Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Strain-level structure of gut microbiome showed potential association with cognitive function in major depressive disorder: A pilot study.

BACKGROUND: Although the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether gut microbiota affects cognitive function in patients with MDD. In this study, we explored the association between gut microbiota and cognitive function in MDD and its possible mechanisms. METHODS: We enrolled 57 patients with MDD and 30 healthy controls (HCs) and used 16S rRNA gene sequencing analysis and shotgun metagenomic sequencing analysis to determine gut microbial composition. RESULTS: The richness and diversity of gut microbiota in patients with MDD were the same as those in HCs, but there were differences in the abundance of Bifidobacterium and Blautia. Compared with HCs, two strains (bin_32 and bin_55) were significantly increased, and one strain (bin_31) was significantly decreased in patients with MDD based on the strain-level meta-analysis. Time to complete the Stroop-C had significant negative correlations with bin_31 and bin_32. Bin_55 had significant negative correlations with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 s but significant positive correlations with correct answers in 120 s on the Stroop-CW. LIMITATIONS: This study only tested the cognitive function of MDD in a small sample, which may have caused some bias. CONCLUSIONS: Based on our strain-level analysis, we found that gut microbiota may be associated with the pathogenesis of MDD and may have potential effects on cognitive function.

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder.

Background: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD. Methods: A total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein-protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway. Results: Our analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress. Conclusion: These results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD.

Effect of Radial Artery Compression with a Novel Automatic Pressure-Controlled Radial Compression Device: A Short-Term Prospective Interventional Pilot Study.

This study was conducted to design a novel radial compression device with the function of automatic pressure control and evaluate the feasibility and safety of this new technique. Patients who underwent transradial access (TRA) coronary angiography and percutaneous coronary intervention (PCI) in the First Hospital of Jiaxing between August 2021and October 2021 were prospectively enrolled in this pilot interventional study. The patients were grouped in a 1 : 1 ratio to receive compression with a novel device (the experimental group) or a conventional device without pressure control (the control group). The primary endpoint was the compression time, and the main secondary endpoints were rebleeding, upper-limb swelling, radial artery occlusion (RAO), and device-related pressure injury (DPI). Eighty-four patients were enrolled in this study. No significant differences were found in the baseline clinical characteristics between the two groups. Compared with the control group, the compression time in the experimental group was significantly reduced (207.4 ± 15.5 vs. 378.1 ± 19 min, p < 0.001). Besides, the rate of upper-limb swelling was also significantly lower in the novel device group (2.4% vs. 85.7%, p < 0.001), as well as the rate of DPI (19.05% vs. 100%, p = 0.005). Furthermore, the pain score in the experimental group was significantly lower than in the control group (0.79 ± 0.42 vs. 1.83 ± 0.58, p < 0.001). There were no significant differences in the rate of rebleeding (7.1% vs. 14.3, p = 0.48) between the two groups. In addition, no RAO occurred in any of the groups. The novel automatic pressure-controlled radial compression device could reduce the hemostasis time and decrease the rate of adverse complications. It might be a promising and effective compression device in TRA coronary invasive procedures.

The mitochondrial genomes of the Geometroidea (Lepidoptera) and their phylogenetic implications.

The Geometroidea is a large superfamily of Lepidoptera in species composition and contains numerous economically important pest species that cause great loss in crop and forest production. However, understanding of mitogenomes remains limited due to relatively fewer mitogenomes previously reported for this megadiverse group. Here, we sequenced and annotated nine mitogenomes for Geometridae and further analyzed the mitogenomic evolution and phylogeny of the whole superfamily. All nine mitogenomes contained 37 mitochondrial genes typical in insects, and gene organization was conserved except for Somatina indicataria. In S. indicataria, the positions of two tRNAs were rearranged. The trnR was located before trnA instead of after trnA typical in Lepidoptera, whereas the trnE was detected rarely on the minority strand (N-strand). This trnR-trnA-trnN-trnS1-trnE-trnF newly recognized in S. indicataria represents the first gene rearrangement reported for Geometroidea and is also unique in Lepidoptera. Besides, nucleotide composition analyses showed little heterogeneity among the four geometrid subfamilies involved herein, and overall, nad6 and atp8 have higher nucleotide diversity and Ka/Ks rate in Geometridae. In addition, the taxonomic assignments of the nine species, historically defined by morphological studies, were confirmed by various phylogenetic analyses based on the hitherto most extensive mitogenomic sampling in Geometroidea.

Memory and processing speed impairments in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Cognitive impairment, an intrinsic feature of major depressive disorder (MDD), affects daily and social functioning in depression patients. However, the cognitive impairment profile in MDD remains ambiguous because of the high heterogeneity of previous studies. METHODS: Four cognitive domains, including memory, processing speed, executive function (EF), and attention, were assessed in 184 first-episode drug-naïve (FEDN) MDD patients and matched 71 healthy controls (HCs). The effects of demographic and depressive factors on cognitive performance were analyzed using various statistical methods, including multi-factor analysis of variance, Mann-Whitney U test, and Spearman's rank correlation. In addition, the impact of depression severity on cognitive function was further assessed using subgroup analyses and partial correlation analyses. RESULTS: Age and education significantly impacted most cognitive performances, and depression severity appeared to influence processing speed. Moreover, cognitive scores in memory and processing speed, rather than in EF and attention, were significantly different between FEDN MDD patients and HCs after controlling for sex, age, educational attainment, household income, and body mass index. LIMITATIONS: The number of HCs was relatively small, which may have slightly reduced the study's statistical power. CONCLUSIONS: Age and educational attainment have confirmative confounding effects greater than those of depression in most cognitive functions. More importantly, memory and processing speed were impaired in MDD after strictly controlling for confounders. These findings provide new information for understanding the pattern of cognitive impairment and offer clues for further exploring the pathogenesis of cognitive abnormalities in MDD.

Exploring the Mechanism of Realgar against Esophageal Cancer Based on Ferroptosis Induced by ROS-ASK1-p38 MAPK Signaling Pathway.

Background: Realgar (REA), a Chinese herbal decoction, has been used to treat various tumors and has produced positive outcomes; however, there is a lack of convincing evidence for the treatment of esophageal cancer. The present study aimed to investigate the effects of REA on esophageal cancer (EC) and explore its mechanism. Methods: EC cells Eca109 and KYSE150 were selected for this study, and different groups of treated cells were set up. We studied the inhibition rate and half inhibition concentration (IC50) by CCK-8 method, the clone formation assay was used to detect the clone formation ability, the scratch assay is used to determine the cell migration ability, the Transwell assay was used to detect the cell invasion ability, the protein expressions of E-cadherin, Slug, N-cadherin, ASK1, p38 MAPK, p-p38 MAPK, and GPX4 were determined using Western blot, the mRNA expressions of ASK1 and p38 MAPK were assessed using qRT-PCR, transmission electron microscopy was used to observe the cellular ultrastructure, Prussian blue staining was used to observe the intracellular iron particle distribution, and biochemical analysis of cellular MDA, SOD, GSH, and GPXS activities, flow cytometric analysis of cellular ROS levels, immunofluorescence staining to detect cellular GPX4 expression, and JC-1 method to detect mitochondrial membrane potential were used. Results: REA inhibited the proliferation of Eca109 and KYSE150 cells in a time- and concentration-dependent manner, and REA significantly inhibited the migration and invasion of Eca109 and KYSE150 cells and activated the cellular ferroptosis and ROS-ASK1-p38 MAPK signaling pathways (P < 0.05). Inhibition of activation of the ROS-ASK1-p38 MAPK signaling pathway promoted the inhibition of proliferation, migration, and invasion of Eca109 and KYSE150 cells and the induction of ferroptosis by REA. Conclusion: REA induced ferroptosis and inhibited the migration of EC cells by activating the ROS-ASK1-p38 MAPK signaling pathway.

Neferine alleviates chronic stress-induced depression by regulating monoamine neurotransmitter secretion and gut microbiota structure.

Neferine (Nef) might possess anti-depressive properties; however, its therapeutic effects are yet to be elucidated. Therefore, in this study, we aimed to explore the anti-depressant property of Nef using a mouse model of chronic stress-induced depression. Fifteen depression-prone mice were randomly selected and divided into three groups, namely, the model, Nef, and fluoxetine (Flu) groups. We observed that in tail suspension and forced swimming tests, the Nef and Flu treatments significantly decreased the immobility time of the depressed mice, and increased their sucrose preference indices. Moreover, both Nef and Flu treatments induced significant increases in the levels of anti-depressant neurotransmitters, including dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and also reduced pathological damage to the hippocampus of the depressed mice. Incidentally, Illumina MiSeq sequencing analysis demonstrated that the relative abundance of Lactobacillus in the intestinal microbiota of depressed mice was restored after Nef/Flu treatment. Moreover, colonic Lactobacillus abundance was positively correlated with the levels of DA, 5-HT, and NE in the hippocampus of the mice. In conclusion, Nef improved monoamine neurotransmitter secretion and modulated the intestinal flora structure, particularly the abundance of Lactobacillus. Hence, it showed considerable anti-depressant potential, and might be a prospective anti-depressant therapeutic agent.

Gut microbiome: A potential indicator for predicting treatment outcomes in major depressive disorder.

The therapeutic outcomes in major depressive disorder (MDD), one of the most common and heterogeneous mental illnesses, are affected by factors that remain unclear and often yield unsatisfactory results. Herein, we characterized the composition and metabolic function of the gut microbiota of patients with MDD during antidepressant treatment, based on 16S rRNA sequencing and metabolomics. The microbial signatures at baseline differed significantly between responder and non-responder groups. The gut microbiota of the non-responder group was mainly characterized by increased relative abundances of the phylum Actinobacteria, families Christensenellaceae and Eggerthellaceae, and genera Adlercreutzia and Christensenellaceae R7 group compared to that of the responder group. Additionally, the gut microbiota composition of the responder and non-responder groups differed significantly before and after treatment, especially at the genus level. Moreover, 20 differential metabolites between the responder and non-responder groups were identified that were mainly involved in lipid metabolism (cholestane steroids and steroid esters). Eggerthellaceae and Adlercreutzia displayed strong co-occurrence relationships with certain metabolites, suggesting alternations in the gut microbiome, and associated metabolites may be potential mediators of successful antidepressant treatment. Overall, our study demonstrates that alterations in gut microbiota composition and metabolic function might be relevant to the response to antidepressants, thereby providing insight into mechanisms responsible for their efficacy.

Nine Mitochondrial Genomes of the Pyraloidea and Their Phylogenetic Implications (Lepidoptera).

The Pyraloidea is one of the species-rich superfamilies of Lepidoptera and contains numerous economically important pest species that cause great loss in crop production. Here, we sequenced and annotated nine complete mitogenomes for Pyraloidea, and further performed various phylogenetic analyses, to improve our understanding of mitogenomic evolution and phylogeny of this superfamily. The nine mitogenomes were circular, double-stranded molecules, with the lengths ranging from 15,214 bp to 15,422 bp, which are comparable to other reported pyraloid mitogenomes in size. Gene content and arrangement were highly conserved and are typical of Lepidoptera. Based on the hitherto most extensive mitogenomic sampling, our various resulting trees showed generally congruent topologies among pyraloid subfamilies, which are almost in accordance with previous multilocus studies, indicating the suitability of mitogenomes in inferring high-level relationships of Pyraloidea. However, nodes linking subfamilies in the "non-PS clade" were not completely resolved in terms of unstable topologies or low supports, and future investigations are needed with increased taxon sampling and molecular data. Unexpectedly, Orybina Snellen, represented in a molecular phylogenetic investigation for the first time, was robustly placed as basal to the remaining Pyralidae taxa across our analyses, rather than nested in Pyralinae of Pyralidae as morphologically defined. This novel finding highlights the need to reevaluate Orybina monophyly and its phylogenetic position by incorporating additional molecular and morphological evidence.

Distributed parallel computing in stochastic modeling of groundwater systems.

Stochastic modeling is a rapidly evolving, popular approach to the study of the uncertainty and heterogeneity of groundwater systems. However, the use of Monte Carlo-type simulations to solve practical groundwater problems often encounters computational bottlenecks that hinder the acquisition of meaningful results. To improve the computational efficiency, a system that combines stochastic model generation with MODFLOW-related programs and distributed parallel processing is investigated. The distributed computing framework, called the Java Parallel Processing Framework, is integrated into the system to allow the batch processing of stochastic models in distributed and parallel systems. As an example, the system is applied to the stochastic delineation of well capture zones in the Pinggu Basin in Beijing. Through the use of 50 processing threads on a cluster with 10 multicore nodes, the execution times of 500 realizations are reduced to 3% compared with those of a serial execution. Through this application, the system demonstrates its potential in solving difficult computational problems in practical stochastic modeling.

(Z)-3-[(4-Eth-oxy-phen-yl)(hy-droxy)methyl-idene]-1-isopropyl-pyrrolidine-2,4-dione.

In the title compound, C(16)H(19)NO(4), a potent new herbicide, the dihedral angle between the benzene and pyrrolidine rings is 11.09 (8)°. Intra-molecular O-H⋯O and C-H⋯O hydrogen bonds are observed.

(4Z)-4-[(Cyclo-propyl-amino)(phen-yl)methyl-ene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

In the title compound, C(20)H(19)N(3)O, the dihedral angles formed by the pyrazolone ring with the two phenyl rings are 64.27 (6) and 17.00 (6)°. The mol-ecular structure is stabilized by intra-molecular N-H⋯O and C-H⋯O hydrogen bonds. In the crystal, the mol-ecules are linked into chains along the b axis by inter-molecular C-H⋯O hydrogen bonds.

4-[(Z)-Allyl-amino-(phen-yl)methyl-ene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

The title compound, C(20)H(19)N(3)O, exists in a keto-enamine tautomeric form. The pyrazolone ring makes dihedral angles of 20.52 (10) and 77.73 (5)° with the two phenyl rings and an intra-molecular N-H⋯O hydrogen bond occurs. A weak inter-molecular C-H⋯O hydrogen bond is observed in the crystal structure. The allyl group is disordered over two positions, with site-occupancy factors of 0.533 (5) and 0.467 (5).

1-sec-Butyl-3-[hy-droxy(1-methyl-1H-indol-3-yl)methyl-idene]pyrrolidine-2,4-dione.

In the title compound, C(18)H(20)N(2)O(3), the dihedral angle between the indole ring system (r.m.s. deviation = 0.018 Å) and the hy-droxy-methyl-enepyrrolidine-2,4-dione plane (r.m.s. deviation = 0.036 Å) is 9.87 (7)°. The keto and enol groups are involved in an intra-molecular O-H⋯O hydrogen bond. An intra-molecular C-H⋯O inter-action also occurs. The sec-butyl group is disordered over two orientations corresponding to an approximate 180° rotation about the N-C bond, with occupancies of 0.670 (6) and 0.330 (6). In the crystal, mol-ecules are linked into chains along the c axis by C-H⋯O hydrogen bonds.

[Tongxie Yaofang inhibits the contraction of colonic smooth muscle isolated from rats through a mechanism related to calcium mobilization].

OBJECTIVE: To study the relationship between the inhibitory effects of Tongxie Yaofang, a compound traditional Chinese herbal medicine, on the contraction of the colonic smooth muscle isolated from rats and calcium mobilization. METHODS: By measuring the tension of the isolated colonic smooth muscle strips, the inhibitory effects of Tongxie Yaofang on the contraction induced by acetylcholine (ACh), KCl and exhausting Ca(2+) of internal calcium store were assessed respectively. RESULTS: Tongxie Yaofang could concentration-dependently inhibit the contraction of isolated rat colonic smooth muscle strips induced by KCl and exhausting the Ca(2+) of internal calcium store. Tongxie Yaofang could also inhibit the tension of the second contractile phase induced by ACh (P<0.01, vs control), but had no influence on the first contractile phase. CONCLUSION: Tongxie Yaofang can inhibit the contraction of isolated rat colonic smooth muscle strips mainly by preventing the influx of extracellular Ca(2+), which may be associated with blocking voltage-dependent channel, store-operated channel and receptor-operated channel, but not by preventing the release of internal Ca(2+) from calcium store.

4-{(Z)-(sec-Butyl-amino)(phen-yl)methyl-ene}-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

In the title compound, C(21)H(23)N(3)O, the dihedral angles formed by the pyrazolone ring with two phenyl rings are 10.38 (8) and 76.94 (6)°. The sec-butyl-amino group is disordered over two positions, with refined site-occupancy factors of 0.730 (4) and 0.270 (4). The compound could potentially be ligand stabilized in the solid state in a keto-enamine tautomeric form. The amine functionality is involved in an intra-molecular N-H⋯O hydrogen bond, while weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds participate in the formation of the crystal structure.

catena-Poly[[diaqua-(1,2,3-benzothia-diazole-7-carboxyl-ato-κO)copper(II)]-µ-1,2,3-benzothia-diazole-7-carboxyl-ato-κN:O].

In the polymeric title complex, [Cu(C(7)H(3)N(2)O(2)S)(2)(H(2)O)(2)](n), the Cu(II) centre is surrounded by three 1,2,3-benzothia-diazole-7-carboxyl-ate and two water mol-ecules. A 1,2,3-benzothia-diazole-7-carboxyl-ate ligand bridges two Cu(II) centres, with a Cu⋯Cu distance of 9.006 (2) Å. The four O atoms in the equatorial planes around each Cu(II) centre form a distorted square-planar arrangement, while the distorted square-pyramidal coordination is completed by the symmetry-related N atoms of the bridging 1,2,3-benzothia-diazole-7-carboxyl-ate ligands. In the crystal structure, inter-molecular O-H⋯O and O-H⋯N hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular network.

(4Z)-4-[(4-Methoxy-benzyl-amino)(phen-yl)methyl-ene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

In the title compound, C(25)H(23)N(3)O(2), the dihedral angles formed by the pyrazolone ring with the three aromatic rings are 14.59 (7), 79.35 (5) and 87.10 (6)°. Three intra-molecular C-H⋯O, C-H⋯N and N-H⋯O hydrogen-bond inter-actions are present. The crystal structure is stabilized by two weak inter-molecular C-H⋯O and C-H⋯N hydrogen-bond inter-actions.

3-[(Hydr-oxy)(4-isoprop-oxy-2-methoxy-phen-yl)methyl-ene]-1-isopropyl-pyrrol-idine-2,4-dione.

The title compound, C(18)H(23)NO(5), a potential herbicide, has an enol group that is intra-molecularly hydrogen bonded to a keto O atom. The dihedral angle between the six-membered ring formed by the enol group and the aromatic benzene ring is 53.35 (6)°.