Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.

Heroin dependence (HD) is a complex disease with a substantial genetic contribution and is associated with traits of impulsivity and specific personality traits. The neurotrophic factor nerve growth factor (NGF) may mediate the reward processes in HD. This study aims to investigate whether NGF gene polymorphisms are associated with the co-occurrence of HD and impulsivity/specific personality traits in HD patients. To minimize the potential confounding effects of population stratification, we selected a homogeneous Han Chinese population and recruited 1364 participants (831 HD patients and 533 healthy controls). In addition, 163 female HD patients completed the Chinese version of the Barratt Impulsiveness Scale Version 11 (BIS-11), and 440 HD patients completed the Chinese version of the Tridimensional Personality Questionnaire (TPQ) for subsequent analysis. We identified three polymorphisms with altered allele and genotype frequency in HD patients versus controls (p = 0.035 for rs2254527; p = 0.005 for rs6678788; p = 0.006 for rs7523654), especially in the female subgroup. Four associations identified via haplotype analysis were significant in the female subgroup (p = 0.003 for T-T-A haplotype and p = 0.002 for C-C-A haplotype in block 1; p = 0.011 for T-T haplotype and p = 0.009 for C-T haplotypes in block 2), but not in the male subgroup. Male HD patients had higher novelty-seeking (NS) scores, and female HD patients had higher harm avoidance (HA) scores. However, there was no significant association between the selected NGF polymorphisms and BIS or TPQ scores in HD patients. NGF variants may contribute to the risk of HD development in females but do not mediate the relationship between impulsivity and specific personality traits in the female population.

Neurogenetic underpinnings of nicotine use severity: Integrating the brain transcriptomes and GWAS variants via network approaches.

Our study focused on human brain transcriptomes and the genetic risks of cigarettes per day (CPD) to investigate the neurogenetic mechanisms of individual variation in nicotine use severity. We constructed whole-brain and intramodular region-specific coexpression networks using BrainSpan's transcriptomes, and the genomewide association studies identified risk variants of CPD, confirmed the associations between CPD and each gene set in the region-specific subnetworks using an independent dataset, and conducted bioinformatic analyses. Eight brain-region-specific coexpression subnetworks were identified in association with CPD: amygdala, hippocampus, medial prefrontal cortex (MPFC), orbitofrontal cortex (OPFC), dorsolateral prefrontal cortex, striatum, mediodorsal nucleus of the thalamus (MDTHAL), and primary motor cortex (M1C). Each gene set in the eight subnetworks was associated with CPD. We also identified three hub proteins encoded by GRIN2A in the amygdala, PMCA2 in the hippocampus, MPFC, OPFC, striatum, and MDTHAL, and SV2B in M1C. Intriguingly, the pancreatic secretion pathway appeared in all the significant protein interaction subnetworks, suggesting pleiotropic effects between cigarette smoking and pancreatic diseases. The three hub proteins and genes are implicated in stress response, drug memory, calcium homeostasis, and inhibitory control. These findings provide novel evidence of the neurogenetic underpinnings of smoking severity.

Fabrication of CoSe2/CoP with rich selenium- and phosphorus-vacancies and heterogeneous interfaces for asymmetric supercapacitors.

CoSe2/CoP with rich Se- and P-vacancies and heterogeneous interfaces (v-CoSe2/CoP) is grown on the surface of nickel foam via a two-step strategy: electrodeposition and NaBH4 reduction, which can be used as the cathode material in asymmetric supercapacitors. The SEM characterization reveals the honeycomb-like structure of the v-CoSe2/CoP, and the results of EPR, XPS and HRTEM reveal the existence of anionic vacancies and heterogeneous interfaces in the v-CoSe2/CoP. The as-fabricated v-CoSe2/CoP exhibits high specific capacitance (3206 mF cm-2 at 1.0 mA cm-2) and cyclic stability (91 % capacitance retention after 2000 cycles). An asymmetric supercapacitor is assembled by using the v-CoSe2/CoP and activated carbon (AC) as cathode and anode materials, respectively, which displays a high energy density of 40.6 Wh kg-1 at the power density of 211.5 W kg-1. The outstanding electrochemical performances of the v-CoSe2/CoP might be ascribed to the synergistic effects of Se- and P-vacancies and the heterogeneous interfaces in the v-CoSe2/CoP.

Highly Reliable Chiral Discrimination of Tryptophan Enantiomers through Two Different Modes: Electrochemistry and Temperature.

Reliable chiral discrimination of enantiomers with simple devices is of great importance for chiral analysis. Here, a chiral sensing platform is developed for chiral discrimination through two different modes: electrochemistry and temperature. Au nanoparticles (AuNPs) are grown in situ on the nanosheets of MXene by utilizing the strong metal reduction ability of MXene, which can be further used for the anchoring of N-acetyl-l-cysteine (NALC), a commonly used chiral source, through Au-S bonds. Owing to the excellent electrical conductivity and photothermal conversion efficiency of MXene, the resultant MXene-AuNPs-NALC is applied in the construction of a chiral sensing platform for the discrimination of tryptophan (Trp) enantiomers through two different modes: electrochemistry and temperature. Compared with conventional single-mode chiral sensors, the proposed chiral sensing platform can integrate two different indicators (currents and temperature) into one chiral sensor, greatly improving the reliability of chiral discrimination.

Differences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder.

Background: The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD. Method: We recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits. Result: Compared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05). Conclusion: Our findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.

A chiral sensing platform based on a multi-substituted ferrocene-cuprous ion complex for the discrimination of electroactive amino acid isomers.

An electrochemical chiral sensing platform based on a multi-substituted ferrocene-cuprous ion (Cu+) complex is constructed for the discrimination of electroactive amino acid (AA) isomers. Due to the opposite configurations of the AA isomers, the developed multi-substituted ferrocene-Cu+ can preferably combine with a right-handed AA (D-AA) isomer to form the ternary complex of multi-substituted ferrocene-Cu+-D-AA through π-π interactions, resulting in higher peak currents of D-AA. Therefore, the isomers of electroactive AA can be successfully discriminated. Among the tested electroactive AA isomers, the chiral sensing platform exhibits higher discrimination capability toward the isomers of tryptophan (Trp) than that of tyrosine (Tyr) and cysteine (Cys), which might be ascribed to the stronger π-π interactions between the benzene ring of the multi-substituted ferrocene and the indole ring of the Trp isomers.

An electrochemical chiral sensor based on competitive host-guest interaction for the discrimination of electroinactive amino acids.

A novel electrochemical chiral sensor has been designed based on the principle of competitive host-guest interaction and utilized for the discrimination of electroinactive proline (Pro) isomers. Electroactive methylene blue (MB) was used as the signal probe, which was combined with multi-walled carbon nanotubes (MWCNTs)-decorated ß-cyclodextrin (ß-CD), via host-guest interaction, where the oxidation peak currents of MB decreased after isomers of Pro were combined with the MWCNTs-ß-CD via a competitive host-guest interaction. Due to the steric configuration of L-Pro matching the cavity of ß-CD, more L-Pro than D-Pro was combined with MWCNTs-ß-CD, resulting in a more pronounced decrease of MB peak currents. Therefore, the isomers of Pro could be discriminated. Besides Pro, the isomers of electroinactive histidine (His) could also be discriminated with the chiral sensor. In addition, the contents of L-Pro in non-racemic mixtures could be detected with the developed chiral sensor.

Diagnostic Reliability and Validity of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) Chinese Version.

The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a polydiagnostic instrument for substance use and psychiatric disorders. We translated the SSADDA English version into Chinese (SSADDA-Chinese) and report here our examination of the diagnostic reliability and validity of DSM-IV substance dependence (SD) diagnoses in a Mandarin-speaking sample in Taiwan. We recruited 125 subjects who underwent an assessment of lifetime SD diagnoses using both the SSADDA-Chinese and the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-Chinese). Thirty-one subjects were retested with the SSADDA-Chinese. Cohen's κ statistic, which measures chance-corrected agreement, was used to measure the test-retest reliability and concurrent validity of the individual SD diagnoses. There was a high degree of concordance between SD diagnoses made using the SSADDA-Chinese and the SCID-Chinese, including those for dependence on alcohol (κ = 0.83), ketamine (κ = 0.97), methamphetamine (κ = 0.93), and opioids (κ = 0.95). The test-retest reliability of dependence diagnoses for ketamine (κ = 0.95), methamphetamine (κ = 0.80), and opioids (κ = 1.00) obtained using the SSADDA-Chinese was excellent, while that for alcohol dependence (κ = 0.63) and nicotine dependence (κ = 0.65) was good. We conclude that the SSADDA-Chinese is a reliable and valid instrument for the diagnosis of major SD traits in Mandarin-speaking populations.

Reliability and validity of DSM-IV and DSM-5 methamphetamine use disorder diagnoses using the Chinese Version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

BACKGROUND: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) was developed to assess substance-use disorders and other psychiatric traits. We translated the SSADDA into Chinese and evaluated its inter-rater reliability and concurrent validity in diagnosing DSM-IV methamphetamine (MA) dependence and DSM-5 MA-use disorder (MUD). METHODS: The sample comprised 231 participants who were interviewed using the Chinese SSADDA and the Mini-International Neuropsychiatric Interview (Chinese MINI) for concurrent validation. Of the 231 participants, 191 were interviewed by two different interviewers two weeks apart. We evaluated the inter-rater reliability and concurrent validity of the diagnoses using percent agreement and Cohen's kappa coefficient (κ). Cohen's linear weighted kappa was used to assess the reliability of DSM-5 MUD severity. RESULTS: It showed good inter-rater reliability and no significant differences among the DSM-5 MUD (κ = 0.71), DSM-IV MA abuse or dependence (κ = 0.72), and the DSM-IV diagnoses of MA dependence (κ = 0.66) and abuse (κ = 0.68) tested separately. The weighted kappa was 0.67 across the three DSM-5 MUD severity levels. The reliability of each individual diagnostic criterion for DSM-5 MUD ranged from fair to excellent (κ = 0.41-0.80), except for "repeated attempts to quit/control use" (κ = 0.38). The concurrent validity based on MINI-derived diagnoses ranged from good to excellent (κ = 0.65-0.78). CONCLUSIONS: This study shows that the Chinese version of SSADDA has good reliability and validity among Chinese MA users.

Electrochemiluminescent chiral discrimination with chiral Ag2S quantum dots/few-layer carbon nitride nanosheets.

Well-dispersed chiral Ag2S quantum dots (Ag2S QDs) were facilely synthesized by using N-acetyl-L-cysteine (NALC) as the chiral ligand and loaded onto nanosheets of two-dimensional (2D) few-layer carbon nitride (C3N4). The resultant nanocomposite (Ag2S QDs/few-layer C3N4) shows enhanced electrochemiluminescence (ECL) while maintaining the chirality of Ag2S QDs, which can be used for the chiral discrimination of the enantiomers of tyrosine (Tyr). Due to the higher affinity of chiral Ag2S QDs toward L-Tyr than toward its enantiomer, the ECL intensity of Ag2S QDs/few-layer C3N4 is significantly decreased after its incubation with L-Tyr, and thus the Tyr enantiomers can be discriminated. The developed ECL chiral sensor exhibits high stability and reproducibility. The universality of the ECL chiral sensor for the discrimination of other chiral amino acids is also studied, and the results indicate that it can work only in the case of chiral aromatic amino acids.

GABAergic polygenic risk for cocaine use disorder is negatively correlated with precuneus activity during cognitive control in African American individuals.

Impaired cognitive control has been implicated in cocaine use disorder (CUD). GABAergic treatments have been proposed for CUD. Here we examined relationships between GABAergic genes and neural correlates of cognitive control in CUD. We analyzed two independent African American cohorts: one of >3000 genomewide-genotyped subjects with substance dependence and another of 40 CUD and 22 healthy control (HC) subjects who were exome-array genotyped and completed an fMRI Stroop task. We used five association thresholds to select variants of GABAergic genes in the reference cohort, yielding five polygenic risk scores (i.e., CUD-GABA-PRSs) for the fMRI cohort. At p < 0.005, the CUD-GABA-PRSs, which aggregated relative risks of CUD from 89 variants harboring in 16 genes, differed between CUD and HC individuals in the fMRI sample (p = 0.013). This CUD-GABA-PRS correlated inversely with Stroop-related activity in the left precuneus in CUD (r = -80.58, pFWE < 0.05) but not HC participants. Post-hoc seed-based connectivity analysis of the left precuneus identified reduced functional connectivity to the posterior cingulate cortex (PCC) in CUD compared to HC subjects (p = 0.0062) and the degree of connectivity correlated with CUD-GABA-PRSs in CUD individuals (r = 0.287, p = 0.036). Our findings suggest that the GABAergic genetic risk of CUD in African Americans relates to precuneus/PCC functional connectivity during cognitive control. Identification of these GABAergic processes may be relevant targets in CUD treatment. The novel identification of 16 GABAergic genes may be investigated further to inform treatment development efforts for this condition that currently has no medication with a formal indication for its treatment.

Gut dysbiosis associated with the rats' responses in methamphetamine-induced conditioned place preference.

Methamphetamine (MA) is a potent stimulant and notoriously addictive. Individuals respond to MA effects differently and thus have a varying susceptible risk of developing MA use disorder. Cumulative evidence has indicated that gut dysbiosis contributes to behavioral response to drug effects. However, the role of gut microbiota in the susceptible risk of developing MA use disorder has remained elusive. Using an MA-induced conditioned place preference (CPP) rat model, we administrated the same dose of MA to rats, which then showed distinct preferences in drug-related place, indicating their different responses to MA. From all of the MA-exposed rats, the eight with the highest CPP scores were labeled as group high CPP (H-CPP), and the eight with the lowest were labeled as group low CPP (L-CPP). By 16S ribosomal RNA (rRNA) sequencing, we found that the gut microbiota compositions differed between H-CPP and L-CPP. Specifically, Akkermansia was significantly higher in H-CPP and positively correlated with the CPP scores. Notably, H-CPP and L-CPP differed in the gut microbiota composition prior to the CPP training; Ruminococcus was the dominant phylotype in H-CPP at baseline. More importantly, rats pretreated by antibiotics showed a significantly stronger MA-induced CPP than did the controls. Our study demonstrates that the gut dysbiosis was associated with the MA-induced CPP, indicating that the gut microbiota might be important modulators for MA-induced behavior and vulnerability to MA use disorder.

Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children.

The goal of the current study was to evaluate the impact of Tubulin Polymerization Promoting Protein (TPPP) methylation on structural and fractional anisotropy (FA) corpus callosum (CC) measures. TPPP is involved in the development of white matter tracts in the brain and was implicated in stress-related psychiatric disorders in an unbiased whole epigenome methylation study. The cohort included 63 participants (11.73 y/o ±1.91) from a larger study investigating risk and resilience in maltreated children. Voxel-based morphometry (VBM) was used to process the structural data, fractional anisotropy (FA) was determined using an atlas-based approach, and DNA specimens were derived from saliva in two batches using the 450 K (N = 39) and 850 K (N = 24) Illumina arrays, with the data from each batch analyzed separately. After controlling for multiple comparisons and relevant covariates (e.g., demographics, brain volume, cell composition, 3 PCs), 850 K derived TPPP methylation values, in interaction with a dimensional measure of children's trauma experiences, predicted left and right CC body volumes and genu, body and splenium FA (p < .007, all comparisons). The findings in the splenium replicated in subjects with the 450 K data. The results extend prior investigations and suggest a role for TPPP in brain changes associated with stress-related psychiatric disorders.

Oxometalate and phosphine ligand co-protected silver nanoclusters: Ag28(dppb)6(MO4)4 and Ag32(dppb)12(MO4)4(NO3)4.

Thiols, alkynyls and phosphines are the most widely used organic ligands to attain atomically precise metal nanoclusters, while oxometalates as inorganic ligands have almost been neglected in this field. Here, we used oxometalates (e.g., MoO42- and WO42-) as protecting ligands along with phosphines, such as 1,4-bis(diphenylphosphino)butane (dppb), to design and synthesize a new class of silver nanoclusters including Ag28(dppb)6(MoO4)4, Ag28(dppb)6(WO4)4 and Ag32(dppb)12(MoO4)4(NO3)4. Each cluster consists of a two-shell Ag4@Ag24 core protected by 4 oxometalates. These clusters exhibit similar optical absorption and photoluminescence properties that are not dependent on surface ligands. Furthermore, the electronic structure analysis shows that the clusters are 20-electron "superatoms". This work demonstrates that oxometalates can play a key role in the formation of silver nanoclusters, and the effect of oxometalates should be considered in the design and synthesis of metal nanoclusters.

Genome-wide scan identifies opioid overdose risk locus close to MCOLN1.

The United States is experiencing the worst opioid overdose (OpOD) crisis in its history. We carried out a genome-wide association study on OpOD severity among 3 477 opioid-exposed individuals, 1 019 of whom experienced OpODs, including 2 032 European Americans (EAs) (653 overdose cases), and 1 445 African Americans (AAs) (366 overdose cases). Participants were scored 1 to 4 based on their reported overdose status and the number of times that medical treatment was required. Genome-wide association study (GWAS) of EAs and AAs separately resulted in two genome-wide significant (GWS) signals in AAs but none in EAs. The first signal was represented by three closely mapped variants (rs115208233, rs116181528, and rs114077267) located near mucolipin 1 (MCOLN1) and patatin-like phospholipase domain containing 6 (PNPLA6), and the other signal was represented by rs369098800 near dead-box helicase 18 (DDX18). There were no additional GWS signals in the trans-population meta-analysis, so that post-GWAS analysis focused on these loci. In network analysis, MCOLN1 was coexpressed with PNPLA6, but only MCOLN1-associated genes were enriched in functional categories relevant to OpOD, including calcium and cation channel activities; no enrichment was observed for PNPLA6-associated genes. Drug repositioning analysis was carried out in the connectivity map (CMap) database for MCOLN1 (PNPLA6 was not available in CMap) and showed that the opioid agonist drug-induced expression profile is similar to that of MCOLN1 overexpression and yielded the highest-ranked expression profile of 83 drug classes. Thus, MCOLN1 may be a risk gene for OpOD, but replication is needed. This knowledge could be helpful in the identification of drug targets for preventing OpOD.

Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.

Sex differences in opioid dependence (OD) are genetically influenced. We conducted genomewide gene-by-sex interaction scans for the DSM-IV diagnosis of OD in 8,387 African-American (AA) or European-American subjects (43.6% women; 4,715 OD subjects). Among AAs, 9 SNPs were genome-wide significant at ADGRV1 (adhesion G-protein-coupled receptor V1, lead-SNP rs2366929*(C/T), p = 1.5 × 10-9) for sex-different risk of OD, with the rs2366929*C-allele increasing OD risk only for men. The top co-expressions in brain were between ADGRV1 and GRIK2 in substantia nigra and medullary inferior olivary nucleus, and between ADGRV1 and EFHC2 in frontal cortex and putamen. Significant sex-differential ADGRV1 expression from GTEx was detected in breast (Bonferroni-corrected-p < 0.002) and in heart (p < 0.0125), with nominal significance identified in brain, thyroid, lung, and stomach (p < 0.05). ADGRV1 co-expression and disease-enrichment analysis identifying the top 10 diseases showed strikingly sexually dimorphic risks. The enrichment and transcriptome analyses provided convergent support that ADGRV1 exerts a sex-different effect on OD risk. This is the first study to identify genetic variants contributing to sex differences in OD. It shows that ADGRV1 contributes to OD risk only in AA men, a finding that warrants further study.

Direct Z-scheme La1-xCexMnO3 catalyst for photothermal degradation of toluene.

A series of Ce-doped LaMnO3 (La1-xCexMnO3) were prepared and were tested for gaseous toluene oxidation in order to investigate the effect of cerium doping in LaMnO3 on activity under photothermal conditions. It was found that the activity and CO2 yield of the catalyst can be effectively increased when x = 0.25. A group of characterization is used to characterize the morphology, composition, and physical properties of the as-prepared catalysts. Results show that the Ce-doped LaMnO3 can form coexistence of La1-xCexMnO3 and CeO2, the reaction of CeO2/La1-xCexMnO3 under photothermal conditions follows the Mars-van Krevelen redox cycle mechanism, and the prepared CeO2/La1-xCexMnO3 can form a highly efficient Z-scheme heterojunction, which can enhance the electrons transfer speed of the catalyst. Moreover, in the photothermal catalytic degradation, lattice oxygen is the most important active substance, a small amount of cerium doping can increase the lattice oxygen content of perovskite and increase the activity of the reaction.

pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds.

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

Covalent Functionalization of Bovine Serum Albumin with Graphene Quantum Dots for Stereospecific Molecular Recognition.

Stereospecific molecular recognition with simple and easily available proteins is of significant importance in life science and biomaterial science. Herein, we report on a chiral sensing platform, graphene quantum dots (GQDs)-functionalized bovine serum albumin (BSA), for chiral recognition of tryptophan (Trp) isomers. Amidation reaction between BSA and GQDs was directly responsible for the introduction of GQDs to BSA, resulting in significant changes in the spatial configuration of BSA and the exposure of more chiral sites at the protein surface. The BSA-GQDs-based chiral sensor exhibited good biomolecular homochirality in the recognition of Trp isomers, and the higher affinity of BSA-GQDs toward l-Trp than its isomer, d-Trp, was also revealed by density functional theory (DFT) considering the possible hydrogen bonds between the Trp isomers and the solvent-accessible residues of BSA.

GWAS and network analysis of co-occurring nicotine and alcohol dependence identifies significantly associated alleles and network.

Alcohol dependence (AD) and nicotine dependence (ND) co-occur frequently (AD+ND). We integrated SNP-based, gene-based, and protein-protein interaction network analyses to identify shared risk genes or gene subnetworks for AD+ND in African Americans (AAs, N = 2,094) and European Americans (EAs, N = 1,207). The DSM-IV criterion counts for AD and ND were modeled as two dependent variables in a multivariate linear mixed model, and analyzed separately for the two populations. The most significant SNP was rs6579845 in EAs (p < 1.29 × 10-8 ) in GM2A, which encodes GM2 ganglioside activator, and is a cis-expression quantitative locus that affects GM2A expression in blood and brain tissues. However, this SNP was not replicated in our another small sample (N = 678). We identified a subnetwork of 24 genes that contributed to the AD+ND criterion counts. In the gene-set analysis for the subnetwork in an independent sample, the Study of Addiction: Genetics and Environment project (predominately EAs), these 24 genes as a set differed in AD+ND versus control subjects in EAs (p = .041). Functional enrichment analysis for this subnetwork revealed that the gene enrichment involved primarily nerve growth factor pathways, and cocaine and amphetamine addiction. In conclusion, we identified a genome-wide significant variant at GM2A and a gene subnetwork underlying the genetic trait of shared AD+ND. These results increase our understanding of the shared (pleiotropic) genetic risk that underlies AD+ND.