Transgenic Arabidopsis thaliana plants expressing bacterial γ-hexachlorocyclohexane dehydrochlorinase LinA.

BACKGROUND: γ-Hexachlorocyclohexane (γ-HCH), an organochlorine insecticide of anthropogenic origin, is a persistent organic pollutant (POP) that causes environmental pollution concerns worldwide. Although many γ-HCH-degrading bacterial strains are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the low survival rate of the exogenous bacteria. Another strategy for the bioremediation of γ-HCH involves the use of transgenic plants expressing bacterial enzyme for γ-HCH degradation through phytoremediation. RESULTS: We generated transgenic Arabidopsis thaliana expressing γ-HCH dehydrochlroninase LinA from bacterium Sphingobium japonicum strain UT26. Among the transgenic Arabidopsis T2 lines, we obtained one line (A5) that expressed and accumulated LinA well. The A5-derived T3 plants showed higher tolerance to γ-HCH than the non-transformant control plants, indicating that γ-HCH is toxic for Arabidopsis thaliana and that this effect is relieved by LinA expression. The crude extract of the A5 plants showed γ-HCH degradation activity, and metabolites of γ-HCH produced by the LinA reaction were detected in the assay solution, indicating that the A5 plants accumulated the active LinA protein. In some A5 lines, the whole plant absorbed and degraded more than 99% of γ-HCH (10 ppm) in the liquid medium within 36 h. CONCLUSION: The transgenic Arabidopsis expressing active LinA absorbed and degraded γ-HCH in the liquid medium, indicating the high potential of LinA-expressing transgenic plants for the phytoremediation of environmental γ-HCH. This study marks a crucial step toward the practical use of transgenic plants for the phytoremediation of POPs.

Using TiO2 to capture hot electrons for self-powered position-sensitive photodetection.

As environmental issues arise, the demand for self-powered position-sensitive detectors (PSDs) is increasing because of their advantages in miniaturization and low power consumption. Finding higher efficiency schemes for energy conversion is paramount for realizing high-performance self-powered PSDs. Here, a surface plasmon-based approach was used to improve the energy conversion efficiency, and a plasmon-enhanced lateral photovoltaic effect (LPE) was observed in PSD with TiO2/Au nanorods (NRs)/Si structure. The Au NRs convert absorbed light energy into electricity by generating hot electrons, which are efficiently captured by the TiO2 layer, and the PSD is capable of generating position sensitivity as high as 251.75 mV/mm when illuminated by a 780 nm laser without any external power supply, i.e. about five times higher than similar sensors in previous studies. In addition, the position sensitivity can be tailored by the thickness of TiO2 films. The enhancement mechanism is investigated by a localized surface plasmon (LSP)-driven carrier diffusion model. These findings reveal an important strategy for high sensitivity and low energy cost PSDs while opening up new avenues for energy harvesting self-powered position sensors.

Dearomatization of [2.2]Paracyclophane-Derived N-Sulfonylimines through Cyclopropanation with Sulfur Ylides.

An unprecedented dearomatization of [2.2]paracyclophane-derived cyclic N-sulfonylimines was conducted through cyclopropanation with sulfur ylides, giving a series of dearomative cyclopropanes with good yields. DFT calculations suggested that the dearomatization was attributed to the relatively weak aromaticity of [2.2]paracyclophane derivatives that resulted from the effect of the unique [2.2]paracyclophane skeleton and the electron-withdrawing N-sulfonyl group. Some downstream elaborations of the products were demonstrated.

Cysteine Radical and Glutamate Collaboratively Enable C-H Bond Activation and C-N Bond Cleavage in a Glycyl Radical Enzyme HplG.

Hydroxyprolines are abundant in nature and widely utilized by many living organisms. Isomerization of trans-4-hydroxy-d-proline (t4D-HP) to generate 2-amino-4-ketopentanoate has been found to need a glycyl radical enzyme HplG, which catalyzes the cleavage of the C-N bond, while dehydration of trans-4-hydroxy-l-proline involves a homologous enzyme of HplG. Herein, molecular dynamics simulations and quantum mechanics/molecular mechanics (QM/MM) calculations are employed to understand the reaction mechanism of HplG. Two possible reaction pathways of HplG have been explored to decipher the origin of its chemoselectivity. The QM/MM calculations reveal that the isomerization proceeds via an initial hydrogen shift from the Cγ site of t4D-HP to a catalytic cysteine radical, followed by cleavage of the Cδ-N bond in t4D-HP to form a radical intermediate that captures a hydrogen atom from the cysteine. Activation of the Cδ-H bond in t4D-HP to bring about dehydration of t4D-HP possesses an extremely high energy barrier, thus rendering the dehydration pathway implausible in HplG. On the basis of the current calculations, conserved residue Glu429 plays a pivotal role in the isomerization pathway: the hydrogen bonding between it and t4D-HP weakens the hydroxyalkyl Cγ-Hγ bond, and it acts as a proton acceptor to trigger the cleavage of the C-N bond in t4D-HP. Our current QM/MM calculations rationalize the origin of the experimentally observed chemoselectivity of HplG and propose an H-bond-assisted bond activation strategy in radical-containing enzymes. These findings have general implications on radical-mediated enzymatic catalysis and expand our understanding of how nature wisely and selectively activates the C-H bond to modulate catalytic selectivity.

[CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar â disorder].

OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). METHODS: From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Sequential C-H Methylation Catalyzed by the B12 -Dependent SAM Enzyme TokK: Comprehensive Theoretical Study of Selectivities.

TokK is a B12 -dependent radical SAM enzyme involved in the biosynthesis of the ß-lactam antibiotic asparenomycin A. It can catalyze three methylations on different sp3 -hybridized carbon positions to introduce an isopropyl side chain at the ß-lactam ring of pantetheinylated carbapenem. Herein, we report a quantum chemical study of the reaction mechanism of TokK. A stepwise ''push-pull'' radical relay mechanism is proposed for each methylation: a 5'-deoxyadenosine radical first abstracts a hydrogen atom from the substrate in the active site, then methylcobalamin directionally donates a methyl group to the substrate. More importantly, calculations were able to uncover the origin of observed chemoselectivity and stereoselectivity for the first methylation and regioselectivity for the following two methylations. Further detailed distortion/interaction analysis can help to unravel the main factors controlling the selectivities. Our findings of sequential methylations by TokK could have profound implications for studying other B12 -dependent radical SAM enzymes.

Investigating Factors Influencing Medical Practitioners' Resistance to and Adoption of Internet Hospitals in China: Mixed Methods Study.

BACKGROUND: The swift shift toward internet hospitals has relied on the willingness of medical practitioners to embrace new systems and workflows. Low engagement or acceptance by medical practitioners leads to difficulties in patient access. However, few investigations have focused on barriers and facilitators of adoption of internet hospitals from the perspective of medical practitioners. OBJECTIVE: This study aims to identify both enabling and inhibiting predictors associated with resistance and behavioral intentions of medical practitioners to use internet hospitals by combining the conservation of resources theory with the Unified Theory of Acceptance and Use of Technology and technostress framework. METHODS: A mixed methods research design was conducted to qualitatively identify the factors that enable and inhibit resistance and behavioral intention to use internet hospitals, followed by a quantitative survey-based study that empirically tested the effects of the identified factors. The qualitative phase involved conducting in-depth interviews with 16 experts in China from June to August 2022. Thematic analysis was performed using the qualitative data analysis software NVivo version 10 (QSR International). On the basis of the findings and conceptual framework gained from the qualitative interviews, a cross-sectional, anonymous, web-based survey of 593 medical practitioners in 28 provincial administrative regions of China was conducted. The data collected were analyzed using the partial least squares method, with the assistance of SPSS 27.0 (IBM Corp) and Mplus 7.0 (Muthen and Muthen), to measure and validate the proposed model. RESULTS: On the basis of qualitative results, this study identified 4 facilitators and inhibitors, namely performance expectancy, social influence, work overload, and role ambiguity. Of the 593 medical practitioners surveyed in the quantitative research, most were female (n=364, 61.4%), had a middle title (n=211, 35.6%) or primary title (n=212, 35.8%), and had an average use experience of 6 months every year. By conducting structural equation modeling, we found that performance expectancy (ß=-.55; P<.001) and work overload (ß=.16; P=.005) had the most significant impact on resistance to change. Resistance to change fully mediated the influence of performance expectancy and partially mediated the influences of social influence (variance accounted for [VAF]=43.3%; P=.002), work overload (VAF=37.2%; P=.03), and role ambiguity (VAF=12.2%; P<.001) on behavioral intentions to use internet hospitals. In addition, this study found that the sex, age, professional title, and use experience of medical practitioners significantly moderated the aforementioned influencing mechanisms. CONCLUSIONS: This study investigated the factors that facilitate or hinder medical practitioners' resistance to change and their behavioral intentions to use internet hospitals. The findings suggest that policy makers avoid the resistance and further promote the adoption of internet hospitals by ensuring performance expectancy and social influence and eliminating work overload and role ambiguity.

Swietenine inhibited oxidative stress through AKT/Nrf2/HO-1 signal pathways and the liver-protective effect in T2DM mice: In vivo and in vitro study.

Swietenia macrophylla King, belongs to the Meliaceae family, is a valuable medicinal plant and its fruits have been processed commercially to a variety of health foods. The seeds have long been known for their ethnomedicinal significance against these diseases. Swietenine (Swi) was isolated from S. macrophylla and could ameliorate inflammation and oxidative stress. In this study, HepG2 cells induced by H2 O2 were used to construct oxidative stress model in vitro. The aim of this study was to investigate the protective effect of Swi on H2 O2 induced oxidative injury in HepG2 cells and its molecular mechanism, and to explore the effect of Swi on liver injury in db/db mice and its possible mechanism. The results showed that Swi significantly inhibited HepG2 cells viability and reduced oxidative damage in a dose-dependent manner as evidenced by a range of biochemical analysis and immunoblotting study. Moreover, it induced the protein and mRNA expression of HO-1 together with its upstream mediator Nrf2 and activated the phosphorylation of AKT in HepG2 cells. LY294002, a PI3K/AKT inhibitor, significantly suppressed the Nrf2 nuclear translocation and HO-1 expression in H2 O2 induced HepG2 cells treated with Swi. In addition, RNA interference with Nrf2 significantly reduced the expression level of Nrf2 and HO-1 in the nucleus. Swi has a significant protective effect on cell damage in H2 O2 induced HepG2 cells by increasing the antioxidant capacity which is achieved through the AKT/Nrf2/HO-1 pathway. Additionally, in vivo, Swi could protect the liver of type 2 diabetic mice by improving lipid deposition in liver tissue and inhibiting oxidative stress. These findings indicated that Swi can be a promising dietary agent to improve type 2 diabetes.

Transition-Metal-Free, Site-Selective C-F Arylation of Polyfluoroarenes via Electrophotocatalysis.

Direct CAr-F arylation is effective and sustainable for synthesis of polyfluorobiaryls with different degrees of fluorination, which are important motifs in medical and material chemistry. However, with no aid of transition metals, the engagement of CAr-F bond activation has proved difficult. Herein, an unprecedented transition-metal-free strategy is reported for site-selective CAr-F arylation of polyfluoroarenes with simple (het)arenes. By merging N,N-bis(2,6-diisopropylphenyl)perylene-3,4,9,10-bis(dicarboximide)-catalyzed electrophotocatalytic reduction and anodic nitroxyl radical oxidation in an electrophotocatalytic cell, various polyfluoroaromatics (2F-6F and 8F), especially inactive partially fluorinated aromatics, undergo sacrificial-reagents-free C-F bond arylation with high regioselectivity, and the yields are comparable to those for reported transition-metal catalysis. This atom- and step-economic protocol features a paired electrocatalysis with organic mediators in both cathodic and anodic processes. The broad substrate scope and good functional-group compatibility highlight the merits of this operationally simple strategy. Moreover, the easy gram-scale synthesis and late-stage functionalization collectively advocate for the practical value, which would promote the vigorous development of fluorine chemistry.

Facile Transformations of a Binuclear Cp*Co(II) Diamidonaphthalene Complex to Mixed-Valent Co(II)Co(III), Co(III)(µ-H)Co(III), and Co(III)(µ-OH)Co(III) Derivatives.

A diamido-bridged dicobalt complex supported by a diamidonaphthalene ligand, Cp*2Co2(µ-1,8-C10H8(NH)2) (1), was synthesized, and the reactivity relevant to redox transformations of the Co2N2 core was investigated. It was found that the Co(II)-Co(II) bond allows for protonation by [HPPh3][BF4] resulting in a bridging hydride, [1H]+, with pKa ∼ 7.6 in CH2Cl2. The diamidonaphthalene ligand can stabilize the binuclear system in the Co(II)Co(III) mixed-valent state (1+), which is capable of binding CO to afford [1-CO]+. Surprisingly, the mixed-valent complex also activates H2O to furnish a Co(III)Co(III) hydroxy complex [1-OH]+ accompanied by release of H2. The hydroxy ligand in [1-OH]+ is exchangeable, as demonstrated by 18O-labeling experiments on [1-OH]+ with H218O that led to the heavier isotopolog [1-18OH]+.

Natural swietenine attenuates diabetic nephropathy by regulating the NF-κB/NLRP3/Caspase-1 signaling pathways: In vivo and in vitro study.

Swietenine (Swi), isolated from Swietenia macrophylla King ameliorates inflammation and oxidative stress, and diabetic nephropathy has a close connection with them. So the effects of Swi on diabetic nephropathy and its mechanism of action was explored. We divided human mesangial cells into five groups and determined the expression of NF-κB and NLRP3 inflammasomes in each group. The levels of inflammatory factors IL-1ß and IL-18 were also measured. To explore the relationship between NF-κB and NLRP3, we added PDTC, a specific NF-κB inhibitor, and LPS, and divided the experimental groups into seven groups. We measured the expressions of NF-κB and NLRP3, and then added MCC950, a specific inhibitor of NLRP3 and LPS, the expression of NLRP3, Caspase-1, and IL-1ß and IL-18 were measured. Animals divided into four groups and administered over 8 weeks. Protein excretion, creatinine, urea nitrogen, and uric acid were measured. Swi down regulated the expression of NF-κB, NLRP3, and Caspase-1. It reduced the levels of IL-1ß and IL-18. PDTC decreased the expression of NF-κB and NLRP3. Compared with the HG + PDTC group, the expression of NF-κB and NLRP3 in the HG + Swi + PDTC group decreased significantly. After adding lipopolysaccharide, the expression of NF-κB and NLRP3 increased, but this situation was reversed after adding Swi. After adding LPS, the expression of NLRP3 and Caspase-1 increased, and the levels of IL-1ß and IL-18 also increased, but this situation was reversed after the addition of Swi. Swi significantly improved the renal function of mice with diabetic nephropathy and inhibited the activation of NF-κB and the NLRP3 inflammasome and reduced inflammation by regulating the NF-κB/NLRP3/Caspase-1 signaling pathway, thereby improving diabetic nephropathy.

Swietenine and swietenolide from Swietenia macrophylla king improve insulin secretion and attenuate apoptosis in H2 O2 induced INS-1 cells.

Oxidative stress is an important factor that causes pancreatic ß-cell dysfunction leading to the development and aggravation of diabetes. Swietenine (Stn) and swietenolide (Std) were isolated from the fruits of Swietenia macrophylla King and had the potential effects on treatment and prevention of diabetes. The aim of this study is to investigate the effects of Stn and Std on insulin secretion and apoptosis in H2 O2 induced insulinoma cell line (INS-1) cells. In the present study, INS-1 cells were treated with 300 µM H2 O2 for 4 h to establish the oxidative damage model. Cell apoptosis, insulin secretion, reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels, and Caspase-3 enzyme activity were measured via corresponding methods. Finally, pancreatic duodenal home box factor-1 (PDX-1), B cell lymphoma-2 (Bcl-2), and Bax protein expression were detected by western blot. Experimental results showed that Stn and Std could significantly improve the INS-1 cell viability, increase the secretion of insulin and reduce the ROS level in H2 O2 induced INS-1 cells. Furthermore, the SOD and GSH levels increased, and the MDA levels decreased compared with the model group after Stn and Std treatment. In addition, after treated with Stn and Std, cell apoptosis was improved, and the activity of Caspase 3 was also significantly inhibited. Meanwhile, Western blot results showed that Stn and Std could up-regulate the expression of PDX-1 protein, and affect the cell apoptosis pathway by up-regulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein. In conclusion, Stn and Std can signifcantly improve the insulin secretion function, protect oxidative stress injury, and reduce apoptosis in H2 O2 induced INS-1 cells, which provides a research basis for Stn and Std to be new drug candidates for the treatment and prevention of diabetes.

Plant begomoviruses subvert ubiquitination to suppress plant defenses against insect vectors.

Most plant viruses are vectored by insects and the interactions of virus-plant-vector have important ecological and evolutionary implications. Insect vectors often perform better on virus-infected plants. This indirect mutualism between plant viruses and insect vectors promotes the spread of virus and has significant agronomical effects. However, few studies have investigated how plant viruses manipulate plant defenses and promote vector performance. Begomoviruses are a prominent group of plant viruses in tropical and sub-tropical agro-ecosystems and are transmitted by whiteflies. Working with the whitefly Bemisia tabaci, begomoviruses and tobacco, we revealed that C2 protein of begomoviruses lacking DNA satellites was responsible for the suppression of plant defenses against whitefly vectors. We found that infection of plants by tomato yellow leaf curl virus (TYLCV), one of the most devastating begomoviruses worldwide, promoted the survival and reproduction of whitefly vectors. TYLCV C2 protein suppressed plant defenses by interacting with plant ubiquitin. This interaction compromised the degradation of JAZ1 protein, thus inhibiting jasmonic acid defense and the expression of MYC2-regulated terpene synthase genes. We further demonstrated that function of C2 protein among begomoviruses not associated with satellites is well conserved and ubiquitination is an evolutionarily conserved target of begomoviruses for the suppression of plant resistance to whitefly vectors. Taken together, these results demonstrate that ubiquitination inhibition by begomovirus C2 protein might be a general mechanism in begomovirus, whitefly and plant interactions.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

Revealing the Mechanism of Isethionate Sulfite-Lyase by QM/MM Calculations.

Isethionate sulfite-lyase (IseG) is a recently characterized glycyl radical enzyme (GRE) that catalyzes radical-mediated C-S bond cleavage of isethionate to produce acetaldehyde and sulfite. Herein, we use quantum mechanical/molecular mechanical (QM/MM) calculations to investigate the detailed catalytic reaction mechanism of IseG. Our calculations indicate that a previously proposed direct 1,2-elimination mechanism is disfavored. Instead, we suggest a new 1,2-migration mechanism for this enzymatic reaction: a key stepwise 1,2-SO3- radical migration occurs after the catalytically active cysteinyl radical grabs a hydrogen atom from isethionate, followed by hydrogen atom transfer from cysteine to a 1-hydroxylethane-1-sulfonate radical intermediate. Finally, the elimination of sulfite from 1-hydroxylethane-1-sulfonate to result in the final product is likely to occur outside the enzyme. Glu468 in the active site is found to help orient the substrate rather than grabbing a proton from the hydroxyl group of the substrate. Our findings help reveal the mechanisms of radical-mediated C-S bond cleavage of organosulfonates catalyzed by GREs and expand the understanding of radical-based enzymatic catalysis.

Identification of bipolar disorder using a combination of multimodality magnetic resonance imaging and machine learning techniques.

BACKGROUND: Bipolar disorder (BPD) is a common mood disorder that is often goes misdiagnosed or undiagnosed. Recently, machine learning techniques have been combined with neuroimaging methods to aid in the diagnosis of BPD. However, most studies have focused on the construction of classifiers based on single-modality MRI. Hence, in this study, we aimed to construct a support vector machine (SVM) model using a combination of structural and functional MRI, which could be used to accurately identify patients with BPD. METHODS: In total, 44 patients with BPD and 36 healthy controls were enrolled in the study. Clinical evaluation and MRI scans were performed for each subject. Next, image pre-processing, VBM and ReHo analyses were performed. The ReHo values of each subject in the clusters showing significant differences were extracted. Further, LASSO approach was recruited to screen features. Based on selected features, the SVM model was established, and discriminant analysis was performed. RESULTS: After using the two-sample t-test with multiple comparisons, a total of 8 clusters were extracted from the data (VBM = 6; ReHo = 2). Next, we used both VBM and ReHo data to construct the new SVM classifier, which could effectively identify patients with BPD at an accuracy of 87.5% (95%CI: 72.5-95.3%), sensitivity of 86.4% (95%CI: 64.0-96.4%), and specificity of 88.9% (95%CI: 63.9-98.0%) in the test data (p = 0.0022). CONCLUSIONS: A combination of structural and functional MRI can be of added value in the construction of SVM classifiers to aid in the accurate identification of BPD in the clinic.

Contribution of genes in the GABAergic pathway to bipolar disorder and its executive function deficit in the Chinese Han population.

In this study, we investigated the association between bipolar I disorder (BDI) and between cognitive deficits therein and SNPs in GABAergic receptor genes. The sample comprised 477 patients with BDI and 438 healthy controls, with three neurocognitive tests being administered in 123 patients and 164 controls. For three SNPs, rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, their allele frequencies were significantly different between patients and controls (Bonferroni-adjusted p = values 3.84 × 10-4 , 9.92 × 10-3 , and 1.22 × 10-2 , respectively). Four haplotypes were significantly associated with BDI (TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6, with p values of 0.0038, 0.044, 0.0176, and 0.0267, respectively, on 10,000 permutations). Furthermore, the SNP (rs2912585) within 250 kb upstream of the GABRB3 gene displayed a strong association with the Tower of Hanoi (TOH) executive time in the patient group (p = 2.844 × 10-6 ). One other SNP (rs754661), which is located at the intronic region of the same gene, was associated with the global trait of the executive function and post hoc analysis showed significant SNP by group effect (p = 0.0094). Our study supports previous findings that GABAA receptor genes are associated with bipolar disorder; it also suggests that the GABAA genes, especially the GABRB3 gene, might play a role in the executive function deficit in bipolar disorder, although future replication with a larger sample size is needed.

[Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population].

OBJECTIVE: To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population. METHODS: Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software. RESULTS: Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms. CONCLUSION: Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.

Factors Influencing the Intention of Chinese Adults to Recommend COVID-19 Vaccination for Specific or Non-Specific Groups.

The widespread availability of vaccines has profound implications for sustainable public health. Positive recommendation on vaccination is one of the most effective ways to increase the willingness to vaccinate against COVID-19. This study aims to investigate the factors influencing the intentions to recommend COVID-19 vaccination for specific groups (IRCVSG) and the intentions to recommend COVID-19 vaccination for non-specific groups (IRCVNSG) in China and explore the mediating role of vaccine hesitancy and perception of vaccination information. This study conducted a cross-sectional anonymous online survey of adults (N = 903) in 28 provincial-level administrative regions in China in May 2022. The prevalence of IRCVSG and IRCVNSG was 60.5% and 93.0%, respectively. Health information literacy has a significant direct and indirect impact on IRCVSG through safety hesitancy and the perceived adequacy and usefulness of vaccination information. The relationship between health information literacy and IRCVNSG is entirely mediated via hesitation about the effectiveness and perceived usefulness of vaccination information. Special attention should be paid to the safety hesitation of COVID-19 vaccination for specific groups. This study tests these effects from both theoretical and practical perspectives, helping to address barriers to promoting the vaccination of specific groups for COVID-19 in clinical practice, improving health and sustainability.