The dopamine transporter gene SLC6A3: multidisease risks.

The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region's functional markers such as DNPi (rs67175440) and 5'VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology.

Surface Enhancement Effects of Tiny SnO2 Nanoparticle Modification on α-Fe2O3 for Room-Temperature NH3 Sensing.

The development of a gas sensor capable of detecting ammonia with high selectivity and rapid response at room temperature has consistently posed a formidable challenge. To address this issue, the present study utilized a one-step solvothermal method to co-assemble α-Fe2O3 and SnO2 by evenly covering SnO2 nanoparticles on the surface of α-Fe2O3. By controlling the morphology and Fe/Sn mole ratio of the composite, the as-prepared sample exhibits high-performance detection of NH3. At room temperature conditions, a gas sensor composed of α-Fe2O3@3%SnO2 demonstrates a rapid response time of 14 s and a notable sensitivity of 83.9% when detecting 100 ppm ammonia. Experiments and density functional theory (DFT) calculations suggest that the adsorption capacity of α-Fe2O3 to ammonia is enhanced by the surface effect provided by SnO2. Meanwhile, the existence of SnO2 tailors the pore structure and effective surface area of α-Fe2O3, creating multiple channels for the diffusion and adsorption of ammonia molecules. Additionally, an N-N heterostructure is formed between α-Fe2O3 and SnO2, which enhances the potential energy barrier and improves the ammonia sensing performance. Demonstration experiments have proved that the sensor shows significant advantages over commercial sensors in the process of ammonia detection in agricultural facilities. This work provides new insights into the perspectives on ammonia detection at room temperature.

Does intramedullary nail have advantages over dynamic hip screw for the treatment of AO/OTA31A1-A3? A meta-analysis.

BACKGROUND: Hip fractures are still unsolved problems nowadays. We evaluated the functional outcomes and complications in the treatment of hip fractures (AO/OTA31A1-A3) to find potential difference and risk between intramedullary nail (IMN) and dynamic hip screw (DHS). METHOD: We searched PubMed, Embase, Cochrane library up to 19 June 2023 and retrieved any studies comparing IMN and DHS in treatment of Hip fractures. The main outcomes and complications were extracted from the included studies. The fixed-effect model was selected to pool the data for homogeneous studies (I2 < 50%). Otherwise, the random effects model was selected (heterogeneity, I2 > 50%). The analysis of sensitivity and subgroup was performed to explore the homogeneous studies among studies. The p-value of less than 0.05 was considered statistically significant. RESULTS: 30 RCT studies were included in this meta-analysis. There were significant difference of in the items of blood loss, screening time, femoral neck shortening, non-union, and femoral fractures (p < 0.05). Significant difference was found in the parameter of open reduction of fracture after sensitive analysis (p < 0.05). No significant difference was found in the parameter of Mobility Score at the last follow-up after sensitive analysis (p ≥ 0.05). There was no significant difference in the parameters of open reduction of fracture, required blood transfusion, mean surgical time, hospital stays, time to healing, mean Harris Hip Score, infection, cut out, poor reduction, breakage of implant, failure of fixation, reoperation, and systemic complications of chest infection, decubital ulcer, urinary tract infection and persistent pain in the hip (p ≥ 0.05). CONCLUSIONS: Our meta-analysis revealed that hip fractures treated with IMN have merits with lower rate of blood loss, femoral neck shortening and non-union; shortcoming of increased risk of femoral fractures. It is suggested that special attention should be paid to the risk of femoral fracture when intramedullary nail was inserted in the intraoperative.

Diet Control and Swimming Exercise Ameliorate HFD-Induced Cognitive Impairment Related to the SIRT1-NF-κB/PGC-1α Pathways in ApoE-/- Mice.

High-fat diet- (HFD-) induced neuroinflammation may ultimately lead to an increased risk of cognitive impairment. Here, we evaluate the effects of diet control and swimming or both on the prevention of cognitive impairment by enhancing SIRT1 activity. Twenty-week-old ApoE-/- mice were fed a HFD for 8 weeks and then were treated with diet control and/or swimming for 8 weeks. Cognitive function was assessed using the novel object recognition test (NORT) and Y-maze test. The expression of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B p65 (NF-κB p65), interleukin-1ß (IL-1ß), and tumour necrosis factor-α (TNF-α) in the hippocampus was measured by western blotting. The levels of fractional anisotropy (FA), N-acetylaspartate (NAA)/creatine (Cr) ratio, choline (Cho)/Cr ratio, and myo-inositol (MI)/Cr ratio in the hippocampus were evaluated by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) using 7.0-T magnetic resonance imaging (MRI). Our results showed that cognitive dysfunction and hippocampal neuroinflammation appeared to be remarkably observed in apolipoprotein E (ApoE)-/- mice fed with HFD. Diet control plus swimming significantly reversed HFD-induced cognitive decline, reduced the time spent exploring the novel object, and ameliorated spontaneous alternation in the Y-maze test. Compared with the HFD group, ApoE-/- mice fed diet control and/or subjected to swimming had an increase in FA, NAA/Cr, and Cho/Cr; a drop in MI/Cr; elevated expression levels of SIRT1, PGC-1α, and BDNF; and inhibited production of proinflammatory cytokines, including NF-κB p65, IL-1ß, and TNF-α. SIRT1, an NAD+-dependent class III histone enzyme, deacetylases and regulates the activity of PGC-1α and NF-κB. These data indicated that diet control and/or swimming ameliorate cognitive deficits through the inhibitory effect of neuroinflammation via SIRT1-mediated pathways, strongly suggesting that swimming and/or diet control could be potentially effective nonpharmacological treatments for cognitive impairment.

Alterations of white matter tracts and topological properties of structural networks in hemifacial spasm.

Hemifacial spasm (HFS) is characterized by involuntary and paroxysmal muscle contractions on the hemiface. It is generally believed that HFS is caused by neurovascular compression at the root exit zone of the facial nerve. In recent years, the structural alterations of brains with HFS have aroused growing concern. However, little attention has been directed towards the possible involvement of specific white matter (WM) tracts and the topological properties of structural networks in HFS. In the present study, diffusion magnetic resonance imaging tractography was utilized to construct structural networks and perform tractometric analysis. The diffusion tensor imaging scalar parameters along with the WM tracts, and the topological parameters of global networks and subnetworks, were assessed in 62 HFS patients and 57 demographically matched healthy controls (HCs). Moreover, we investigated the correlation of these parameters with disease-clinical-level (DCL) and disease-duration-time (DDT) of HFS patients. Compared with HCs, HFS patients had additional hub regions including the amygdala, ventromedial putamen, lateral occipital cortex, and rostral cuneus gyrus. Furthermore, HFS patients showed significant alternations with specific topological properties in some structural subnetworks, including the limbic, default mode, dorsal attention, somato-motor, and control networks, as well as diffusion properties in some WM tracts, including the superior longitudinal fasciculus, cingulum bundle, thalamo-frontal, and corpus callosum. These subnetworks and tracts were associated with the regulation of emotion, motor function, vision, and attention. Notably, we also found that the parameters with subnetworks and tracts exhibited correlations with DCL and DDT. In addition to corroborating previous findings in HFS, this study demonstrates the changed microstructures in specific locations along with the fiber tracts and changed topological properties in structural subnetworks.

Azole-Induced Color Vision Deficiency Associated with Thyroid Hormone Signaling: An Integrated In Vivo, In Vitro, and In Silico Study.

Azoles that are used in pesticides, pharmaceuticals, and personal care products can have toxic effects on fish. However, there is no information regarding azole-induced visual disorder associated with thyroid disruption. We evaluated changes in retinal morphology, optokinetic response, transcript abundance of the genes involved in color perception and hypothalamic-pituitary-thyroid (HPT) axis, and thyroid hormone (TH) levels in zebrafish larvae exposed to common azoles, such as climbazole (CBZ, 0.1 and 10 µg/L) and triadimefon (TDF, 50 and 500 µg/L), at environmentally relevant and predicted worst-case environmental concentrations. Subsequently, the effect of azoles on TH-dependent GH3 cell proliferation and thyroid receptor (TR)-regulated transcriptional activity, as well as the in silico binding affinity between azoles and TR isoforms, was investigated. Azole exposure decreased cell densities of the ganglion cell layer, inner nuclear layer, and photoreceptor layer. Zebrafish larvae exposed to environmentally relevant concentrations of CBZ and TDF showed a decrease in optokinetic response to green-white and red-white stripes but not blue-white stripes, consistent with disturbance in the corresponding opsin gene expression. Azole exposure also reduced triiodothyronine levels and concomitantly increased HPT-related gene expression. Molecular docking analysis combined with in vitro TR-mediated transactivation and dual-luciferase reporter assays demonstrated that CBZ and TDF exhibited TR antagonism. These results are comparable to those obtained from a known TR antagonist, namely, TR antagonist 1, as a positive control. Therefore, damage to specific color perception by azoles appears to result from lowered TH signaling, indicating the potential threat of environmental TH disruptors to the visual function of fish.

SMRT and Illumina RNA-Seq Identifies Potential Candidate Genes Related to the Double Flower Phenotype and Unveils SsAP2 as a Key Regulator of the Double-Flower Trait in Sagittaria sagittifolia.

Double flowers are one of the important objectives of ornamental plant breeding. Sagittaria sagittifolia is an aquatic herb in the Alismataceae family that is widely used as an ornamental plant in gardens. However, the reference genome has not been published, and the molecular regulatory mechanism of flower formation remains unclear. In this study, single molecule real-time (SMRT) sequencing technology combined with Illumina RNA-Seq was used to perform a more comprehensive analysis of S. sagittifolia for the first time. We obtained high-quality full-length transcripts, including 53,422 complete open reading frames, and identified 5980 transcription factors that belonged to 67 families, with many MADS-box genes involved in flower formation being obtained. The transcription factors regulated by plant hormone signals played an important role in the development of double flowers. We also identified an AP2 orthologous gene, SsAP2, with a deletion of the binding site for miR172, that overexpressed SsAP2 in S. sagittifolia and exhibited a delayed flowering time and an increased number of petals. This study is the first report of a full-length transcriptome of S. sagittifolia. These reference transcripts will be valuable resources for the analysis of gene structures and sequences, which provide a theoretical basis for the molecular regulatory mechanism governing the formation of double flowers.

Modern lifestyle risks associated with alcohol consumption and cigarette smoking in Ukraine.

Background: Substance uses confer huge risks for public health in modern society. This study aimed to evaluate current factors related to alcohol drinking and tobacco smoking in the republic of Ukraine. Methods: We distributed a questionnaire to healthy volunteers in four Ukrainian regions and collected 929 responses regarding demographic information, reasons for starting substance use, substance use family history, environmental factors, use pattern (internet, drinking or smoking), consequences of drinking, and insomnia. Linear regression and logistic regression analyses were performed to identify factors related to alcohol drinking and cigarette smoking. Results: Aging appeared to attenuate either drinking or smoking. To reduce school- or job-related stress, staying awake, peer pressure, friend-related issues, or to increase sexual desire and single parenting all would trigger drinking; male gender, family divorce, unhealthy diet and lack of awareness about harmful consequences were the main factors leading to smoking. Logistic regression suggested that education background, sleep problems, celebration events and lengthy internet work all could contribute to drinking. Conclusions: Various real-world factors related to substance uses were identified for the public of Ukraine. A validated instrument would help to identify risk factors in patients with substance use disorders.

Postpandemic Testing of Severe Acute Respiratory Syndrome Coronavirus 2 in the Huanan Seafood Market Area in Wuhan, China.

Seventy-six days after the coronavirus disease 2019 epidemic was contained in Wuhan, the Chinese government carried out a citywide severe acute respiratory syndrome coronavirus 2 nucleic acid testing initiative for all residents from 14 May to 1 June 2020. Our hospital tested 107 662 residents around Huanan seafood market, uncovering a positivity rate of 0.006%.

Chronic Exposure to Climbazole Induces Oxidative Stress and Sex Hormone Imbalance in the Testes of Male Zebrafish.

As the main active ingredient for the treatment of fungal infections, climbazole (CBZ) is commonly used in a variety of personal care products. After its use, CBZ enters the receiving environment directly or indirectly through domestic sewage. Its concentration can be up to several nanograms per liter in surface water. So far, the effects of CBZ on the reproductive system of female zebrafish have been systematically studied, but the potential toxicity mechanism of CBZ on male zebrafish still needs to be further explored. In this study, adult male zebrafish were exposed to CBZ at concentrations of 0.1, 10, and 1000 µg·L-1 for 28 days, and their testes were collected for histological, mass-spectrometry-based metabolomics, and biochemical analyses. We found that CBZ caused a significantly abnormal metabolism of purine and glutathione and triggered oxidative stress in zebrafish testes, thereby inducing testicular cell apoptosis. In addition, CBZ could inhibit the synthesis of essential sex hormones in the testis and thus reduce the sperm production. The conclusions of this study fill the data gap on the reproductive toxicity of CBZ to male zebrafish and highlight the ecotoxicological application of untargeted metabolomics in the biomarker discovery.

Orthorexia nervosa is associated with positive body image and life satisfaction in Chinese elderly: Evidence for a positive psychology perspective.

OBJECTIVE: Obsessive attention to healthy eating might paradoxically lead to physical and psychosocial impairments, a potential eating disorder termed orthorexia nervosa (ON). An ongoing debate concerns whether ON should be categorized as an eating disorder, an obsessive-compulsive disorder, or a mental disorder at all. A missing voice in this debate is ON in the elderly, which remains unknown, despite health being a more central issue in everyday life during old age. Similarly missing is ON in East Asia, which remains largely unexplored. METHOD: The current study investigated ON in 313 Chinese elderly (M = 67.90, SD = 7.94) using the Chinese version of the Düsseldorf Orthorexia Scale (C-DOS). Questionnaires were used to measure traditional eating disorder symptomatology, body image (body dissatisfaction, body appreciation, and functionality appreciation), lifestyle behaviors (fruit and vegetable consumption and time spent on physical activity), and indexes of well-being (psychological distress, food-related quality of life, and life satisfaction). RESULTS: ON symptoms were positively related to physical activity, fruit and vegetable (F&V) consumption, body appreciation, functionality appreciation, and life satisfaction, but negatively related to body dissatisfaction. Compared with those without ON, the elderly with ON scored higher on positive psychological/lifestyle measures but lower on negative psychological measures. DISCUSSION: Contrary to the dominant characterization of ON as a variant of disordered eating, in Chinese elderly ON was associated with several positive lifestyle and psychological measures. Thus, ON in the elderly might not be viewed as a form of disordered eating but can be protective and beneficial.

Reconfigurable and tunable terahertz wrench-shape metamaterial performing programmable characteristic.

A design of a tunable terahertz (THz) programmable device by using wrench-shape metamaterial (WSM) is presented, which is composed of a Au layer fabricated on a Si substrate. The size of the WSM unit cell is 30 µm×30 µm, and the distance between each WSM is 20 µm. The electromagnetic response of the THz programmable device exhibits the switch function for single-band resonance and dual-band resonance at the transverse electric mode and transverse magnetic mode. The resonance spans from 3.00 to 8.00 THz and is insensitive to the angle of the incident THz wave. While changing the incident angle of the THz wave, the bandwidth of the resonance becomes broader and the transmission spectrum decreases gradually. By configuring the unit cell from single-atom to quad-atom, WSM exhibits optical-logic behaviors with programmable characteristics and anti-interference. Such results are very suitable for use for an ultra-narrowband filter, single-/dual-band switch, polarization switch, and programmable device. It could potentially provide all-optical logical devices with multichannel data processing at higher bit rates.

Involvement of CB2 Receptors in the Neurobehavioral Effects of Catha Edulis (Vahl) Endl. (Khat) in Mice.

There is behavioral evidence for the interaction between crude khat extract and the endocannabinoid system, whereby the endocannabinoid system alters khat extract-mediated behavioral effects through modulation of the monoaminergic system. The objective of this study was to investigate the role of the endocannabinoid system on the neurobehavioral effect of khat extract in mice following concomitant administration of khat extract and the CB2R agonist, JWH133. Locomotor activity test, immunohistochemistry, and reverse transcriptase polymerase chain reaction technique were utilized to assess locomotor activity, tyrosine hydroxylase immunoreactivity, and expression of dopamine transporter mRNA gene. The results show sub-acute administration of khat extract alone increased locomotor activity in mice and co-administration of the CB2R agonist, JWH133, reduced khat extract induced hyperlocomotor activity. The data revealed that cell type specific deletion of CB2Rs on dopaminergic neurons increased the hyperlocomotor behavior of khat extract. Furthermore, the results revealed that khat extract attenuated MPTP induced motor deficits, which is enhanced by JWH133. Khat extract also increased expression of tyrosine hydroxylase positive cells and expression of dopamine transporter mRNA gene in wild type mice. Nevertheless, JWH133 did not alter the effect of khat extract on tyrosine hydroxylase immunoreactivity and dopamine transporter mRNA expression when given together with khat extract. Taken together, the results suggest that the CB2Rs selectively interact with khat extract-mediated locomotor effects and could be utilized as therapeutic target in central nervous system movement disorders associated with dopamine dysregulation.

The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder implicitly marked by the substantia nigra dopaminergic neuron degeneration and explicitly characterized by the motor and non-motor symptom complexes. Apart from the nigrostriatal dopamine depletion, the immune and endocrine study findings are also frequently reported, which, in fact, have helped to broaden the symptom spectrum and better explain the pathogenesis and progression of PD. Nevertheless, based on the neural, immune, and endocrine findings presented above, it is still difficult to fully recapitulate the pathophysiologic process of PD. Therefore, here, in this review, we have proposed the neuroimmunoendocrine (NIE) modulatory network in PD, aiming to achieve a more comprehensive interpretation of the pathogenesis and progression of this disease. As a matter of fact, in addition to the classical motor symptoms, NIE modulatory network can also underlie the non-motor symptoms such as gastrointestinal, neuropsychiatric, circadian rhythm, and sleep disorders in PD. Moreover, the dopamine (DA)-melatonin imbalance in the retino-diencephalic/mesencephalic-pineal axis also provides an alternative explanation for the motor complications in the process of DA replacement therapy. In conclusion, the NIE network can be expected to deepen our understanding and facilitate the multi-dimensional management and therapy of PD in future clinical practice.

[Effect of alisol A 24-acetate on proliferation of aorta smooth muscle cells in rats induced by ox-LDL].

Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown anti-atherosclerotic actions and many studies have proved that oxidized low density lipoprotein (Ox-LDL) could promote proliferation of aorta smooth muscle cells (VSMCs) which are closely related to atherosclerosis (AS). The purpose of this study was to evaluate the effect of alisol A 24-acetate on the proliferation of VSMCs isolated from the thoracic aorta of rats induced by ox-LDL. VSMCs were induced by ox-LDL(50 mg·L⁻¹) to establish the proliferation model and intervened by alisol A 24-acetate (5, 10, 20 mg·L⁻¹) for 12, 24 and 48 h. Then the proliferation of VSMCs was detected by MTT assay; protein expression levels of VSMCs PCNA, cyclinD1, cyclinE, p21, p27 and VSMCs PCNA, p21and p27 mRNA expression levels were detected by Western blot and Real-time polymerase chain reaction (RT-PCR) respectively. The results showed that ox-LDL could induce the proliferation of VSMCs (P<0.05), increase the protein expression levels of PCNA, cyclinD1 and cyclinE in the VSMCs (P<0.05) and inhibit the protein and mRNA expression levels of p21 and p27 (P<0.05). As compared with the model group, alisol A 24-acetate inhibited the proliferation of VSMCs in rats induced by ox-LDL and inhibited the protein expression of VSMCs PCNA, cyclinD1, cyclinE and enhanced the protein and mRNA p21 and p27 expression levels (P<0.05). The effect was more obvious with the increase of concentration of alisol A 24-acetate. These data indicate that alisol A 24-acetate can inhibit the proliferation of VSMCs induced by ox-LDL and the mechanism may be associated with inhibiting expression of cyclin protein, including cyclinD1, cyclinE, p21, p27 and so on.

Consciousness for perception and for action: A perspective from unconscious binding.

I argue that the scope and strength of unconscious perception have been overestimated in extant theories. I describe an unconscious binding perspective, and how in conjunction with rigorous methodology it can guide the delineation of unconscious processing. Under this perspective, the function of consciousness is to increase the saliency of conscious contents by facilitating the deployment of focal attention.

Lithium protects dopaminergic cells from rotenone toxicity via autophagy enhancement.

BACKGROUND: Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson's disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated. RESULTS: Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 µM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 µM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy). CONCLUSIONS: These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD.

More power to the unconscious: conscious, but not unconscious, exogenous attention requires location variation.

Substantial evidence suggests that unconscious processing can be characterized as a lesser or weaker version of conscious processing. To test this notion, we designed a novel repeated-cuing procedure based on exogenous attention: The location of the attentional cue was first fixed across blocks (fixed-cue blocks), and then the cue was removed in subsequent blocks (no-cue blocks). The visibility of the cue was also manipulated. We found that when the cue was invisible, the response to a prespecified stimulus in the fixed-cue blocks was faster if the stimulus was at the cued location than if it was at the uncued location. But when the cue was visible, this cuing effect was abolished, potentially because of an awareness-dependent, location-based inhibition mechanism, as revealed by an attentional bias against the previously cued location in the no-cue blocks. We call this bias negative attentional aftereffect. These results provide novel evidence against the weaker-version characterization of unconscious effects, highlighting dissociable components of orienting and inhibition in exogenous cuing through awareness and temporal dynamics.