Research Progress on the Pharmacodynamic Mechanisms of Sini Powder against Depression from the Perspective of the Central Nervous System.

Depression is a highly prevalent emotional disorder characterized by persistent low mood, diminished interest, and loss of pleasure. The pathological causes of depression are associated with neuronal atrophy, synaptic loss, and neurotransmitter activity decline in the central nervous system (CNS) resulting from injuries, such as inflammatory responses. In Traditional Chinese Medicine (TCM) theory, patients with depression often exhibit the liver qi stagnation syndrome type. Sini Powder (SNP) is a classic prescription for treating such depression-related syndrome types in China. This study systematically summarized clinical applications and experimental studies of SNP for treatments of depression. We scrutinized the active components of SNP with blood-brain barrier (BBB) permeability and speculated about the corresponding pharmacodynamic pathways relevant to depression treatment through intervening in the CNS. Therefore, this article can enhance our understanding of SNP's pharmacological mechanisms and formula construction for depression treatment. Moreover, a re-demonstration of this classic TCM prescription in the modern-science language is of great significance for future drug development and research.

The coat protein of the ilarvirus prunus necrotic ringspot virus mediates long-distance movement.

The coat protein (CP) of plant viruses generally has multiple functions involving infection, replication, movement and pathogenicity. Functions of the CP of prunus necrotic ringspot virus (PNRSV), the causal agent of several threatening diseases of Prunus fruit trees, are poorly studied. Previously, we identified a novel virus in apple, apple necrotic mosaic virus (ApNMV), which is phylogenetically related to PNRSV and probably associated with apple mosaic disease in China. Full-length cDNA clones of PNRSV and ApNMV were constructed, and both are infectious in cucumber (Cucumis sativus L.), an experimental host. PNRSV exhibited higher systemic infection efficiency with more severe symptoms than ApNMV. Reassortment analysis of genomic RNA segments 1-3 found that RNA3 of PNRSV could enhance the long-distance movement of an ApNMV chimaera in cucumber, indicating the association of RNA3 of PNRSV with viral long-distance movement. Deletion mutagenesis of the PNRSV CP showed that the basic motif from amino acids 38 to 47 was crucial for the CP to maintain the systemic movement of PNRSV. Moreover, we found that arginine residues 41, 43 and 47 codetermine viral long-distance movement. The findings demonstrate that the CP of PNRSV is required for long-distance movement in cucumber, which expands the functions of ilarvirus CPs in systemic infection. For the first time, we identified involvement of Ilarvirus CP protein during long-distance movement.

Dephenolization pyrolysis fluid improved physicochemical properties and microbial community structure of saline-alkali soils.

Saline-sodic soil is widely distributed around the world and has induced severe impacts on ecosystems and agriculture. Biomass pyrolysis fluid (BPF), as a substance rich in organic acids, has been proposed as a saline-alkali soil conditioner. One of the main problems with BPF applications is the potential contamination of the phenolic substances it contains. Therefore, the purpose of this study is to reduce the phenolic substances in BFP and study the improvement effect of BFP on saline-alkali soil. Firstly, we explored the physicochemical properties of BPF prepared at different temperatures (300 °C, 400 °C, 500 °C, 600 °C, and 700 °C). Then BPF was separated into upper phases (UP) and lower phases (LP) by a simple one-step salting-out extraction method. We found that phenolic substances were mainly concentrated in the UP (average content was 193.27 mg/g), and the content of phenolic substances in the LP was effectively reduced (average content was 64.52 mg/g). Next, we added the LP diluted at different times (0, 50, 100, 200, 400) into saline-alkali soil for improvement experiments. The experimental results show that the lower phase diluted 400 times at the pyrolysis temperature of 500℃ was added into saline-alkali soil, which greatly increased the content of soil available nutrients. Under the action of organic acids, soil pH (the average was 7.43) and total salt content could be reduced effectively, and soil enzyme activities can be increased. Microbial community analysis showed that the addition of LP could increase the proportion of Actinomycetes, which played a beneficial role in improving soil fertility and then improved the growth of Chinese cabbage.

Selection and Validation of Reference Genes for Gene Expression Studies Using Quantitative Real-Time PCR in Prunus Necrotic Ringspot Virus-Infected Cucumis sativus.

Several members of the genus Ilarvirus infect fruit trees and are distributed worldwide. Prunus necrotic ringspot virus (PNRSV) is one of the most prevalent viruses, causing significant losses. Cucumissativus can be infected by several ilarviruses, leading to obvious symptoms, including PNRSV, which suggests that cucumbers could be good hosts for the study of the pathogenesis of ilarviruses. Real-time quantitative PCR is an optimal choice for studying gene expression because of its simplicity and its fast and high sensitivity, while its accuracy is highly dependent on the stability of the reference genes. In this study, we assessed the stability of eleven reference genes with geNorm, NormFinder, ΔCt method, BestKeeper, and the ranking software, RefFinder. The results indicated that the combined use of EF1α and F-BOX was the most accurate normalization method. In addition, the host genes AGO1, AGO4, and RDR6 were selected to test the reliability of the reference genes. This study provides useful information for gene expression analysis during PNRSV infection and will facilitate gene expression studies associated with ilarvirus infection.

Detection and Simultaneous Differentiation of Three Co-infected Viruses in Zanthoxylum armatum.

Green Sichuan pepper (Zanthoxylum armatum) is an important economic fruit crop, which is widely planted in the southwest region of China. Recently, a serious disease, namely flower yellowing disease (FYD), broke out, and the virus of green Sichuan pepper nepovirus (GSPNeV) was identified to be highly correlated with the viral symptoms. Meanwhile, green Sichuan pepper idaeovirus (GSPIV) and green Sichuan pepper enamovirus (GSPEV) were also common viruses infecting green pepper. In our research, specific primers were designed according to the reported sequences of the three viruses, and a multiplex reverse transcription-polymerase chain reaction (RT-PCR) method for the simultaneous detection of GSPNeV, GSPIV, and GSPEV was established. The annealing temperature, extension time, and cycle number affecting the multiplex RT-PCR reaction were adjusted and optimized. Sensitivity analysis showed that the system could detect the three viruses simultaneously from the complementary deoxyribonucleic acid (cDNA) samples diluted by 10-3. The results of the ten samples detected by the multiplex RT-PCR system were consistent with the results of a single PCR, indicating that the method can be successfully used for rapid detection of field samples.

The GATA factor HANABA TARANU promotes runner formation by regulating axillary bud initiation and outgrowth in cultivated strawberry.

A runner, as an elongated branch, develops from the axillary bud (AXB) in the leaf axil and is crucial for the clonal propagation of cultivated strawberry (Fragaria × ananassa Duch.). Runner formation occurs in at least two steps: AXB initiation and AXB outgrowth. HANABA TARANU (HAN ) encodes a GATA transcription factor that affects AXB initiation in Arabidopsis and promotes branching in grass species, but the underlying mechanism is largely unknown. Here, the function of a strawberry HAN homolog FaHAN in runner formation was characterized. FaHAN transcripts can be detected in the leaf axils. Overexpression (OE) of FaHAN increased the number of runners, mainly by enhancing AXB outgrowth, in strawberry. The expression of the strawberry homolog of BRANCHED1 , a key inhibitor of AXB outgrowth in many plant species, was significantly downregulated in the AXBs of FaHAN -OE lines, whereas the expression of the strawberry homolog of SHOOT MERISTEMLESS, a marker gene for AXB initiation in Arabidopsis, was upregulated. Moreover, several genes of gibberellin biosynthesis and cytokinin signaling pathways were activated, whereas the auxin response pathway genes were repressed. Further assays indicated that FaHAN could be directly activated by FaNAC2, the overexpression of which in strawberry also increased the number of runners. The silencing of FaNAC2 or FaHAN inhibited AXB initiation and led to a higher proportion of dormant AXBs, confirming their roles in the control of runner formation. Taken together, our results revealed a FaNAC2-FaHAN pathway in the control of runner formation and have provided a means to enhance the vegetative propagation of cultivated strawberry.

Changes in metabolism modulate induced by viroid infection in the orchid Dendrobium officinale.

Dendrobium officinale is an important traditional Chinese medicinal herb, and the stem tissue is the main medicinal that is harvested from D. officinale. Recently, the first viroid was identified from D. officinale in China, and it has been named Dendrobium viroid (DVd). Whether DVd interferes with metabolic pathways in dendrobium plants and affects the medicinal value of the host is unknown. In this study, metabolomics data from stem tissues supported by transcriptome studies were used to investigate how metabolism modulate of D. officinale is altered by DVd infection. Our results show that metabolism of D. officinale is reprogrammed in many ways during DVd infection, and this is reflected by significant changes in the levels of flavonoids, alkaloids, and phenolic acids. Furthermore, we found that DVd infection significantly decreased the accumulation of flavonoids and alkaloid metabolites in infected stems, and the decreases in these metabolites appears to affect the medicinal components of the infected plants, weakening the host antiviral immune response as well. Conversely, phenolic acids occupy a larger proportion of the up-regulated metabolites from DVd infection in comparison with the mock-inoculated control, and the increase in the total phenolic acids may reflect the activation of the pathogen defense response in D. officinale. Taken together, our results provide an interesting overview and give a better understanding of the relationship between metabolism and DVd infection in the orchid D. officinale.

Characterization of an Isolate of Citrus Concave Gum-Associated Virus from Apples in China and Development of an RT-RPA Assay for the Rapid Detection of the Virus.

Apple (Malus domestica) fruits exhibiting bright stripe symptoms were identified in Weihai City, Shandong Province, China. To investigate the virome in the apple samples, the method of high throughput sequencing (HTS) was used to identify the viruses. It was found that the sequence of citrus concave gum-associated virus (CCGaV) was involved in the apple transcriptome dataset. The full-length genome of the CCGaV-Weihai isolate contained two segments, the RNA1 was 6674 nt in size containing a conserved RNA-dependent RNA polymerase (RdRp), and the RNA2 was ambisense, 2706 nt in length, encoding a movement protein (MP) and a coat protein (CP). Sequence alignment and phylogenetic analyses indicated that CCGaV-Weihai was more closely related to CCGaV-H2799 isolated from the apple host in the United States and distantly related to CCGaV-CGW2 from Citrus sinensis in Italy, indicating a possibly geographical and host differentiation of CCGaV isolates. This was the first identification and characterization of CCGaV infecting apples in China. Additionally, a rapid and sensitive reverse transcription recombinase polymerase amplification (RT-RPA) assay technique was established for CCGaV detection in apple plants. The RT-RPA of CCGaV was not affected by other common viruses in apple plants and is about 10-fold more sensitive than the conventional reverse transcription polymerase chain reaction method, which can be used in large-scale testing.

From the perspective of Traditional Chinese Medicine: Treatment of mental disorders in COVID-19 survivors.

PURPOSE: The aim of this study is to explore the possible benefits of traditional Chinese medicine on the pathogenesis of psychological and mental health of COVID-19 survivors. METHODS: A literature search was conducted to confirm the effects of COVID-19 on psychological and mental health of survivors. In addition to this, on the basis of signs and symptoms, TCM were used on treat mental disorder as per suggested clinical and animal experimental data plus relevant records in classical Chinese medicine books written by Zhang Zhongiing during Han Dynasty. A series of treatment plans were prescribed for COVID-19 survivors with psychological and mental disorders. RESULTS: According to previous extensive studies focusing on effects on mental health of survivors, high incidence was observed in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) survivors. During investigations of mental health of COVID-19 patients and survivors, it is observed that they also had symptoms of mental disorders and immune dysfunction. Furthermore, it was also proposed that depression, anxiety and post-traumatic stress disorder (PTSD) were most common mental disorders requiring special attention after the recovery from COVID-19. The symptoms of COVID-19 were analyzed, and the TCM syndrome of the depression, anxiety and PTSD after recovered from COVID19 was interpreted as internal heat and Yin deficiency. These three mental disorders pertains the category of "Lily disease", "hysteria" and "deficient dysphoria" in TCM. CONCLUSION: Lily Bulb, Rhizoma Anemarrhena Decoction and Ganmai Dazao Decoction were used to treat depression. Suanzaoren Decoction, Huanglian Ejiao Decoction and Zhizi Chi Decoction were suggested for anxiety. Moreover, Lily Bulb, Rehmannia Decoction and Guilu Erxian Decoction were the formula for PTSD.

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression-like behaviours in mice.

Depression is the most frequent psychiatric disorder in the world. Recent evidence has shown that stress-induced GABAergic dysfunction in the nucleus accumbens (NAc) contributed to the pathophysiology of depression. However, the molecular mechanisms underlying these pathological changes remain unclear. In this study, mice were constantly treated with the chronic unpredictable mild stress (CUMS) till showing depression-like behaviours expression. GABA synthesis, release and uptake in the NAc tissue were assessed by analysing the expression level of genes and proteins of Gad-1, VGAT and GAT-3 by qRT-PCR and Western blotting. The miRNA/mRNA network regulating GABA was constructed based on the bioinformatics prediction software and further validated by dual-luciferase reporter assay in vitro and qRT-PCR in vivo, respectively. Our results showed that the expression level of GAT-3, Gad-1 and VGAT mRNA and protein significantly decreased in the NAc tissue from CUMS-induced depression-like mice than that of control mice. However, miRNA-144-3p, miRNA-879-5p, miR-15b-5p and miRNA-582-5p that directly down-regulated the expression of Gad-1, VGAT and GAT-3 were increased. In the mRNA/miRNA regulatory GABA network, Gad-1 and VGAT were directly regulated by binding seed sequence of miR-144-3p, and miR-15b-5p, miR-879-5p could be served negative post-regulators by binding to the different sites of VGAT 3'-UTR. Chronic stress causes the impaired GABA synthesis, release and uptake by up-regulating miRNAs and down-regulating mRNAs and proteins, which may reveal the molecular mechanisms for the decreased GABA concentrations in the NAc tissue of CUMS-induced depression.

Identification of key genes, pathways, and miRNA/mRNA regulatory networks of CUMS-induced depression in nucleus accumbens by integrated bioinformatics analysis.

INTRODUCTION: Major depressive disorder (MDD) is a recurrent, devastating mental disorder, which affects >350 million people worldwide, and exerts substantial public health and financial costs to society. Thus, there is a significant need to discover innovative therapeutics to treat depression efficiently. Stress-induced dysfunction in the subtype of neuronal cells and the change of synaptic plasticity and structural plasticity of nucleus accumbens (NAc) are implicated in depression symptomology. However, the molecular and epigenetic mechanisms and stresses to the NAc pathological changes in depression remain elusive. MATERIALS AND METHODS: In this study, treatment group mice were treated continually with the chronic unpredictable mild stress (CUMS) until expression of depression-like behaviors were found. Depression was confirmed with sucrose preference, novelty-suppressed feeding, forced swimming, and tail suspension tests. We applied high-throughput RNA sequencing to assess microRNA expression and transcriptional profiles in the NAc tissue from depression-like behaviors mice and control mice. The regulatory network of miRNAs/mRNAs was constructed based on the high-throughput RNA sequence and bioinformatics software predictions. RESULTS: A total of 17 miRNAs and 10 mRNAs were significantly upregulated in the NAc of CUMS-induced mice with depression-like behaviors, and 12 miRNAs and 29 mRNAs were downregulated. A series of bioinformatics analyses showed that these altered miRNAs predicted target mRNA and differentially expressed mRNAs were significantly enriched in the MAPK signaling pathway, GABAergic synapse, dopaminergic synapse, cytokine-cytokine receptor interaction, axon guidance, regulation of autophagy, and so on. Furthermore, dual luciferase report assay and qRT-PCR results validated the miRNA/mRNA regulatory network. CONCLUSION: The deteriorations of GABAergic synapses, dopaminergic synapses, neurotransmitter synthesis, as well as autophagy-associated apoptotic pathway are associated with the molecular pathological mechanism of CUMS-induced depression.

Research progress on classical traditional Chinese medicine formula Lily Bulb and Rehmannia Decoction in the treatment of depression.

Depression pertains to the category of "Emotional Diseases" in traditional Chinese medicine (TCM). Its clinical symptoms are similar to the manifestations of "lily disease" from the TCM classics Synopsis of the Golden Chamber written by Zhang Zhongjing in the Han Dynasty. Also in this book, Lily Bulb and Rehmannia Decoction (LBRD) is the formula for the treatment of "lily disease". The classical herbal formula LBRD is composed of two herbs lily bulb and fresh rehmannia juice, with the function of nourishing yin and replenishing heart and lung. It has been clinically applied to treat "lily disease" for two thousand years. In this review, we focused on recent evidence linking LBRD and depression extracting data from animal and clinical studies, summarizing the primitive dosage and producing area of genuine medicinal materials of LBRD, clinical application, pharmacological mechanism and the effective substance basis for the treatment of depression. In conclusion, we discussed existing problems and future perspective. This systematic review will seek to enhance our understanding about pharmacology mechanism, herb-prescribing and recipe-constructing, and the development of novel formula for depression treatments.