Nucleus accumbens deep brain stimulation improves depressive-like behaviors through BDNF-mediated alterations in brain functional connectivity of dopaminergic pathway.

Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased pAMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD.

Major Facilitator Superfamily Transporter Participates in the Formation of Dimeric Sorbicillinoids Pigments.

Understanding the biosynthetic pathways of fungal pigments can help elucidate their roles in fungal growth processes. Trichodimerol is a unique cage-like dimeric sorbicillinoids pigment that is commonly isolated from many fungi, however, its biosynthesis is just partially clarified. In this study, we report that a biosynthetic gene cluster encoded major facilitator superfamily transporter (StaE) from the fungus Stagonospora sp. SYSU-MS7888 is involved in the formation of trichodimerol, together with several other dimeric sorbicillinoids. Using Aspergillus oryzae NSARI as a heterologous host, we demonstrated that the formation of dimeric sorbicillinoids required co-expression of the transporter StaE with biosynthetic genes (two PKSs and one monooxygenase) that are responsible for constructing the monomer precursor sorbicillinol. Fluorescence microscopy results showed that eGFP-tagged StaE is localized on the endoplasmic reticulum, suggesting that sorbicillinoid dimerizations might be compartmentalized in this organelle.

Virome Analysis Provides an Insight into the Viral Community of Chinese Mitten Crab Eriocheir sinensis.

Recent advances in viromics have led to the discovery of a great diversity of RNA viruses and the identification of a large number of viral pathogens. A systematic exploration of viruses in Chinese mitten crab (Eriocheir sinensis), one of the most important aquatic commercial species, is still lacking. Here, we characterized the RNA viromes of asymptomatic, milky disease (MD)-affected, and hepatopancreatic necrosis syndrome (HPNS)-affected Chinese mitten crabs collected from 3 regions in China. In total, we identified 31 RNA viruses belonging to 11 orders, 22 of which were first reported here. By comparing viral composition between samples, we observed high variation in viral communities across regions, with most of the viral species being region-specific. We proposed to establish several novel viral families or genera based on the phylogenetic relationships and genome structures of viruses discovered in this study, expanding our knowledge of viral diversity in brachyuran crustaceans. IMPORTANCE High-throughput sequencing and meta-transcriptomic analysis provide us with an efficient tool to discover unknown viruses and explore the composition of viral communities in specific species. In this study, we investigated viromes in asymptomatic and diseased Chinese mitten crabs collected from three distant locations. We observed high regional variation in the composition of viral species, highlighting the importance of multi-location sampling. In addition, we classified several novel and ICTV-unclassified viruses based on their genome structures and phylogenetic relationships, providing a new perspective on current viral taxa.

Evolutionary ecology of microbial populations inhabiting deep sea sediments associated with cold seeps.

Deep sea cold seep sediments host abundant and diverse microbial populations that significantly influence biogeochemical cycles. While numerous studies have revealed their community structure and functional capabilities, little is known about genetic heterogeneity within species. Here, we examine intraspecies diversity patterns of 39 abundant species identified in sediment layers down to 430 cm below the sea floor across six cold seep sites. These populations are grouped as aerobic methane-oxidizing bacteria, anaerobic methanotrophic archaea and sulfate-reducing bacteria. Different evolutionary trajectories are observed at the genomic level among these physiologically and phylogenetically diverse populations, with generally low rates of homologous recombination and strong purifying selection. Functional genes related to methane (pmoA and mcrA) and sulfate (dsrA) metabolisms are under strong purifying selection in most species investigated. These genes differ in evolutionary trajectories across phylogenetic clades but are functionally conserved across sites. Intrapopulation diversification of genomes and their mcrA and dsrA genes is depth-dependent and subject to different selection pressure throughout the sediment column redox zones at different sites. These results highlight the interplay between ecological processes and the evolution of key bacteria and archaea in deep sea cold seep extreme environments, shedding light on microbial adaptation in the subseafloor biosphere.

The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment.

BACKGROUND: Vestimentifera (Polychaeta, Siboglinidae) is a taxon of deep-sea worm-like animals living in deep-sea hydrothermal vents, cold seeps, and organic falls. The morphology and lifespan of Ridgeia piscesae, which is the only vestimentiferan tubeworm species found in the hydrothermal vents on the Juan de Fuca Ridge, vary greatly according to endemic environment. Recent analyses have revealed the genomic basis of adaptation in three vent- and seep-dwelling vestimentiferan tubeworms. However, the evolutionary history and mechanism of adaptation in R. piscesae, a unique species in the family Siboglinidae, remain to be investigated. RESULT: We assembled a draft genome of R. piscesae collected at the Cathedral vent of the Juan de Fuca Ridge. Comparative genomic analysis showed that vent-dwelling tubeworms with a higher growth rate had smaller genome sizes than seep-dwelling tubeworms that grew much slower. A strong positive correlation between repeat content and genome size but not intron size and the number of protein-coding genes was identified in these deep-sea tubeworm species. Evolutionary analysis revealed that Ridgeia pachyptila and R. piscesae, the two tubeworm species that are endemic to hydrothermal vents of the eastern Pacific, started to diverge between 28.5 and 35 million years ago. Four genes involved in cell proliferation were found to be subject to positive selection in the genome of R. piscesae. CONCLUSION: Ridgeia pachyptila and R. piscesae started to diverge after the formation of the Gorda/Juan de Fuca/Explorer ridge systems and the East Pacific Rise. The high growth rates of vent-dwelling tubeworms might be derived from their small genome sizes. Cell proliferation is important for regulating the growth rate in R. piscesae.

Long-read genome assemblies reveal a cis-regulatory landscape associated with phenotypic divergence in two sister Siniperca fish species.

Due to the difficulty in accurately identifying structural variants (SVs) across genomes, their impact on cis-regulatory divergence of closely related species, especially fish, remains to be explored. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remains poorly understood. Siniperca chuatsi and S. scherzeri are closely related but divergent in several phenotypic traits, making them an ideal model to study cis-regulatory evolution in sister species. Here, we generated chromosome-level genomes of S. chuatsi and S. scherzeri, with assembled genome sizes of 716.35 and 740.54 Mb, respectively. The evolutionary histories of S. chuatsi and S. scherzeri were studied by inferring dynamic changes in ancestral population sizes. To explore the genetic basis of adaptation in S. chuatsi and S. scherzeri, we performed gene family expansion and contraction analysis and identified positively selected genes (PSGs). To investigate the role of SVs in cis-regulatory divergence of closely related fish species, we identified high-quality SVs as well as divergent H3K27ac and H3K4me3 domains in the genomes of S. chuatsi and S. scherzeri. Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in phenotypic divergence between S. chuatsi and S. scherzeri. Additionally, divergent broad H3K4me3 domains were mostly associated with cancer-related genes in S. chuatsi and S. scherzeri and contributed to their phenotypic divergence.

Temporal offset association between the number of irinotecan-related adverse reactions and pharmacogenomic studies: A cross-correlation analysis.

Objectives: Studies have proved that UGT1A1 (*6, *28 and *93) gene polymorphism was closely related to the side effects of irinotecan. This study intends to perform a correlation analysis on the relationship between pharmacogenomic studies and ADRs based on time series. Methods: The ADRs related to irinotecan were derived through the FAERS; searched all pharmacogenomic studies in PubMed and Web of Science; then analyzed the sequence of correlation coefficients between total ADRs, fatal ADRs and pharmacogenomic studies under different time offset. Results: There is a positive correlation between the number of total ADRs and pharmacogenomic studies, of which the maximum correlation coefficient was 0.78 (95 % CI: 0.58-0.90), with a lag of 1 year. There is also a positive correlation between the number of fatal ADRs and pharmacogenomic studies, with the maximum correlation coefficient of 0.87 (95 % CI: 0.73-0.94) and a offset of - 4 years. Conclusion: It was found that both the total ADRs and fatal ADRs were significantly positively correlated with change trend of published pharmacogenomic literatures, which confirmed the role of pharmacogenomic research in promoting the safe use of irinotecan, and have a faster response time in reducing fatal ADRs during clinical application.

UGT1A1 Genetic Testing for Irinotecan Should be done before Starting the Treatment, Rather than after the Development of Serious Adverse Drug Reactions.

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Gene fusion as an important mechanism to generate new genes in the genus Oryza.

BACKGROUND: Events of gene fusion have been reported in several organisms. However, the general role of gene fusion as part of new gene origination remains unknown. RESULTS: We conduct genome-wide interrogations of four Oryza genomes by designing and implementing novel pipelines to detect fusion genes. Based on the phylogeny of ten plant species, we detect 310 fusion genes across four Oryza species. The estimated rate of origination of fusion genes in the Oryza genus is as high as 63 fusion genes per species per million years, which is fixed at 16 fusion genes per species per million years and much higher than that in flies. By RNA sequencing analysis, we find more than 44% of the fusion genes are expressed and 90% of gene pairs show strong signals of purifying selection. Further analysis of CRISPR/Cas9 knockout lines indicates that newly formed fusion genes regulate phenotype traits including seed germination, shoot length and root length, suggesting the functional significance of these genes. CONCLUSIONS: We detect new fusion genes that may drive phenotype evolution in Oryza. This study provides novel insights into the genome evolution of Oryza.

The genome of an apodid holothuroid (Chiridota heheva) provides insights into its adaptation to a deep-sea reducing environment.

Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by lacking oxygen and photosynthesis-derived nutrients. Most animals acquire nutrition in cold seeps or hydrothermal vents by maintaining epi- or endosymbiotic relationship with chemoautotrophic microorganisms. Although several seep- and vent-dwelling animals hosting symbiotic microbes have been well-studied, the genomic basis of adaptation to deep-sea reducing environment in nonsymbiotic animals is still lacking. Here, we report a high-quality genome of Chiridota heheva Pawson & Vance, 2004, which thrives by extracting organic components from sediment detritus and suspended material, as a reference for nonsymbiotic animal's adaptation to deep-sea reducing environments. The expansion of the aerolysin-like protein family in C. heheva compared with other echinoderms might be involved in the disintegration of microbes during digestion. Moreover, several hypoxia-related genes (Pyruvate Kinase M2, PKM2; Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase, LHPP; Poly(A)-specific Ribonuclease Subunit PAN2, PAN2; and Ribosomal RNA Processing 9, RRP9) were subject to positive selection in the genome of C. heheva, which contributes to their adaptation to hypoxic environments.

Environmental risk characteristics of bacterial antibiotic resistome in Antarctic krill.

Antibiotic resistance genes (ARGs) are ubiquitous in nature, especially in the current era of antibiotic abuse, and their existence is a global concern. In the present study, we discovered that Antarctic krill-related culturable bacteria are resistant to ß-lactam, tetracyclines, aminoglycosides, and sulphamethoxazole/trimethoprim based on the antibiotic efflux mechanism. In addition, the co-occurrence of ARGs with insertion sequence (IS) (tnpA, IS91) and Intl1 on the isolates and the phylogenetic analysis results of the whole-genome revealed low-frequency ARG transfer events, implying the transferability of these ARGs. These findings provide an early warning for the wide assessment of Antarctic microbiota in the spread of ARGs. Our work provides novel insights into understanding ARGs in culturable host-associated microorganisms, and their ecological risks and has important implications for future risk assessments of antibiotic resistance in extreme environments.

A convenient polyculture system that controls a shrimp viral disease with a high transmission rate.

Developing ecological approaches for disease control is critical for future sustainable aquaculture development. White spot syndrome (WSS), caused by white spot syndrome virus (WSSV), is the most severe disease in cultured shrimp production. Culturing specific pathogen-free (SPF) broodstock is an effective and widely used strategy for controlling WSS. However, most small-scale farmers, who predominate shrimp aquaculture in developing countries, cannot cultivate SPF shrimp, as they do not have the required infrastructure and skills. Thus, these producers are more vulnerable to WSS outbreaks than industrial farms. Here we developed a shrimp polyculture system that prevents WSS outbreaks by introducing specific fish species. The system is easy to implement and requires no special biosecurity measures. The promotion of this system in China demonstrated that it allowed small-scale farmers to improve their livelihood through shrimp cultivation by controlling WSS outbreaks and increasing the production of ponds.

Distinct Expression and Methylation Patterns for Genes with Different Fates following a Single Whole-Genome Duplication in Flowering Plants.

For most sequenced flowering plants, multiple whole-genome duplications (WGDs) are found. Duplicated genes following WGD often have different fates that can quickly disappear again, be retained for long(er) periods, or subsequently undergo small-scale duplications. However, how different expression, epigenetic regulation, and functional constraints are associated with these different gene fates following a WGD still requires further investigation due to successive WGDs in angiosperms complicating the gene trajectories. In this study, we investigate lotus (Nelumbo nucifera), an angiosperm with a single WGD during the K-pg boundary. Based on improved intraspecific-synteny identification by a chromosome-level assembly, transcriptome, and bisulfite sequencing, we explore not only the fundamental distinctions in genomic features, expression, and methylation patterns of genes with different fates after a WGD but also the factors that shape post-WGD expression divergence and expression bias between duplicates. We found that after a WGD genes that returned to single copies show the highest levels and breadth of expression, gene body methylation, and intron numbers, whereas the long-retained duplicates exhibit the highest degrees of protein-protein interactions and protein lengths and the lowest methylation in gene flanking regions. For those long-retained duplicate pairs, the degree of expression divergence correlates with their sequence divergence, degree in protein-protein interactions, and expression level, whereas their biases in expression level reflecting subgenome dominance are associated with the bias of subgenome fractionation. Overall, our study on the paleopolyploid nature of lotus highlights the impact of different functional constraints on gene fate and duplicate divergence following a single WGD in plant.

Dummy molecularly imprinted microspheres prepared by Pickering emulsion polymerization for matrix solid-phase dispersion extraction of three azole fungicides from fish samples.

Dummy molecularly imprinted microspheres (DMIMs) were synthesized by Pickering emulsion polymerization and used as the matrix solid-phase dispersion extraction (MSPD) sorbent for sample pre-treatment of azole fungicides in fish samples. Alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol (DCE) was used as the fragment dummy template for the imprinting of climbazole (CBZ), clotrimazole (CMZ) and miconazole (MNZ). The morphology of the microspheres were characterized by scanning electron microscopy (SEM) and nitrogen adsorption measurements, narrow diameter distribution (20-50 µm) with regular spherical shape and high surface area (SBET = 408.91 ± 6.72 m2 g-1) were achieved. Good class-selectivity of the DMIMs was found for CBZ, CMZ and MNZ by static adsorption experiments. The imprinted microspheres as MSPD sorbent was then evaluated for the extraction and purification of CBZ, CMZ and MNZ in fish samples. The extracted azole fungicides were detected by HPLC-DAD analysis at 225 nm. MSPD conditions including elution, mass ratio of sample/sorbent and washing were carefully evaluated. The optimized MSPD method have good recoveries (89.2-101.5%) and reproducibility (RSDs 1.6-4.8%, n = 5) for fish samples spiked at 0.5, 2.5 and 12.5 µg g-1. The limits of detection (LODs) were 0.045, 0.036 and 0.033 µg g-1 for CBZ, CMZ and MNZ, respectively. The results show that this method has a good application prospect for the pretreatment of azole fungicides in fish samples.

Rh(III)-Catalyzed Cascade Reactions of Sulfoxonium Ylides with α-Diazocarbonyl Compounds: An Access to Highly Functionalized Naphthalenones.

An unprecedented cascade reaction of benzoyl sulfoxonium ylides with α-diazocarbonyl compounds leading to the formation of highly functionalized naphthalenones containing a ß-ketosulfoxonium ylide moiety is presented. Promisingly, the naphthalenone derivative thus obtained was found to be a versatile intermediate toward diversely functionalized naphthalene derivatives including substituted 1-naphthol, 2-hydroxynaphthalen-1(2 H)-one, naphthalen-1,2-dione, and 2-(methylsulfinyl)naphthalen-1-ol.

Rapid evolution of protein diversity by de novo origination in Oryza.

New protein-coding genes that arise de novo from non-coding DNA sequences contribute to protein diversity. However, de novo gene origination is challenging to study as it requires high-quality reference genomes for closely related species, evidence for ancestral non-coding sequences, and transcription and translation of the new genes. High-quality genomes of 13 closely related Oryza species provide unprecedented opportunities to understand de novo origination events. Here, we identify a large number of young de novo genes with discernible recent ancestral non-coding sequences and evidence of translation. Using pipelines examining the synteny relationship between genomes and reciprocal-best whole-genome alignments, we detected at least 175 de novo open reading frames in the focal species O. sativa subspecies japonica, which were all detected in RNA sequencing-based transcriptomes. Mass spectrometry-based targeted proteomics and ribosomal profiling show translational evidence for 57% of the de novo genes. In recent divergence of Oryza, an average of 51.5 de novo genes per million years were generated and retained. We observed evolutionary patterns in which excess indels and early transcription were favoured in origination with a stepwise formation of gene structure. These data reveal that de novo genes contribute to the rapid evolution of protein diversity under positive selection.

Dummy molecularly imprinted solid phase extraction of climbazole from environmental water samples.

Dummy molecularly imprinted polymer (DMIP) for climbazole (CBZ) was synthesized for the first time employing miconazole (MNZ) as the dummy template together with methacrylic acid (MAA) monomer, ethylene glycol dimethacrylate (EGDMA) cross-linker and acetonitrile (ACN) porogen. The selectivity and capacity of the prepared MNZ-DMIP was estimated for CBZ by high-performance liquid chromatography (HPLC) and equilibrium binding experiments. Imprinting factor (IF) with a value of 7.0 was achieved, much higher than the CBZ templated MIP (IF = 3.5). Heterogeneous binding sites were found in the MNZ-DMIP, the corresponding saturation capacity and dissociation constant for the high and low affinity binding sites were 6.761 µmol g-1 and 0.3027 mmol L-1, 43.60 µmol g-1 and 4.055 mmol L-1, respectively. High efficient method based on dummy molecularly imprinted solid phase extraction (DMISPE) coupled with HPLC was established for the selective enrichment of CBZ in river and tap water using MNZ-DMIP as sorbent. DMISPE conditions including sample loading pH/volume, selective washing and elution solvents were carefully optimized. The developed method showed good recoveries (82.3-96.2%) and repeatability (RSDs 0.6-4.9%, n = 5) for samples spiked at three different concentration levels (0.2, 1.0 and 5.0 µg L-1). The detection limit was determined as 0.012 µg L-1. The results demonstrated good potential of this method for sample pretreatment of CBZ in environmental water samples.

Preparation and evaluation of dummy-template molecularly imprinted polymer as a potential sorbent for solid phase extraction of imidazole fungicides from river water.

Dummy molecularly imprinted polymer (DMIP) for imidazole fungicides was prepared for the first time using alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol (DCE) as the fragment template. The imprinting selectivity of DCE-DMIP was evaluated for climbazole (CBZ), clotrimazole (CMZ) and miconazole (MNZ) by liquid chromatography, imprinting factors of 10.9, 10.8 and >10.7 were achieved, respectively. Heterogeneous binding sites were found in the DCE-DMIP, the corresponding saturation capacity and dissociation constant for the high affinity binding sites were 13.05 µmol g-1 and 0.4701 mmol L-1. High efficient method based on dummy molecularly imprinted solid phase extraction (DMISPE) coupled with HPLC was established for the selective enrichment of CBZ, CMZ and MNZ in river water using DCE-DMIP as sorbent. DMISPE conditions including sample loading pH/volume, selective washing and elution solvents were carefully optimized. The developed method showed good recoveries (84.2-95.0%) and precision (RSDs 1.7-5.0%, n = 5) for samples spiked at two different concentration levels (0.5 and 2.5 µg L-1). The detection limits were ranged from 0.023 to 0.031 µg L-1. The results demonstrated good potential of this method for sample pretreatment of azole fungicides in environmental water samples.

Publisher Correction: Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genus Oryza.

This article was not made open access when initially published online, which was corrected before print publication. In addition, ORCID links were missing for 12 authors and have been added to the HTML and PDF versions of the article.