An integrated QTL mapping and transcriptome sequencing provides further molecular insights and candidate genes for stem strength in rapeseed (Brassica napus L.).

KEY MESSAGE: We detected the major QTL- qSR.A07, which regulated stem strength and was fine-mapped to 490 kb. BnaA07G0302800ZS and BnaA07G0305700ZS as the candidate functional genes were identified at qSR.A07 locus. The stem's mechanical properties reflect its ability to resist lodging. In rapeseed (Brassica napus L.), although stem lodging negatively affects yield and generates harvesting difficulties, the molecular regulation of stem strength remains elusive. Hence, this study aimed to unravel the main loci and molecular mechanisms governing rapeseed stem strength. A mapping population consisting of 267 RILs (recombinant inbred lines) was developed from the crossed between ZS11 (high stem strength) and 4D122 (low stem strength), and two mechanical properties of stems including stem breaking strength and stem rind penetrometer resistance were phenotyped in four different environments. Four pleiotropic QTLs that were stable in at least two environments were detected. qSR.A07, the major one, was fine-mapped to a 490 kb interval between markers SA7-2711 and SA7-2760 on chromosome 7. It displayed epistatic interaction with qRPR.A09-2. Comparative transcriptome sequencing and analysis unveiled methionine/S-adenosylmethionine cycle (Met/SAM cycle), cytoskeleton organization, sulfur metabolism and phenylpropanoid biosynthesis as the main pathways associated with high stem strength. Further, we identified two candidate genes, BnaA07G0302800ZS and BnaA07G0305700ZS, at qSR.A07 locus. Gene sequence alignment identified a number of InDels, SNPs and amino acid variants in sequences of these genes between ZS11 and 4D122. Finally, based on these genetic variants, we developed three SNP markers of these genes to facilitate future genetic selection and functional studies. These findings offer important genetic resources for the molecular-assisted breeding of novel rapeseed stem lodging-resistant varieties.

Suppression of innate and acquired immunity in severe hand foot and mouth disease caused by EV71 infections in children.

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role. Transcriptomes of peripheral blood mononuclear cells from EV71-infected patients (n = 45) and healthy controls (n = 36) were examined. Immune pathways were up-regulated in patients with mild disease symptoms (n = 11, M) compared to the healthy controls (n = 36, H), demonstrating an effective anti-viral response upon EV71 infection. However, in patients with severe symptoms (n = 23, S) as well as severe patients following treatment (n = 11, A), their innate and acquired immune pathways were down-regulated, indicating a global immunity suppression. Such immune suppression characteristics could thus provide an opportunity for early EV-71 infection prognosis prediction. Based on our cohort, an SVM model using RNA-seq expression levels of five genes (MCL1, ZBTB37, PLEKHM1P, IFNAR2 and YEATS2) was developed and achieved a high ROC-AUC (91·3%) in predicting severe HFMD. Meanwhile, qPCR fold-changes method was performed based three genes (MCL1, IFNAR2 and YEATS2) on additional cohort. This qPCR method achieved a ROC-AUC of 78.6% in predicting severe HFMD, which the patients could be distinguished in 2-3 h. Therefore, our models demonstrate the possibility of HFMD severity prediction based on the selected biomarkers that predict severe HFMD effectively.

A systematic dissection in oilseed rape provides insights into the genetic architecture and molecular mechanism of yield heterosis.

Heterosis refers to the better performance of cross progeny compared with inbred parents, and its utilization contributes greatly to agricultural production. Several hypotheses have been proposed to explain heterosis mainly including dominance, over-dominance (or pseudo-overdominance) and epistasis. However, systematic dissection and verification of these hypotheses are rarely documented. Here, comparison of heterosis level across different traits showed that the strong heterosis of composite traits (such as yield) could be attributed to the multiplicative effects of moderate heterosis of component traits, whether at the genome or locus level. Yield heterosis was regulated by a complex trait-QTL network that was characterized by obvious centre-periphery structure, hub QTL, complex up/downstream and positive/negative feedback relationships. More importantly, we showed that better-parent heterosis on yield could be produced in a cross of two near-isogenic lines by the pyramiding and complementation of two major heterotic QTL showing partial-dominance on yield components. The causal gene (BnaA9.CYP78A9) of QC14 was identified, and its heterotic effect results from the heterozygous status of a CACTA-like transposable element in its upstream regulatory region, which led to partial dominance at expression and auxin levels, thus resulting in non-additive expression of downstream responsive genes involved in cell cycle and proliferation, eventually leading to the heterosis of cell number. Taken together, the results at the phenotypic, genetic and molecular levels were highly consistent, which demonstrated that the pyramiding effect of heterotic QTL and the multiplicative effect of individual component traits could well explain substantial parts of yield heterosis in oilseed rape. These results provide in-depth insights into the genetic architecture and molecular mechanism of yield heterosis.

Lightweight SM-YOLOv5 Tomato Fruit Detection Algorithm for Plant Factory.

Due to their rapid development and wide application in modern agriculture, robots, mobile terminals, and intelligent devices have become vital technologies and fundamental research topics for the development of intelligent and precision agriculture. Accurate and efficient target detection technology is required for mobile inspection terminals, picking robots, and intelligent sorting equipment in tomato production and management in plant factories. However, due to the limitations of computer power, storage capacity, and the complexity of the plant factory (PF) environment, the precision of small-target detection for tomatoes in real-world applications is inadequate. Therefore, we propose an improved Small MobileNet YOLOv5 (SM-YOLOv5) detection algorithm and model based on YOLOv5 for target detection by tomato-picking robots in plant factories. Firstly, MobileNetV3-Large was used as the backbone network to make the model structure lightweight and improve its running performance. Secondly, a small-target detection layer was added to improve the accuracy of small-target detection for tomatoes. The constructed PF tomato dataset was used for training. Compared with the YOLOv5 baseline model, the mAP of the improved SM-YOLOv5 model was increased by 1.4%, reaching 98.8%. The model size was only 6.33 MB, which was 42.48% that of YOLOv5, and it required only 7.6 GFLOPs, which was half that required by YOLOv5. The experiment showed that the improved SM-YOLOv5 model had a precision of 97.8% and a recall rate of 96.7%. The model is lightweight and has excellent detection performance, and so it can meet the real-time detection requirements of tomato-picking robots in plant factories.

New Insights into the TIFY Gene Family of Brassica napus and Its Involvement in the Regulation of Shoot Branching.

As plant-specific transcription factors, the TIFY family genes are involved in the responses to a series of biotic and abiotic stresses and the regulation of the development of multiple organs. To explore the potential roles of the TIFY gene family in shoot branching, which can shape plant architecture and finally determine seed yield, we conducted comprehensive genome-wide analyses of the TIFY gene family in Brassica napus. Here, HMMER search and BLASTp were used to identify the TIFY members. A total of 70 TIFY members were identified and divided into four subfamilies based on the conserved domains and motifs. These TIFY genes were distributed across 19 chromosomes. The predicted subcellular localizations revealed that most TIFY proteins were located in the nucleus. The tissue expression profile analyses indicated that TIFY genes were highly expressed in the stem, flower bud, and silique at the transcriptional level. High-proportioned activation of the dormant axillary buds on stems determined the branch numbers of rapeseed plants. Here, transcriptome analyses were conducted on axillary buds in four sequential developing stages, that is, dormant, temporarily dormant, being activated, and elongating (already activated). Surprisingly, the transcription of the majority of TIFY genes (65 of the 70) significantly decreased on the activation of buds. GO enrichment analysis and hormone treatments indicated that the transcription of TIFY family genes can be strongly induced by jasmonic acid, implying that the TIFY family genes may be involved in the regulation of jasmonic acid-mediated branch development. These results shed light on the roles of TIFY family genes in plant architecture.

Discovery of Genomic Regions and Candidate Genes Controlling Root Development Using a Recombinant Inbred Line Population in Rapeseed (Brassica napus L.).

Marker-assisted selection enables breeders to quickly select excellent root architectural variations, which play an essential role in plant productivity. Here, ten root-related and shoot biomass traits of a new F6 recombinant inbred line (RIL) population were investigated under hydroponics and resulted in high heritabilities from 0.61 to 0.83. A high-density linkage map of the RIL population was constructed using a Brassica napus 50k Illumina single nucleotide polymorphism (SNP) array. A total of 86 quantitative trait loci (QTLs) explaining 4.16-14.1% of the phenotypic variances were detected and integrated into eight stable QTL clusters, which were repeatedly detected in different experiments. The codominant markers were developed to be tightly linked with three major QTL clusters, qcA09-2, qcC08-2, and qcC08-3, which controlled both root-related and shoot biomass traits and had phenotypic contributions greater than 10%. Among these, qcA09-2, renamed RT.A09, was further fine-mapped to a 129-kb interval with 19 annotated genes in the B. napus reference genome. By integrating the results of real-time PCR and comparative sequencing, five genes with expression differences and/or amino acid differences were identified as important candidate genes for RT.A09. Our findings laid the foundation for revealing the molecular mechanism of root development and developed valuable markers for root genetic improvement in rapeseed.

Deciphering the Genetic Basis of Root and Biomass Traits in Rapeseed (Brassica napus L.) through the Integration of GWAS and RNA-Seq under Nitrogen Stress.

An excellent root system is responsible for crops with high nitrogen-use efficiency (NUE). The current study evaluated the natural variations in 13 root- and biomass-related traits under a low nitrogen (LN) treatment in a rapeseed association panel. The studied traits exhibited significant phenotypic differences with heritabilities ranging from 0.53 to 0.66, and most of the traits showed significant correlations with each other. The genome-wide association study (GWAS) found 51 significant and 30 suggestive trait-SNP associations that integrated into 14 valid quantitative trait loci (QTL) clusters and explained 5.7-21.2% phenotypic variance. In addition, RNA sequencing was performed at two time points to examine the differential expression of genes (DEGs) between high and low NUE lines. In total, 245, 540, and 399 DEGs were identified as LN stress-specific, high nitrogen (HN) condition-specific, and HNLN common DEGs, respectively. An integrated analysis of GWAS, weighted gene co-expression network, and DEGs revealed 16 genes involved in rapeseed root development under LN stress. Previous studies have reported that the homologs of seven out of sixteen potential genes control root growth and NUE. These findings revealed the genetic basis underlying nitrogen stress and provided worthwhile SNPs/genes information for the genetic improvement of NUE in rapeseed.

BnERF114.A1, a Rapeseed Gene Encoding APETALA2/ETHYLENE RESPONSE FACTOR, Regulates Plant Architecture through Auxin Accumulation in the Apex in Arabidopsis.

Plant architecture is crucial for rapeseed breeding. Here, we demonstrate the involvement of BnERF114.A1, a transcription factor for ETHYLENE RESPONSE FACTOR (ERF), in the regulation of plant architecture in Brassica napus. BnERF114.A1 is a member of the ERF family group X-a, encoding a putative 252-amino acid (aa) protein, which harbours the AP2/ERF domain and the conserved CMX-1 motif. BnERF114.A1 is localised to the nucleus and presents transcriptional activity, with the functional region located at 142-252 aa of the C-terminus. GUS staining revealed high BnERF114.A1 expression in leaf primordia, shoot apical meristem, leaf marginal meristem, and reproductive organs. Ectopic BnERF114.A1 expression in Arabidopsis reduced plant height, increased branch and silique number per plant, and improved seed yield per plant. Furthermore, in Arabidopsis, BnERF114.A1 overexpression inhibited indole-3-acetic acid (IAA) efflux, thus promoting auxin accumulation in the apex and arresting apical dominance. Therefore, BnERF114.A1 probably plays an important role in auxin-dependent plant architecture regulation.

Intestinal microbiota has important effect on severity of hand foot and mouth disease in children.

BACKGROUND: The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD. METHODS: We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls. RESULTS: We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases. CONCLUSIONS: Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

Molecular Network for Regulation of Ovule Number in Plants.

In seed-bearing plants, the ovule ("small egg") is the organ within the gynoecium that develops into a seed after fertilization. The gynoecium located in the inner compartment of the flower turns into a fruit. The number of ovules in the ovary determines the upper limit or the potential of seed number per fruit in plants, greatly affecting the final seed yield. Ovule number is an important adaptive characteristic for plant evolution and an agronomic trait for crop improvement. Therefore, understanding the mechanism and pathways of ovule number regulation becomes a significant research aspect in plant science. This review summarizes the ovule number regulators and their regulatory mechanisms and pathways. Specially, an integrated molecular network for ovule number regulation is constructed, in which phytohormones played a central role, followed by transcription factors, enzymes, other protein and micro-RNA. Of them, AUX, BR and CK are positive regulator of ovule number, whereas GA acts negatively on it. Interestingly, many ovule number regulators have conserved functions across several plant taxa, which should be the targets of genetic improvement via breeding or gene editing. Many ovule number regulators identified to date are involved in the diverse biological process, such as ovule primordia formation, ovule initiation, patterning, and morphogenesis. The relations between ovule number and related characteristics/traits especially of gynoecium/fruit size, ovule fertility, and final seed number, as well as upcoming research questions, are also discussed. In summary, this review provides a general overview of the present finding in ovule number regulation, which represents a more comprehensive and in-depth cognition on it.

A systematic dissection of the mechanisms underlying the natural variation of silique number in rapeseed (Brassica napus L.) germplasm.

Silique number is the most important component of yield in rapeseed (Brassica napus L.). To dissect the mechanism underlying the natural variation of silique number in rapeseed germplasm, a series of studies were performed. A panel of 331 core lines was employed to genome-wide association study (GWAS), and 27 loci (including 20 novel loci) were identified. The silique number difference between the more- and fewer-silique lines can be attributed to the accumulative differences in flower number and silique setting rate. Each of them accounted for 75.2% and 24.8%, respectively. The silique number was highly associated with the total photosynthesis and biomass. Microscopic analysis showed that the difference between extremely more- and fewer-silique lines normally occurred at the amount of flower bud but not morphology. Transcriptome analysis of shoot apical meristem (SAM) suggested that most of enriched groups were associated with the auxin biosynthesis/metabolism, vegetative growth and nutrition/energy accumulation. By integrating GWAS and RNA-seq results, six promising candidate genes were identified, and some of them were related to biomass accumulation. In conclusion, the natural variation of silique number is largely affected by the biomass and nutrition accumulation, which essentially reflects the positive regulatory relationship between the source and sink. Our study provides a comprehensive and systematic explanation for natural variation of silique number in rapeseed, which provides a foundation for its improvement.

Genetic and signalling pathways of dry fruit size: targets for genome editing-based crop improvement.

Fruit is seed-bearing structures specific to angiosperm that form from the gynoecium after flowering. Fruit size is an important fitness character for plant evolution and an agronomical trait for crop domestication/improvement. Despite the functional and economic importance of fruit size, the underlying genes and mechanisms are poorly understood, especially for dry fruit types. Improving our understanding of the genomic basis for fruit size opens the potential to apply gene-editing technology such as CRISPR/Cas to modulate fruit size in a range of species. This review examines the genes involved in the regulation of fruit size and identifies their genetic/signalling pathways, including the phytohormones, transcription and elongation factors, ubiquitin-proteasome and microRNA pathways, G-protein and receptor kinases signalling, arabinogalactan and RNA-binding proteins. Interestingly, different plant taxa have conserved functions for various fruit size regulators, suggesting that common genome edits across species may have similar outcomes. Many fruit size regulators identified to date are pleiotropic and affect other organs such as seeds, flowers and leaves, indicating a coordinated regulation. The relationships between fruit size and fruit number/seed number per fruit/seed size, as well as future research questions, are also discussed.

Maternal control of seed weight in rapeseed (Brassica napus L.): the causal link between the size of pod (mother, source) and seed (offspring, sink).

Seed size/weight is one of the key traits related to plant domestication and crop improvement. In rapeseed (Brassica napus L.) germplasm, seed weight shows extensive variation, but its regulatory mechanism is poorly understood. To identify the key mechanism of seed weight regulation, a systematic comparative study was performed. Genetic, morphological and cytological evidence showed that seed weight was controlled by maternal genotype, through the regulation of seed size mainly via cell number. The physiological evidence indicated that differences in the pod length might result in differences in pod wall photosynthetic area, carbohydrates and the final seed weight. We also identified two pleiotropic major quantitative trait loci that acted indirectly on seed weight via their effects on pod length. RNA-seq results showed that genes related to pod development and hormones were significantly differentially expressed in the pod wall; genes related to development, cell division, nutrient reservoir and ribosomal proteins were all up-regulated in the seeds of the large-seed pool. Finally, we proposed a potential seed weight regulatory mechanism that is specific to rapeseed and novel in plants. The results demonstrate a causal link between the size of the pod (mother, source) and the seed (offspring, sink) in rapeseed, which provides novel insight into the maternal control of seed weight and will open a new research field in plants.

Temporal genetic patterns of root growth in Brassica napus L. revealed by a low-cost, high-efficiency hydroponic system.

KEY MESSAGE: Application of a low-cost and high-efficiency hydroponic system in a rapeseed population verified two types of genetic factors ("persistent" and "stage-specific") that control root development. The root system is a vital plant component for nutrient and water acquisition and is targeted to enhance plant productivity. Genetic dissection of the root system generally focuses on a single stage, but roots grow continuously during plant development. To reveal the temporal genetic patterns of root development, we measured nine root-related traits in a rapeseed recombinant inbred line population at six continuous stages during vegetative growth, using a modified hydroponic system with low-cost and high-efficiency features that could synchronize plant growth under controlled conditions. Phenotypic correlation and growth dynamic analysis suggested the existence of two types of genetic factors ("persistent" and "stage-specific") that control root development. Dynamic (unconditional and conditional) quantitative trait loci (QTL) mapping detected 28 stage-specific and 23 persistent QTLs related to root growth. Among them, 13 early stage-specific, 19 persistent and 8 later stage-specific QTLs were detected at 7 DAS (days after sowing), 16 DAS and 5 EL (expanding leaf stage), respectively, providing efficient and adaptable stages for QTL identification. The effective prediction of biomass accumulation using root morphological traits (up to 96.6% or 92.64% at a specific stage or the final stage, respectively) verified that root growth allocation with maximum root uptake area facilitated biomass accumulation. Furthermore, marker-assistant selection, which combined the "persistent" and "stage-specific" QTLs, proved their effectiveness for root improvement with an excellent uptake area. Our results highlight the potential of high-throughput and precise phenotyping to assess the dynamic genetics of root growth and provide new insights into ideotype root system-based biomass breeding.

The high-quality genome of Brassica napus cultivar 'ZS11' reveals the introgression history in semi-winter morphotype.

Allotetraploid oilseed rape (Brassica napus L.) is an agriculturally important crop. Cultivation and breeding of B. napus by humans has resulted in numerous genetically diverse morphotypes with optimized agronomic traits and ecophysiological adaptation. To further understand the genetic basis of diversification and adaptation, we report a draft genome of an Asian semi-winter oilseed rape cultivar 'ZS11' and its comprehensive genomic comparison with the genomes of the winter-type cultivar 'Darmor-bzh' as well as two progenitors. The integrated BAC-to-BAC and whole-genome shotgun sequencing strategies were effective in the assembly of repetitive regions (especially young long terminal repeats) and resulted in a high-quality genome assembly of B. napus 'ZS11'. Within a short evolutionary period (~6700 years ago), semi-winter-type 'ZS11' and the winter-type 'Darmor-bzh' maintained highly genomic collinearity. Even so, certain genetic differences were also detected in two morphotypes. Relative to 'Darmor-bzh', both two subgenomes of 'ZS11' are closely related to its progenitors, and the 'ZS11' genome harbored several specific segmental homoeologous exchanges (HEs). Furthermore, the semi-winter-type 'ZS11' underwent potential genomic introgressions with B. rapa (Ar ). Some of these genetic differences were associated with key agronomic traits. A key gene of A03.FLC3 regulating vernalization-responsive flowering time in 'ZS11' was first experienced HE, and then underwent genomic introgression event with Ar , which potentially has led to genetic differences in controlling vernalization in the semi-winter types. Our observations improved our understanding of the genetic diversity of different B. napus morphotypes and the cultivation history of semi-winter oilseed rape in Asia.

Natural variation in ARF18 gene simultaneously affects seed weight and silique length in polyploid rapeseed.

Seed weight (SW), which is one of the three major factors influencing grain yield, has been widely accepted as a complex trait that is controlled by polygenes, particularly in polyploid crops. Brassica napus L., which is the second leading crop source for vegetable oil around the world, is a tetraploid (4×) species. In the present study, we identified a major quantitative trait locus (QTL) on chromosome A9 of rapeseed in which the genes for SW and silique length (SL) were colocated. By fine mapping and association analysis, we uncovered a 165-bp deletion in the auxin-response factor 18 (ARF18) gene associated with increased SW and SL. ARF18 encodes an auxin-response factor and shows inhibitory activity on downstream auxin genes. This 55-aa deletion prevents ARF18 from forming homodimers, in turn resulting in the loss of binding activity. Furthermore, reciprocal crossing has shown that this QTL affects SW by maternal effects. Transcription analysis has shown that ARF18 regulates cell growth in the silique wall by acting via an auxin-response pathway. Together, our results suggest that ARF18 regulates silique wall development and determines SW via maternal regulation. In addition, our study reveals the first (to our knowledge) QTL in rapeseed and may provide insights into gene cloning involving polyploid crops.

An integrated analysis of QTL mapping and RNA sequencing provides further insights and promising candidates for pod number variation in rapeseed (Brassica napus L.).

BACKGROUND: As the most important yield component in rapeseed (Brassica napus L.), pod number is determined by a series of successive growth and development processes. Pod number shows extensive variation in rapeseed natural germplasm, which is valuable for genetic improvement. However, the genetic and especially the molecular mechanism for this kind of variation are poorly understood. In this study, we conducted QTL mapping and RNA sequencing, respectively, using the BnaZNRIL population and its two parental cultivars Zhongshuang11 and No.73290 which showed significant difference in pod number, primarily due to the difference in floral organ number. RESULT: A total of eight QTLs for pod number were identified using BnaZNRIL population with a high-density SNP linkage map, each was distributed on seven linkage groups and explained 5.8-11.9% of phenotypic variance. Then, they were integrated with those previously detected in BnaZNF2 population (deriving from same parents) and resulted in 15 consensus-QTLs. Of which, seven QTLs were identical to other studies, whereas the other eight should be novel. RNA sequencing of the shoot apical meristem (SAM) at the formation stage of floral bud primordia identified 9135 genes that were differentially expressed between the two parents. Gene ontology (GO) analysis showed that the top two enriched groups were S-assimilation, providing an essential nutrient for the synthesis of diverse metabolites, and polyamine metabolism, serving as second messengers that play an essential role in flowering genes initiation. KEGG analysis showed that the top three overrepresented pathways were carbohydrate (707 genes), amino acid (390 genes) and lipid metabolisms (322 genes). In silico mapping showed that 647 DEGs were located within the confidence intervals of 15 consensus QTLs. Based on annotations of Arabidopsis homologs corresponding to DEGs, nine genes related to meristem growth and development were considered as promising candidates for six QTLs. CONCLUSION: In this study, we discovered the first repeatable major QTL for pod number in rapeseed. In addition, RNA sequencing was performed for SAM in rapeseed, which provides new insights into the determination of floral organ number. Furthermore, the integration of DEGs and QTLs identified promising candidates for further gene cloning and mechanism study.

Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression.

Serotonin-1A receptor alterations in depression: a meta-analysis of molecular imaging studies.

BACKGROUND: Postmortem studies of people who have successfully committed suicide and people with depression have implicated the serotonin-1A (5-HT1A) receptor system in the pathophysiology of depression. Several molecular imaging studies have investigated alterations in 5-HT1A receptors in patients with depression using positron emission tomography and have reported conflicting results. METHODS: We performed a meta-analysis of studies investigating the relationship between depression and 5-HT1A binding. We conducted a comprehensive search of Medline, Embase, ScienceDirect, Scopus and Springer databases for relevant studies published between January 1999 and October 2015. The meta-analysis was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. RESULTS: Ten studies were included, comprising 218 patients with depression and 261 healthy controls. The results of these studies indicated a reduction in 5-HT1A receptors in mesiotemporal cortex, yielding a summary effect estimate of -0.8 (95 % CI -1.36, -0.24). Smaller reductions were reported in 5-HT1A receptor binding in the hippocampus, raphe nuclei, insular, anterior cingulate cortex and occipital cortex of people with depression. No clear effect of depression on 5-HT1A receptors was detected in the amygdala. CONCLUSIONS: Reduced 5-HT1A receptor binding was associated with the pathology of depression and predicted altered serotonergic neurotransmission in various brain regions. These findings increase our understanding of the neurophysiological processes underlying depression.

Effect of Capsaicin-Loading Nanoparticles on Gliomas.

Capsaicin is recognized as a natural tumor preventive compound and exhibits a remarkable anticancer action. Strong inhibitory role of capsaicin on gliomas has been well documented. However, the use of capsaicin is limited due to its hydrophobicity, low affinity, and short half-life. The present study aimed to explore the physiochemical characteristics of the capsaicin-loading nanoparticles prepared by methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) amphiphilic block copolymer. It also aimed to evaluate the ability of the nanoparticles to cross the blood-brain barrier. Additionally, the uptake of nanoparticles in the glioma cells and its ability to inhibit cell proliferation were tested in human glioblastoma U251 cells. mPEG-PCL amphiphilic block copolymer was synthesized using the ring-opening polymerization method, and the capsaicin-loading nanoparticles were prepared with the solvent diffusion method. In vitro drug release assay revealed that the capsaicin-loading nanoparticles presented a slow-release characteristic. Coculture of the human glioblastoma U251 cells and the fluorescein-loading nanoparticles showed the uptake of nanoparticles in U251 cells by endocytosis. We found that the NIR-797 isothiocyanate-loading nanoparticles can cross the blood-brain barrier. In addition, the capsaicin-loading nanoparticle showed a remarkable inhibition on the growth of U251 cells. The efficacy of the capsaicin-loading nanoparticles against tumor cells was significantly superior to the capsaicin at low concentrations. It is concluded that the capsaicin-loading nanoparticles can provide an extremely promising approach for chemotherapy of gliomas.