Deep integration of metabolome and transcriptome characterizes alkaloid metabolism in Houttuynia cordata.

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.

Water deprivation modifies the metabolic profile of lavender (Lavandula angustifolia Mill.) leaves.

Lavender plantation is globally expanded due to the increasing demand of its essential oil and its popularity as an ornamental species. However, lavender plantations, and consequently essential oil industries, are threatened by more frequent and severe drought episodes in a globally changing climate. Still little is known about the changes in the general metabolome, which provides the precursors of essential oil production, by extended drought events. Prolonged drought fundamentally results in yield losses and changing essential oil composition. In the present study, the general metabolome of a main cultivated lavender species (Lavandula angustifolia Mill.) in response to water deprivation (WD) and re-watering was analyzed to identify the metabolomics responses. We found prolonged WD resulted in significant accumulations of glucose, 1,6-anhydro-ß-D-glucose, sucrose, melezitose and raffinose, but declines of allulose, ß-D-allose, altrose, fructose and D-cellobiose accompanied by decreased organic acids abundances. Amino acids and aromatic compounds of p-coumaric acid, hydrocaffeic acid and caffeic acid significantly accumulated at prolonged WD, whereas aromatics of cis-ferulic acid, taxifolin and two fatty acids (i.e., palmitic acid and stearic acid) significantly decreased. Prolonged WD also resulted in decreased abundances of polyols, particularly myo-inositol, galactinol and arabitol. The altered metabolite profiles by prolonged WD were mostly not recovered after re-watering, except for branched-chain amino acids, proline, serine and threonine. Our study illustrates the complex changes of leaf primary and secondary metabolic processes of L. angustifolia by drought events and highlights the potential impact of these precursors of essential oil production on the lavender industry.

Know When You Are Too Many: Density-Dependent Release of Pheromones During Host Colonisation by the European Spruce Bark Beetle, Ips typographus (L.).

Individuals across various animal species communicate their presence to conspecifics. Especially phytophagous and parasitoid insects with their brood developing on limited resources rely on chemical cues, such as host-marking pheromones, to reduce intraspecific competition. Bark beetles are phytophagous insects with some species being economically and ecologically relevant forest pests. Several of them use the volatile compound verbenone to inhibit attraction and reduce intraspecific competition. However, in the Eurasian spruce bark beetle, Ips typographus (L.), temporal emission patterns did so far not quite support the putative function of verbenone as an indicator of densely colonised host trees. More importantly, it is currently unclear how well verbenone emission is actually related to colonisation density and thus intraspecific competition. Here, we inoculated Norway spruce logs with I. typographus at two defined colonisation densities in the greenhouse and measured the emission of verbenone and its precursors α-pinene and verbenol over time. Verbenone emission was 3-7 times greater from colonised logs compared to decaying logs without beetles during the major part of larval development. Furthermore, our data supports the quantitative hypothesis, that the termination of attack on a tree is mediated by a cessation of the release of verbenol and continuous emission of verbenone. The latter is most likely a passively produced host-marking cue reflecting the actual density of conspecifics since per-beetle emission was unaffected by colonisation density. These findings shed new light on the regulation of bark beetle mass aggregations, which are currently causing previously unseen economic damages in temperate forests.

DNMT1 SNPs (rs2114724 and rs2228611) associated with positive symptoms in Chinese patients with schizophrenia.

OBJECTIVE: Schizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia. METHODS: The study was case-control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy-Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed. RESULTS: There were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724-rs 2228611 was complete linkage disequilibrium, and rs 1569686-rs 2424908, rs 2424932-rs 1569696 and rs 2424932-rs 2424908 were strongly linkage disequilibrium. CONCLUSION: The polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

Physiological responses of date palm (Phoenix dactylifera) seedlings to seawater and flooding.

In their natural environment along coast lines, date palms are exposed to seawater inundation and, hence, combined stress by salinity and flooding. To elucidate the consequences of this combined stress on foliar gas exchange and metabolite abundances in leaves and roots, date palm seedlings were exposed to flooding with seawater and its major constituents under controlled conditions. Seawater flooding significantly reduced CO2 assimilation, transpiration and stomatal conductance, but did not affect isoprene emission. A similar effect was observed upon NaCl exposure. By contrast, flooding with distilled water or MgSO4 did not affect CO2 /H2 O gas exchange or stomatal conductance significantly, indicating that neither flooding itself, nor seawater sulfate, contributed greatly to stomatal closure. Seawater exposure increased Na and Cl contents in leaves and roots, but did not affect sulfate contents significantly. Metabolite analyses revealed reduced abundances of foliar compatible solutes, such as sugars and sugar alcohols, whereas nitrogen compounds accumulated in roots. Reduced transpiration upon seawater exposure may contribute to controlling the movement of toxic ions to leaves and, therefore, can be seen as a mechanism to cope with salinity. The present results indicate that date palm seedlings are tolerant towards seawater exposure to some extent, and highly tolerant to flooding.

Molecular and physiological characterization of the monosaccharide transporters gene family in Medicago truncatula.

Monosaccharide transporters (MSTs) represent key components of the carbon transport and partitioning mechanisms in plants, mediating the cell-to-cell and long-distance distribution of a wide variety of monosaccharides. In this study, we performed a thorough structural, molecular, and physiological characterization of the monosaccharide transporter gene family in the model legume Medicago truncatula. The complete set of MST family members was identified with a novel bioinformatic approach. Prolonged darkness was used as a test condition to identify the relevant transcriptomic and metabolic responses combining MST transcript profiling and metabolomic analysis. Our results suggest that MSTs play a pivotal role in the efficient partitioning and utilization of sugars, and possibly in the mechanisms of carbon remobilization in nodules upon photosynthate-limiting conditions, as nodules are forced to acquire a new role as a source of both C and N.

Climate and development modulate the metabolome and antioxidative system of date palm leaves.

Date palms are remarkably tolerant to environmental stresses, but the mechanisms involved remain poorly characterized. Leaf metabolome profiling was therefore performed on mature (ML) and young (YL) leaves of 2-year-old date palm seedlings that had been grown in climate chambers that simulate summer and winter conditions in eastern Saudi Arabia. Cultivation under high temperature (summer climate) resulted in higher YL H2O2 leaf levels despite increases in dehydroascorbate reductase (DHAR) activities. The levels of raffinose and galactinol, tricarboxylic acid cycle intermediates, and total amino acids were higher under these conditions, particularly in YL. The accumulation of unsaturated fatty acids, 9,12-octadecadienoic acid and 9,12,15-octadecatrienoic acid, was lower in ML. In contrast, the amounts of saturated tetradecanoic acid and heptadecanoic acid were increased in YL under summer climate conditions. The accumulation of phenolic compounds was favored under summer conditions, while flavonoids accumulated under lower temperature (winter climate) conditions. YL displayed stronger hydration, lower H2O2 levels, and more negative δ 13C values, indicating effective reactive oxygen species scavenging. These findings, which demonstrate the substantial metabolic adjustments that facilitate tolerance to the high temperatures in YL and ML, suggest that YL may be more responsive to climate change.

Strategies of plants to overcome abiotic and biotic stresses.

In their environment, plants are exposed to a multitude of abiotic and biotic stresses that differ in intensity, duration and severity. As sessile organisms, they cannot escape these stresses, but instead have developed strategies to overcome them or to compensate for the consequences of stress exposure. Defence can take place at different levels and the mechanisms involved are thought to differ in efficiency across these levels. To minimise metabolic constraints and to reduce the costs of stress defence, plants prioritise first-line defence strategies in the apoplastic space, involving ascorbate, defensins and small peptides, as well as secondary metabolites, before cellular processes are affected. In addition, a large number of different symplastic mechanisms also provide efficient stress defence, including chemical antioxidants, antioxidative enzymes, secondary metabolites, defensins and other peptides as well as proteins. At both the symplastic and the apoplastic level of stress defence and compensation, a number of specialised transporters are thought to be involved in exchange across membranes that still have not been identified, and information on the regeneration of different defence compounds remains ambiguous. In addition, strategies to overcome and compensate for stress exposure operate not only at the cellular, but also at the organ and whole-plant levels, including stomatal regulation, and hypersensitive and systemic responses to prevent or reduce the spread of stress impacts within the plant. Defence can also take place at the ecosystem level by root exudation of signalling molecules and the emission of volatile organic compounds, either directly or indirectly into the rhizosphere and/or the aboveground atmosphere. The mechanisms by which plants control the production of these compounds and that mediate perception of stressful conditions are still not fully understood. Here we summarise plant defence strategies from the cellular to ecosystem level, discuss their advantages and disadvantages for plant growth and development, elucidate the current state of research on the transport and regeneration capacity of defence metabolites, and outline insufficiently explored questions for further investigation.

The interaction of RELN-DNMT genes involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility.

OBJECTIVE: Schizophrenia belongs to a severe mental illness with complicated clinical presentations, an ill-defined pathogenesis, and no known cause. Many genetic studies imply that polygenic interaction is important in the development of schizophrenia. The main mechanism of the RELN-BDNF-CREB-DNMT signaling pathway in neurodevelopment involves RELN, brain-derived neurotrophic factor (BDNF), transcription factor cyclic adenosine monophosphate response element binding protein (CREB), DNA methyltransferase 1 (DNMT1), as well as DNA methyltransferase 3B (DNMT3B). An early case-control research on 15 polymorphisms in the RELN, CREB, BDNF, DNMT1, and DNMT3B genes was done. A single gene variation has little effect on the pathogenesis of schizophrenia, but the combination of intergenic variation loci has a bigger impact because schizophrenia is a complex polygenic disorder. The objective of the current study sought to explore the impact of genetic interactions between RELN, BDNF, CREB, DNMT1, and DNMT3B on schizophrenia in order to further highlight the genetic factors influencing the risk of schizophrenia. METHODS: Taking the case-control study design, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to be the evaluation norm, 134 individuals suffering from schizophrenia hospitalized in the Third People's Hospital of Zhongshan City within January 2018 to April 2020 (case group) were selected, and 64 healthy individuals (control group) from the same geographical area had been chosen as well. MassArray identified DNMT1 gene single nucleotide polymorphisms (rs2114724 and rs2228611) and DNMT3B gene SNPs (rs2424932, rs1569686, rs6119954, and rs2424908). Using the generalized multifactor dimensionality reduction (GMDR), the RELN-BDNF-CREB-DNMT pathway's gene interactions were examined for their impact on schizophrenia. RESULTS: GMDR analysis showed that the three-order interaction model RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) was the optimal model (p = 0.001), with the consistency of cross-validation of 10/10 and the test accuracy of 0.8711. CONCLUSION: The interaction between the RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) may be related to schizophrenia, and large sample sizes should be verified in different population.

Integrative multi-omics analyses of date palm (Phoenix dactylifera) roots and leaves reveal how the halophyte land plant copes with sea water.

Date palm (Phoenix dactylifera L.) is able to grow and complete its life cycle while being rooted in highly saline soils. Which of the many well-known salt-tolerance strategies are combined to fine-tune this remarkable resilience is unknown. The precise location, whether in the shoot or the root, where these strategies are employed remains uncertain, leaving us unaware of how the various known salt-tolerance mechanisms are integrated to fine-tune this remarkable resilience. To address this shortcoming, we exposed date palm to a salt stress dose equivalent to seawater for up to 4 weeks and applied integrative multi-omics analyses followed by targeted metabolomics, hormone, and ion analyses. Integration of proteomic into transcriptomic data allowed a view beyond simple correlation, revealing a remarkably high degree of convergence between gene expression and protein abundance. This sheds a clear light on the acclimatization mechanisms employed, which depend on reprogramming of protein biosynthesis. For growth in highly saline habitats, date palm effectively combines various salt-tolerance mechanisms found in both halophytes and glycophytes: "avoidance" by efficient sodium and chloride exclusion at the roots, and "acclimation" by osmotic adjustment, reactive oxygen species scavenging in leaves, and remodeling of the ribosome-associated proteome in salt-exposed root cells. Combined efficiently as in P. dactylifera L., these sets of mechanisms seem to explain the palm's excellent salt stress tolerance.

Cortical thickness and intrinsic activity changes in middle-aged men with alcohol use disorder.

BACKGROUND: Previous studies reported the alterations of brain structure or function in people with alcohol use disorder (AUD). However, a multi-modal approach combining structural and functional studies is essential to understanding the neural mechanisms of AUD. Hence, we examined regional differences in cortical thickness (CT) and amplitude of low-frequency fluctuation (ALFF) in patients with AUD. METHODS: Thirty male patients with AUD and thirty age- and education-matched healthy male controls were recruited. High-resolution anatomical and resting-state functional MRI (rs-fMRI) data were collected, and the CT and ALFF were computed. RESULTS: Behaviorally, males with AUD showed a cognitive decline in multiple domains. Structurally, they presented prominent reductions in CT in the bilateral temporal, insular, precentral, and dorsolateral prefrontal gyri (p < 0.05, voxel-wise family-wise error [FWE]). Functionally, a significant decrease in ALFF in the bilateral temporal, dorsolateral prefrontal, insular, putamen, cerebellum, right precuneus, mid-cingulate, and precentral gyri were observed (p < 0.05, FWE). CONCLUSIONS: Our findings demonstrate the dual alterations of alcohol-related brain structure and function in male patients with AUD. These results may be useful in understanding the neural mechanisms in AUD.

Differences of nitrogen metabolism in date palm (Phoenix dactylifera) seedlings subjected to water deprivation and salt exposure.

Drought and salt exposure are among the most prevalent and severe abiotic stressors causing serious agricultural yield losses, alone and in combination. Little is known about differences and similarities in the effects of these two stress factors on plant metabolic regulation, particularly on nitrogen metabolism. Here, we studied the effects of water deprivation and salt exposure on water relations and nitrogen metabolites in leaves and roots of date palm seedlings. Both, water deprivation and salt exposure had no significant effects on plant water content or stable carbon (C) and nitrogen (N) isotope signatures. Significant effects of water deprivation on total C and N concentrations were only observed in roots, i.e., decreased total C and increased total N concentrations. Whereas salt exposure initially decreased total C and increased total N concentrations significantly in roots, foliar total C concentration was increased upon prolonged exposure. Initially C/N ratios declined in roots of plants from both treatments and upon prolonged salt exposure also in the leaves. Neither treatment affected soluble protein and structural N concentrations in leaves or roots, but resulted in the accumulation of most amino acids, except for glutamate and tryptophan, which remained stable, and serine, which decreased, in roots. Accumulation of the most abundant amino acids, lysine and proline, was observed in roots under both treatments, but in leaves only upon salt exposure. This finding indicates a similar role of these amino acids as compatible solutes in the roots in response to salt und drought, but not in the leaves. Upon prolonged treatment, amino acid concentrations returned to levels found in unstressed plants in leaves of water deprived, but not salt exposed, plants. The present results show both water deprivation and salt exposure strongly impact N metabolism of date palm seedlings, but in a different manner in leaves and roots.

Uncovering nutritional metabolites and candidate genes involved in flavonoid metabolism in Houttuynia cordata through combined metabolomic and transcriptomic analyses.

The perennial herb Houttuynia cordata has long been cultivated and used as medicinal and edible plant in Asia. Nowadays, increasing attention is attracted due to its numerous health benefits. Flavonoids are the main chemical constituents exerting pharmacological activities. In the present study, we investigated both metabolome and transcriptome of two H. cordata accessions (6# and 7#) with distinct flavonoids contents. In total 397 metabolites, i.e., 220 flavonoids, 92 amino acids and derivatives, 20 vitamins, and 65 saccharides were abundant in aboveground part. Cyanidin-3-O-rutinoside and quercetin-3-O-galactoside were the most abundant flavonoids, which can be categorized into seven classes, namely anthocyanidins, chalcones, flavanols, flavanones, flavanonols, flavones, and flavonols. Flavonols was the most abundant group. Contents of 112 flavonoids differed significantly between the two accessions, with catechin-(7,8-bc)-4α-(3,4-dihydroxyphenyl)-dihydro-2-(3H)-one, cinchonain Id, and cinchonain Ic being the dominant flavonoid metabolites among them. Pinocembrin-7-O-neohesperidoside, pinocembrin-7-O-rutinoside, and kaempferol-3-O-galactoside-4'-O-glucoside were uniquely abundant in accession 7. Transcriptome data revealed a total of 110 different expressed genes related to flavonoid metabolism, with more highly expressed genes observed in 7#. We annotated a total of 19 differential flavonoid metabolites and 34 differentially expressed genes that are associated with the flavonoid metabolic network. Based on the transcriptome and qPCR data a total of 8 key candidate genes involved in flavonoid metabolism were identified. The ANS gene were found to play an important role in the synthesis of cyanidin-3-O-glucoside, while the CHI, F3'H and FLS genes were mainly responsible for controlling the levels of flavanones, flavones, and flavonols, respectively. Collectively, the present study provides important insights into the molecular mechanism underlying flavonoid metabolism in H. cordata.

A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia.

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia. Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People's Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms. Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p < 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p < 0.05). Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.

The mechanisms and prediction of non-structural carbohydrates accretion and depletion after mechanical wounding in slash pine (Pinus elliottii) using near-infrared reflectance spectroscopy.

BACKGROUND: The allocation of non-structural carbohydrates (NSCs) plays a critical role in the physiology and metabolism of tree growth and survival defense. However, little is known about the allocation of NSC after continuous mechanical wounding of pine by resin tapping during tree growth. RESULTS: Here, we examine the NSC allocation in plant tissues after 3 year lasting resin tapping, and also investigate the use of near-infrared reflectance (NIR) spectroscopy to quantify the NSC, starch and free sugar (e.g., sucrose, glucose, and fructose) concentrations in different plant tissues of slash pine. Spectral measurements on pine needle, branch, trunk phloem, and root were obtained before starch and free sugar concentrations were measured in the laboratory. The variation of NSC, starch and free sugars in different plant tissues after resin tapping was analyzed. Partial least squares regression was applied to calibrate prediction models, models were simulated 100 times for model performance and error estimation. More NSC, starch and free sugars were stored in winter than summer both in tapped and control trees. The position of resin tapping significantly influenced the NSCs allocation in plant tissues: more NSCs were transformed into free sugars for defensive resin synthesis close to the tapping wound rather than induced distal systemic responses. Models for predicting NSC and free sugars of plant tissues showed promising results for the whole tree for fructose (R2CV = 0.72), glucose (R2CV = 0.67), NSCs (R2CV = 0.66) and starch (R2CV = 0.58) estimates based on NIR models. Models for individual plant tissues also showed reasonable predictive ability: the best model for NSCs and starch prediction was found in root. The significance multivariate correlation algorithm for variable selection significantly reduced the number of variables. Important variables were identified, including features at 1021-1290 nm, 1480, 1748, 1941, 2020, 2123 and 2355 nm, which are highly related to NSC, starch, fructose, glucose and sucrose. CONCLUSIONS: NIR spectroscopy provided a rapid and cost-effective method to monitor NSC, starch and free sugar concentrations after continuous resin tapping. It can be used for studying the trade-off between growth and production of defensive metabolites.

Naloxone Alleviate the Severity of Delirium in Hospitalized Patients With Parkinsonism: Three Case Reports.

Purpose: Delirium is common in geriatric with Parkinson's disease (PD). Treatments for delirium have generally been neuroleptics; however, antipsychotics have potential effect to block striatal dopamine D2 receptors and worsen symptom of parkinsonism. We explored whether naloxone can alleviate delirium in PD and other forms of parkinsonism. Patients and Methods: Patients with parkinsonism who met the delirium criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) received naloxone infusions once or twice daily. Treatment effects were evaluated by the delirium rating scale-revised 98 (DRS-R98), including non-cognitive and cognitive subscales; the Richmond agitation-sedation scale (RASS); and the mini mental status examination (MMSE). Results: Two patients with primary parkinsonism, one with vascular PD were observed. The daily dose of naloxone was 2.08 ± 0.64 mg (range: 1-4 mg). Medication time last from 1 h to 7 days without side effects observed. Following with naloxone infusions, DRS-R98 scores decreased within 12 h and MMSE scores increased. The psychotic symptoms, disorientation, and attention deficits were alleviated significantly, while RASS scores decreased with naloxone treatment. Conclusion: Naloxone alleviated psychotic symptoms, improved cognitive dysfunction, and irritability in patients with delirium in the context of PD. The preliminary findings point out that the opioid system may be involved in the pathophysiology of delirium, which may be one of potential treat targets for delirium of PD.

Intrinsic dialogues between the two hemispheres in middle-aged male alcoholics: a resting-state functional MRI study.

BACKGROUND: The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics. METHODS: Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis. RESULTS: We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems. CONCLUSIONS: Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.

Prevalence and risk factors for mental health symptoms in community epidemic prevention workers during the postpandemic era of COVID-19 in China.

Few people have paid attention to community epidemic prevention workers in the postpandemic era of COVID-19. This study aimed to explore the prevalence and risk factors for mental health symptoms in community epidemic prevention workers during the postpandemic era. Mental health status was evaluated by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Chinese Perceived Stress Scale, Insomnia Severity Index, and Maslach Burnout Inventory-General Survey. The results showed that a considerable proportion of community epidemic prevention workers reported symptoms of depression (39.7%), anxiety (29.5%), high stress (51.1%), insomnia (30.8%), and burnout (53.3%). The prevalence of depression and anxiety in community epidemic prevention workers was higher than in community residents. Among community epidemic prevention workers, short sleep duration was a risk factor for depression, anxiety, high stress and insomnia. Concurrent engagement in work unrelated to epidemic prevention and current use of hypnotics were risk factors for depression, anxiety and insomnia. Our study suggests that during the postpandemic era, the mental health problems of community epidemic prevention workers are more serious than those of community residents. Several variables, such as short sleep duration and concurrent engagement in work unrelated to epidemic prevention, are associated with mental health among community epidemic prevention workers.