased in the RR-TB and MDR-TB patient groups but not in the patients with pre-XDR-TB or the healthy subjects. The pre-XDR-TB group exhibited alterations of the intestinal microbiome: coliform flora showed the highest abundance of Verrucomicrobiales, Enterobacteriales, Bifidobacteriales and Lactobacillales. De novo fatty acids synthesis was enhanced in patients and was associated with the gut microbiome dysbiosis induced by the antimicrobials, with Bacteroidetes, Bacteroidales, and Bacteroidaceae displaying the most important correlations on a phylum, order, and family level, respectively. Conclusion: The progression to advanced TB was observed to be a result of the interaction between multiple interrelated pathways, with gut-lung crosstalk potentially playing a role in patients with drug-resistant TB.

Plasma Phage Load is Positively Related to the Immune Checkpoints in Patients Living with Human Immunodeficiency Virus.

BACKGROUND: Microbial Translocation (MT) and altered gut microbiota are involved in immune activation and inflammation, whereas immune checkpoint proteins play an important role in maintaining immune self-tolerance and preventing excessive immune activation. OBJECTIVE: This study aims to investigate the relationship between plasma phage load and immune homeostasis in people living with HIV(PLWH). METHODS: We recruited 15 antiretroviral therapy (ART)-naive patients, 23 ART-treated (AT) patients, and 34 Healthy Participants (HP) to explore the relationship between the plasma phage load and immune checkpoint proteins. The Deoxyribonucleic Acid (DNA) load of the lambda (λ) phage was detected using fluorescence quantitative Polymerase Chain Reaction (PCR). The Immune Checkpoints (ICPs) were detected using multiplex immunoassay. RESULTS: Our study demonstrated that the plasma phage load was increased in people living with HIV (PLWH) (P<0.05), but not in the ART-naive and AT groups (P>0.05). Plasma ICPs, including cluster of differentiation 27 (CD27), soluble glucocorticoid-induced Tumor Necrosis Factor (TNF) receptor (sGITR), soluble cluster of differentiation 80 (sCD80), sCD86, soluble glucocorticoidinduced TNF receptor-related ligand (sGITRL), soluble induced T-cell Costimulatory (sICOS), sCD40, soluble toll-like receptor 2 (sTLR2), and sCD28, were markedly decreased among the ARTnaive group (P<0.05) but not in the AT and HP groups (P>0.05). The plasma phage load was positively correlated with ICP and C-reactive protein (CRP) levels in PLWH (P<0.05). CONCLUSION: Our study indicated that the plasma phage load in PLWH was positively related to the expression of ICPs and inflammation, which may be used as a promising marker for the immune level of PLWH.

Bioinspired Palladium-Catalyzed Intramolecular C(sp3 )-H Activation for the Collective Synthesis of Proline Natural Products.

Bioinspired palladium-catalyzed intramolecular cyclization of amino acid derivatives containing a vinyl iodide moiety by C-H activation enabled rapid access to a wide range of functionalized proline derivatives with an exocyclic olefin. To demonstrate the practicality of this methodology, the functionalized prolines were used as intermediates for the synthesis of several natural products: lucentamycin A, oxotomaymycin, oxoprothracarcin, and barmumycin.

Molecular mechanism of the wake-promoting agent TAK-925.

The OX2 orexin receptor (OX2R) is a highly expressed G protein-coupled receptor (GPCR) in the brain that regulates wakefulness and circadian rhythms in humans. Antagonism of OX2R is a proven therapeutic strategy for insomnia drugs, and agonism of OX2R is a potentially powerful approach for narcolepsy type 1, which is characterized by the death of orexinergic neurons. Until recently, agonism of OX2R had been considered 'undruggable.' We harness cryo-electron microscopy of OX2R-G protein complexes to determine how the first clinically tested OX2R agonist TAK-925 can activate OX2R in a highly selective manner. Two structures of TAK-925-bound OX2R with either a Gq mimetic or Gi reveal that TAK-925 binds at the same site occupied by antagonists, yet interacts with the transmembrane helices to trigger activating microswitches. Our structural and mutagenesis data show that TAK-925's selectivity is mediated by subtle differences between OX1 and OX2 receptor subtypes at the orthosteric pocket. Finally, differences in the polarity of interactions at the G protein binding interfaces help to rationalize OX2R's coupling selectivity for Gq signaling. The mechanisms of TAK-925's binding, activation, and selectivity presented herein will aid in understanding the efficacy of small molecule OX2R agonists for narcolepsy and other circadian disorders.

Aggressive Angiomyxoma in the Scrotum: A Case Series and Literature Review.

Purpose: Aggressive angiomyxoma (AAM) was identified as a distinct clinicopathological entity in 1983. Since then, a few cases of its occurrence in the scrotum have been reported. This case series was performed to increase clinicians' understanding of the clinical features and treatment of AAM in the scrotum. Methods: We evaluated the clinical presentations, treatments, and follow-up of two patients with AAM in the scrotum in our hospital and 34 cases reported in the literature. Results: Among the 36 patients, the average age was 48.3 ± 20.6 years old (range from 1 to 81); the average maximum diameter of the tumor was 8.36 cm (1.6-25 cm); the site of one (2.78%) patient was located in the epididymis, two (5.56%) in the testes, five (13.89%) in the spermatic cord, and 28 (77.77%) in the scrotum. The clinical symptoms were generally non-specific and 20 patients inadvertently discovered their slow-growing painless masses. The treatments for all these patients were surgical excision once the tumor had been found and one case underwent excision followed by radiotherapy. The median follow-up time for the remaining 32 cases was 24.5 months (1 to 84 months). Recurrence occurred in three cases (9.09%) at the primary sites and no cases of distant metastasis. Conclusion: AAM of the scrotum can occur in middle-aged and elderly men. The clinical manifestation generally involves a long history of asymptomatic masses or swelling in the scrotum. Ultrasound is the most commonly used diagnostic technique but magnetic resonance imaging may be more effective. The mainly treatment is surgical excision and postoperative histopathological examination is still the gold standard for its diagnosis. Although it is locally aggressive, metastasis is extremely rare in males.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

The functional role of inherited CDKN2A variants in childhood acute lymphoblastic leukemia.

OBJECTIVE: Genetic alterations in CDKN2A tumor suppressor gene on chromosome 9p21 confer a predisposition to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies have identified missense variants in CDKN2A associated with the development of ALL. This study systematically evaluated the effects of CDKN2A coding variants on ALL risk. METHODS: We genotyped the CDKN2A coding region in 308 childhood ALL cases enrolled in CCCG-ALL-2015 clinical trials by Sanger Sequencing. Cell growth assay, cell cycle assay, MTT-based cell toxicity assay, and western blot were performed to assess the CDKN2A coding variants on ALL predisposition. RESULTS: We identified 10 novel exonic germline variants, including 6 missense mutations (p.A21V, p.G45A and p.V115L of p16INK4A; p.T31R, p.R90G, and p.R129L of p14ARF) and 1 nonsense mutation and 1 heterozygous termination codon mutation in exon 2 (p16INK4A p.S129X). Functional studies indicate that five novel variants resulted in reduced tumor suppressor activity of p16INK4A, and increased the susceptibility to the leukemic transformation of hematopoietic progenitor cells. Compared to other variants, p.H142R contributes higher sensitivity to CDK4/6 inhibitors. CONCLUSION: These findings provide direct insight into the influence of inherited genetic variants at the CDKN2A coding region on the development of ALL and the precise clinical application of CDK4/6 inhibitors.

Population-attributable fractions of risk factors for all-cause dementia in China rural and urban areas: a cross-sectional study.

BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

Effects of Micellization Behavior on the Interfacial Adsorption in Binary Anionic/Nonionic Surfactant Systems: A Molecular Simulation Study.

A surfactant interfacial adsorption process is highly associated with its micellization behaviors in the water phase, which is of great fundamental and practical significance in enhanced oil recovery. In this paper, the typical anionic surfactant 1-dodecanesulfonic acid sodium (DAS) and nonionic surfactants octylphenol polyoxyethylene ether-n (OP-n, n = 1, 5, and 10) are introduced to investigate their micellization behavior and interfacial adsorption process via molecular dynamics simulation. Number density profiles reveal that the additional OP5 molecules in the water phase generate the mixed micelle with DAS molecules and greatly promote its interfacial adsorption. Interaction energy calculation is employed to confirm the interaction of anionic/nonionic surfactants in the mixed micelle. Then, the radial distribution function, solvent-accessible surface area, and solvation free energy are calculated to further explore and verify the adsorption mechanism of the mixed micelle. It is found that the nonionic surfactant obviously decreases the hydrophilicity of the mixed micelle in the water phase, which should be responsible for its intensive tendency of the interfacial adsorption.

Urban-Rural Disparities in the Association Between Body Mass Index and Cognitive Impairment in Older Adults: A Cross-Sectional Study in Central China.

BACKGROUND: Some studies have demonstrated an association between low and high body mass index (BMI) and an increased risk of dementia. However, only a few of these studies were performed in rural areas. OBJECTIVE: This cross-sectional study investigated the associations between BMI and cognitive impairment among community-dwelling older adults from rural and urban areas. METHODS: 8,221 older persons enrolled in the Hubei Memory & Ageing Cohort Study (HMACS) were recruited. Sociodemographic and lifestyle data, comorbidities, physical measurements, and clinical diagnoses of cognitive impairment were analyzed. Logistic regression was performed to assess the associations of BMI categories with cognitive impairment. A series of sensitivity analyses were conducted to test whether reverse causality could influence our results. RESULTS: Being underweight in the rural-dwelling participants increased the risk of cognitive impairment. Being overweight was a protective factor in rural-dwelling participants aged 65-69 years and 75-79 years, whereas being underweight was significantly associated with cognitive impairment (OR, 1.37; 95% CI: 1.03-1.83; p < 0.05). Sensitivity analyses support that underweight had an additive effect on the odds of cognitive impairment and was related to risk of dementia. Interaction test revealed that the differences between urban/rural in the relationship between BMI and cognitive impairment are statistically significant. CONCLUSION: Associations between BMI and cognitive impairment differ among urban/rural groups. Older people with low BMI living in rural China are at a higher risk for dementia than those living in urban areas.

Safety and efficiency of sewage sludge and garden waste compost as a soil amendment based on the field application in woodland.

Sewage sludge (SS) and garden waste (GW) compost can be used as soil amendments to improve the soil environment. Studies done till date have been focused on the changes of harmful substances during sludge composting, but the safety and efficacy of SS and GW composting on woodland soil environment are still unclear. In the study, a field experiment was performed using to investigate the safety and efficacy of SS and GW compost as a soil amendment on woodland soil. Soil nutrients (such as nitrogen, phosphorus and potassium), organic matter and electrical conductivity were significantly increased after the addition of the SS and GW compost, while there were no significant changes in soil heavy metals content and soil enzyme activities. From these soil properties, it was found that SS and GW compost was safe and efficacious in improving the soil environment. The application of SS and GW compost had no significant effect on microbial diversity. Co-occurrence network analysis revealed that SS and GW compost efficaciously enhanced the interaction between bacterial communities, which proved that it was safe and efficacious. Furthermore, SS and GW compost enhanced ABC transporters and carbohydrate metabolism of bacterial community, while reduced the pathotroph action (such as the plant pathogen) and wood saprotrophs. Overall, these results proved the safety and efficacy of SS and GW compost as soil amendments after being added to the soil. This study contributes to the use of harmless treatments and reutilization processes of SS and GW.

Mechanistic Investigation of Dimethylmercury Formation Mediated by a Sulfide Mineral Surface.

Mercury (Hg) pollution is a global environmental problem. The abiotic formation of dimethylmercury (DMeHg) from monomethylmercury (MMeHg) may account for a large portion of DMeHg in oceans. Previous experimental work has shown that abiotic formation of DMeHg from MMeHg can be facilitated by reduced sulfur groups on sulfide mineral surfaces. In that work, a mechanism was proposed in which neighboring MMeHg moieties bound to sulfide sites on a mineral surface react through an SN2-type mechanism to form DMeHg and incorporate the remaining Hg atoms into the mineral surface. Here, we perform density functional theory calculations to explore the mechanisms of DMeHg formation on the 110 surface of a CdS(s) (hawleyite) nanoparticle. We show that coordination of MMeHg substituents to adjacent reduced sulfur groups protruding from the surface indeed facilitates DMeHg formation and that the reaction proceeds through direct transmethylation from one MMeHg substituent to another. Coordination of Hg by multiple S atoms provides a transition-state stabilization and activates a C-Hg bond for methyl transfer. In addition, solvation effects play an important role in the surface reconstruction of the nanoparticle and in decreasing the energetic barrier for DMeHg formation relative to the corresponding reaction in vacuo.