Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

MicroRNA482/2118 is lineage-specifically involved in gibberellin signalling via the regulation of GID1 expression by targeting noncoding PHAS genes and subsequently instigated phasiRNAs.

MicroRNA482/2118 (miR482/2118) is a 22-nt miRNA superfamily, with conserved functions in disease resistance and plant development. It usually instigates the production of phased small interfering RNAs (phasiRNAs) from its targets to expand or reinforce its silencing effect. Using a new high-quality reference genome sequence and comprehensive small RNA profiling, we characterized a newly evolved regulatory pathway of miR482/2118 in litchi. In this pathway, miR482/2118 cleaved a novel noncoding trans-acting gene (LcTASL1) and triggered phasiRNAs to regulate the expression of gibberellin (GA) receptor gene GIBBERELLIN INSENSITIVE DWARF1 (GID1) in trans; another trans-acting gene LcTASL2, targeted by LcTASL1-derived phasiRNAs, produced phasiRNAs as well to target LcGID1 to reinforce the silencing effect of LcTASL1. We found this miR482/2118-TASL-GID1 pathway was likely involved in fruit development, especially the seed development in litchi. In vivo construction of the miR482a-TASL-GID1 pathway in Arabidopsis could lead to defects in flower and silique development, analogous to the phenotype of gid1 mutants. Finally, we found that a GA-responsive transcription factor, LcGAMYB33, could regulate LcMIR482/2118 as a feedback mechanism of the sRNA-silencing pathway. Our results deciphered a lineage-specifically evolved regulatory module of miR482/2118, demonstrating the high dynamics of miR482/2118 function in plants.

Photosynthesis Response and Transcriptional Analysis: Dissecting the Role of SlHB8 in Regulating Drought Resistance in Tomato Plants.

Deciphering drought resistance in crops is crucial for enhancing water productivity. Previous studies have highlighted the significant role of the transcription factor SlHB8 in regulating developmental processes in tomato plants but its involvement in drought resistance remains unclear. Here, gene overexpression (SlHB8-OE) and gene knockout (slhb8) tomato plants were utilized to study the role of SlHB8 in regulating drought resistance. Our findings showed that slhb8 plants exhibited a robust resistant phenotype under drought stress conditions. The stomata of slhb8 tomato leaves displayed significant closure, effectively mitigating the adverse effects of drought stress on photosynthetic efficiency. The slhb8 plants exhibited a decrease in oxidative damage and a substantial increase in antioxidant enzyme activity. Moreover, slhb8 effectively alleviated the degree of photoinhibition and chloroplast damage caused by drought stress. SlHB8 regulates the expression of numerous genes related to photosynthesis (such as SlPSAN, SlPSAL, SlPSBP, and SlTIC62) and stress signal transduction (such as SlCIPK25, SlABA4, and SlJA2) in response to drought stress. Additionally, slhb8 plants exhibited enhanced water absorption capacity and upregulated expression of several aquaporin genes including SlPIP1;3, SlPIP2;6, SlTIP3;1, SlNIP1;2, and SlXIP1;1. Collectively, our findings suggest that SlHB8 plays a negative regulatory role in the drought resistance of tomato plants.

Extra- and intranuclear heat perception and triggering mechanisms in plants.

The escalating impact of global warming on crop yield and quality poses a significant threat to future food supplies. Breeding heat-resistant crop varieties holds promise, but necessitates a deeper understanding of the molecular mechanisms underlying plant heat tolerance. Recent studies have shed light on the initial events of heat perception in plants. In this review, we provide a comprehensive summary of the recent progress made in unraveling the mechanisms of heat perception and response in plants. Calcium ion (Ca2+), hydrogen peroxide (H2O2), and nitric oxide (NO) have emerged as key participants in heat perception. Furthermore, we discuss the potential roles of the NAC transcription factor NTL3, thermo-tolerance 3.1 (TT3.1), and Target of temperature 3 (TOT3) as thermosensors associated with the plasma membrane. Additionally, we explore the involvement of cytoplasmic HISTONE DEACETYLASE 9 (HDA9), mRNA encoding the phytochrome-interacting factor 7 (PIF7), and chloroplasts in mediating heat perception. This review also highlights the role of intranuclear transcriptional condensates formed by phytochrome B (phyB), EARLY FLOWERING 3 (ELF3), and guanylate-binding protein (GBP)-like GTPase 3 (GBPL3) in heat perception. Finally, we raise the unresolved questions in the field of heat perception that require further investigation in the future.

Role of BraRGL1 in regulation of Brassica rapa bolting and flowering.

Gibberellin (GA) plays a major role in controlling Brassica rapa stalk development. As an essential negative regulator of GA signal transduction, DELLA proteins may exert significant effects on stalk development. However, the regulatory mechanisms underlying this regulation remain unclear. In this study, we report highly efficient and inheritable mutagenesis using the CRISPR/Cas9 gene editing system in BraPDS (phytoene desaturase) and BraRGL1 (key DELLA protein) genes. We observed a loss-of-function mutation in BraRGL1 due to two amino acids in GRAS domain. The flower bud differentiation and bolting time of BraRGL1 mutants were significantly advanced. The expression of GA-regulatory protein (BraGASA6), flowering related genes (BraSOC1, BraLFY), expansion protein (BraEXPA11) and xyloglucan endotransferase (BraXTH3) genes was also significantly upregulated in these mutants. BraRGL1-overexpressing plants displayed the contrasting phenotypes. BraRGL1 mutants were more sensitive to GA signaling. BraRGL1 interacted with BraSOC1, and the interaction intensity decreased after GA3 treatment. In addition, BraRGL1 inhibited the transcription-activation ability of BraSOC1 for BraXTH3 and BraLFY genes, but the presence of GA3 enhanced the activation ability of BraSOC1, suggesting that the BraRGL1-BraSOC1 module regulates bolting and flowering of B. rapa through GA signal transduction. Thus, we hypothesized that BraRGL1 is degraded, and BraSOC1 is released in the presence of GA3, which promotes the expression of BraXTH3 and BraLFY, thereby inducing stalk development in B. rapa. Further, the BraRGL1-M mutant promoted the flower bud differentiation without affecting the stalk quality. Thus, BraRGL1 can serve as a valuable target for the molecular breeding of early maturing varieties.

The SlARF4-SlHB8 regulatory module mediates leaf rolling in tomato.

Leaf is the main photosynthetic organ in plants and the primary energy source all along the plant life. Given the beneficial role of leaf rolling in improving photosynthetic efficiency and yield in specific environmental conditions, a better understanding of the factors and molecular mechanisms underlying this process is highly suited. Previously, the SlARF4 knocking out mutant exhibited upward curly leaf showed higher resistance to water deficit which driving us to uncover the function of SlARF4 in regulating the curly leaf formation. In this study, we unraveled the unexplored role of the SlARF4-SlHB8 module of transcription factors in the development of leaf rolling. Both SlARF4 loss-of-function and SlHB8 overexpressing tomato plants exhibited upward-rolled leaves, reflecting the active role of the two genes in controlling leaf rolling. Dual-luciferase reporter assays and phenotypic analysis of hybrid progenies suggested that SlHB8 acts downstream of SlARF4 in curly leaf formation. SlARF4 and SlHB8 influence the development of leaf palisade tissues via modulating the expression of genes associated with curly leaf formation. SEM analysis revealed no significant differences in leaf epidermal cells between the two leaf-rolling mutants and the wild type, indicating that curly leaves of arf4 and SlHB8-OE do not result from the asymmetric leaf epidermal cell growth. Our data provide novel insight into the molecular mechanism of abaxial-adaxial determination involving SlARF4 and SlHB8 and reveals that leaf rolling operates via different regulation mechanisms in tomato and Arabidopsis model plant.

How autophagy, a potential therapeutic target, regulates intestinal inflammation.

Inflammatory bowel disease (IBD) is a group of disorders that cause chronic inflammation in the intestines, with the primary types including ulcerative colitis and Crohn's disease. The link between autophagy, a catabolic mechanism in which cells clear protein aggregates and damaged organelles, and intestinal health has been widely studied. Experimental animal studies and human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation and other aspects. However, few articles have summarized and discussed the pathways by which autophagy improves or exacerbates IBD. Here, we review how autophagy alleviates IBD through the specific genes (e.g., ATG16L1, IRGM, NOD2 and LRRK2), crosstalk of multiple phenotypes with autophagy (e.g., Interaction of autophagy with endoplasmic reticulum stress, intestinal antimicrobial defense and apoptosis) and autophagy-associated signaling pathways. Moreover, we briefly discuss the role of autophagy in colorectal cancer and current status of autophagy-based drug research for IBD. It should be emphasized that autophagy has cell-specific and environment-specific effects on the gut. One of the problems of IBD research is to understand how autophagy plays a role in intestinal tract under specific environmental factors. A better understanding of the mechanism of autophagy in the occurrence and progression of IBD will provide references for the development of therapeutic drugs and disease management for IBD in the future.

Genome-wide identification of BcGRF genes in flowering Chinese cabbage and preliminary functional analysis of BcGRF8 in nitrogen metabolism.

Growth-regulating factors (GRFs) are a unique family of transcription factors with well-characterized functions in plant growth and development. However, few studies have evaluated their roles in the absorption and assimilation of nitrate. In this study, we characterized the GRF family genes of flowering Chinese cabbage (Brassica campestris), an important vegetable crop in South China. Using bioinformatics methods, we identified BcGRF genes and analyzed their evolutionary relationships, conserved motifs, and sequence characteristics. Through genome-wide analysis, we identified 17 BcGRF genes distributed on seven chromosomes. A phylogenetic analysis revealed that the BcGRF genes could be categorized into five subfamilies. RT-qPCR analysis showed that BcGRF1, 8, 10, and 17 expression clearly increased in response to nitrogen (N) deficiency, particularly at 8 h after treatment. BcGRF8 expression was the most sensitive to N deficiency and was significantly correlated with the expression patterns of most key genes related to N metabolism. Using yeast one-hybrid and dual-luciferase assays, we discovered that BcGRF8 strongly enhances the driving activity of the BcNRT1.1 gene promoter. Next, we investigated the molecular mechanism by which BcGRF8 participates in nitrate assimilation and N signaling pathways by expressing it in Arabidopsis. BcGRF8 was localized in the cell nucleus and BcGRF8 overexpression significantly increased the shoot and root fresh weights, seedling root length, and lateral root number in Arabidopsis. In addition, BcGRF8 overexpression considerably reduced the nitrate contents under both nitrate-poor and -rich conditions in Arabidopsis. Finally, we found that BcGRF8 broadly regulates genes related to N uptake, utilization, and signaling. Our results demonstrate that BcGRF8 substantially accelerates plant growth and nitrate assimilation under both nitrate-poor and -rich conditions by increasing the number of lateral roots and the expression of genes involved in N uptake and assimilation, providing a basis for crop improvement.

Yuanzhi Powder inhibits tau pathology in SAMP8 mice: Mechanism research of a traditional Chinese formula against Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanzhi Powder (YZP), a classical Chinese medicine formula, is good at tonifying heart-Qi and improving cognitive ability. YZP has been reported to show therapeutic effect on alleviating the symptoms of Alzheimer's disease (AD). AIM OF THE STUDY: This study was conducted to observe the effects of YZP on improving the cognitive abilities of SAMP8 mice, and explore the involved mechanisms on inhibiting the excessive accumulation of phosphorylated tau. MATERIAL AND METHODS: Thirty SAMP8 mice were randomly divided into five groups: AD group, AD + DO group, AD + YZP group, AD + LAC group and AD + LAC + YZP group. Age-matched SAMR1 mice were served as CTL group. AD + LAC group and AD + LAC + YZP group received 1 µg Lactacystin solution via intra-cerebroventricular injection. All mice (except the CTL group and AD + LAC group) were intragastrically administrated for 8 consecutive weeks. Then, the Morris Water Maze (MWM) test was conducted for evaluation of learning and memory abilities. The pathological changes of hippocampal CA1 were observed by Hematoxylin & eosin (H&E) staining. The expression of 26S proteasome in the hippocampus was measured by Western Blot (WB) and immunohistochemistry (IHC). The expressions of total tau (Tau5) and hyperphosphorylated tau (pS199, pT231 and pS396) were detected by WB. The aggregation of hyperphosphorylated tau and the binding ability of tau protein to microtubules were evaluated respectively by immunostaining and Thioflavin-S staining and double-label immunofluorescence. RESULTS: SAMP8 mice showed serious cognitive impairment in behavioral tests. However, treatment of YZP significantly ameliorated the cognitive deficits of SAMP8 mice. The H&E staining suggested that YZP could protect against neuronal loss in SAMP8 mice. The IHC and WB results showed that YZP increases 26S proteasome expression in SAMP8 mice and 26S proteasome expression was effectively inhibited by Lactacystin. Meanwhile, The WB results demonstrated that YZP can inhibit the expression of hyperphosphorylated tau (pT231, pS396 and pS199). Furthermore, the immunostaining and Thioflavin-S staining and double-label immunofluorescence results indicated that YZP attenuates the excessive aggregation of hyperphosphorylated tau and enhances the binding ability of tau to stabilize microtubules in SAMP8 mice. CONCLUSIONS: YZP could enhance cognitive performance and learning of AD, ameliorate tau pathology and significantly improve the binding ability of tau to microtubules, based potentially on inhibiting the excessive aggregation of hyperphosphorylated tau via the 26Sproteasome pathway but not necessarily the only one.

Neuroprotective effects and possible mechanisms of berberine in animal models of Alzheimer's disease: a systematic review and meta-analysis.

Background: Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD. Methods: We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aß1-42) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, ß-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1ß (IL-1ß), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE's risk of bias tool was used to assess the methodological quality. Results: Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency (p < 0.00001), increased times of crossing platform (p < 0.00001) and time spent in the target quadrant (p < 0.00001), decreased Aß1-42 deposition (p < 0.00001), Tau-ps 202 (p < 0.00001) and Tau-ps 404 (p = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels. Conclusion: Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5-260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.

Genome-wide identification of the KNOTTED HOMEOBOX gene family and their involvement in stalk development in flowering Chinese cabbage.

Gibberellin and cytokinin synergistically regulate the stalk development in flowering Chinese cabbage. KNOX proteins were reported to function as important regulators of the shoot apex to promote meristem activity by synchronously inducing CTK and suppressing GA biosynthesis, while their regulatory mechanism in the bolting and flowering is unknown. In this study, 9 BcKNOX genes were identified and mapped unevenly on 6 out of 10 flowering Chinese cabbage chromosomes. The BcKNOXs were divided into three subfamilies on the basis of sequences and gene structure. The proteins contain four conserved domains except for BcKNATM. Three BcKNOX TFs (BcKNOX1, BcKNOX3, and BcKNOX5) displayed high transcription levels on tested tissues at various stages. The major part of BcKNOX genes showed preferential expression patterns in response to low-temperature, zeatin (ZT), and GA3 treatment, indicating that they were involved in bud differentiation and bolting. BcKNOX1 and BcKNOX5 showed high correlation level with gibberellins synthetase, and CTK metabolic genes. BcKONX1 also showed high correlation coefficients within BcRGA1 and BcRGL1 which are negative regulators of GA signaling. In addition, BcKNOX1 interacted with BcRGA1 and BcRGL1, as confirmed by yeast two-hybrid (Y2H) and biomolecular fluorescence complementation assay (BiFC). This analysis has provided useful foundation for the future functional roles' analysis of flowering Chinese cabbage KNOX genes.

A study protocol for a randomized controlled trial to assess the efficacy of Baduanjin exercise on older adults with sarcopenia in China.

BACKGROUND: Accompanied by the decline of physiological functions, the decrease of physical activity, and comorbidities, older adults are susceptible to sarcopenia because of accelerated loss of muscle mass. Resistance training is recommended by different clinical practice guidelines. However, most older adults have difficulty in taking recommended high-load resistance training programs, and there are limited exercise options form them. Baduanjin, a traditional Chinese mind-body exercise with relatively low intensity and simple movements, has the potential benefits of improving physical functions and may be feasible in treating sarcopenia and preventing its adverse health outcomes in older patients. With the emergence of the concept of gut-muscle axis, this study aims to determine the efficacy of Baduanjin exercise on Chinese older adults with sarcopenia and explore its underlying mechanism. METHODS: This is a 24-week, assessor-blinded, randomized controlled trial. Individuals aged 60 to 84 years old will be screened for sarcopenia. 90 participants with sarcopenia will be enrolled and randomly assigned (1:1) into the Baduanjin exercise or resistance training group, and 20 participants without sarcopenia will be set as the non-sarcopenia control group. The primary outcome is the scores of Short Physical Performance Battery. The secondary outcomes are body composition, handgrip strength, walking speed, global cognitive function, and incidence of falls. These outcomes will be assessed at baseline, the 12th week and the 24th week. While stool samples from participants will be collected at baseline and the 24th week for analyzing the abundance of gut microbiome. Data will be analyzed in an intention-to-treat protocol. DISCUSSION: The results of this study will determine whether Baduanjin exercise can be an alternative non-pharmacological approach for older adults with sarcopenia. If they can show positive significance, it will promote Baduanjin exercise in clinical practice among these patients and inform further research involving exercise interventions on the optimal types, timing, and intensity to ameliorate sarcopenia for elderly people. TRIAL REGISTRATION: Chinese Clinical Trial Registry; Registration number: ChiCTR2100051871; Prospectively registered on October 8th, 2021.

The SlHB8 acts as a negative regulator in tapetum development and pollen wall formation in Tomato.

Pollen development is crucial for the fruit setting process of tomatoes, but the underlying regulatory mechanism remains to be elucidated. Here, we report the isolation of one HD-Zip III family transcription factor, SlHB8, whose expression levels decreased as pollen development progressed. SlHB8 knockout using CRISPR/Cas9 increased pollen activity, subsequently inducing fruit setting, whereas overexpression displayed opposite phenotypes. Overexpression lines under control of the 35 s and p2A11 promoters revealed that SlHB8 reduced pollen activity by affecting early pollen development. Transmission electron microscopy and TUNEL analyses showed that SlHB8 accelerated tapetum degradation, leading to collapsed and infertile pollen without an intine and an abnormal exine. RNA-seq analysis of tomato anthers at the tetrad stage showed that SlHB8 positively regulates SPL/NZZ expression and the tapetum programmed cell death conserved genetic pathway DYT1-TDF1-AMS-MYB80 as well as other genes related to tapetum and pollen wall development. In addition, DNA affinity purification sequencing, electrophoretic mobility shift assay, yeast one-hybrid assay and dual-luciferase assay revealed SlHB8 directly activated the expression of genes related to pollen wall development. The study findings demonstrate that SlHB8 is involved in tapetum development and degradation and plays an important role in anther development.

Nitric Oxide Is Essential for Melatonin to Enhance Nitrate Tolerance of Cucumber Seedlings.

Melatonin (MT) and nitric oxide (NO) in plants can function cooperatively to alleviate salt stress, sodic alkaline stress and immune response, as well as adventitious root formation. The interaction of MT and NO on the nitrate stress tolerance of cucumber seedlings are not well understood. We investigated the effects of exogenous MT, NO donor (SNP) and NO scavenger (cPTIO) on the growth; photosynthesis; characteristics of root morphological; accumulation of mineral elements, endogenous NO, MT, IAA and ABA; and related genes expression in cucumber (Cucumis sativus L. "Jin You No. 1") seedlings grown under high nitrate condition (HN). The results showed that MT and NO independently alleviated the inhibition of growth and photosynthesis capacity of cucumber seedlings under nitrate stress. NO was required for MT to enhance the root activity, root length, lateral root number and the accumulation of calcium, magnesium and iron in the roots of cucumber seedlings grown under nitrate stress. Consistently, the expression of adventitious rootless 1 gene (CsARL1) was modulated. Furthermore, exogenous MT induced accumulation of endogenous MT, NO, indole-3-acetic acid (IAA) and abscisic acid (ABA), mainly within 24 h after treatment, in which MT and NO were further increased at 48 h and 96 h, IAA and ABA were further increased at 16 h in the presence of SNP. In contrast, the accumulation of endogenous IAA, MT and ABA slightly decreased within 24 h, NO significantly decreased at 192 h in the presence of cPTIO. Correspondingly, the expression levels of genes involved in nitrogen metabolism (CsNR1 and CsNR2), MT metabolism (CsT5H, CsSNAT2 and Cs2-ODD33), auxin carriers and response factors (CsAUX1, CsGH3.5, CsARF17), ABA synthesis and catabolism (CsNCED1, CsNCED3 and CsCYP707A1) were upregulated by MT, in which CsNR1, CsNR2, CsAUX1, CsNCED3 and CsT5H were further induced in the presence of SNP in roots of cucumber seedlings. These observations indicated that NO act as a crucial factor in MT, alleviating nitrate stress through regulating the mechanism of root growth in cucumber seedlings.

The SlTPL3-SlWUS module regulates multi-locule formation in tomato by modulating auxin and gibberellin levels in the shoot apical meristem.

Malformed fruits depreciate a plant's market value. In tomato (Solanum lycopersicum), fruit malformation is associated with the multi-locule trait, which involves genes regulating shoot apical meristem (SAM) development. The expression pattern of TOPLESS3 (SlTPL3) throughout SAM development prompted us to investigate its functional significance via RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (Cas9)-mediated gene editing. Lower SlTPL3 transcript levels resulted in larger fruits with more locules and larger SAMs at the 5 d after germination (DAG5) stage. Differentially expressed genes in the SAM of wild-type (WT) and SlTPL3-RNAi plants, identified by transcriptome deep sequencing (RNA-seq), were enriched in the gibberellin (GA) biosynthesis and plant hormone signaling pathways. Moreover, exogenous auxin and paclobutrazol treatments rescued the multi-locule phenotype, indicating that SlTPL3 affects SAM size by mediating auxin and GA levels in the SAM. Furthermore, SlTPL3 interacted with WUSCHEL (SlWUS), which plays an important role in SAM size maintenance. We conducted RNA-seq and DNA affinity purification followed by sequencing (DAP-seq) analyses to identify the genes regulated by SlTPL3 and SlWUS in the SAM and to determine how they regulate SAM size. We detected 24 overlapping genes regulated by SlTPL3 and SlWUS and harboring an SlWUS-binding motif in their promoters. Furthermore, functional annotation revealed a notable enrichment for functions in auxin transport, auxin signal transduction, and GA biosynthesis. Dual-luciferase assays also revealed that SlTPL3 enhances SlWUS-mediated regulation (repression and activation) of SlPIN3 and SlGA2ox4 transcription, indicating that the SlTPL3-SlWUS module regulates SAM size by mediating auxin distribution and GA levels, and perturbations of this module result in enlarged SAM. These results provide novel insights into the molecular mechanism of SAM maintenance and locule formation in tomato and highlight the SlTPL3-SlWUS module as a key regulator.

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer's Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology.

Background: Yuanzhi powder (YZP) has been extensively investigated as a natural prescription with therapeutic benefits for Alzheimer's disease (AD). However, its active compounds and underlying immune mechanism for treating AD are still unclear. This study aimed to investigate the immune mechanism of YZP against AD through high-performance liquid chromatography (HPLC)-based network pharmacology and gene chip technology. Methods: Active components of YZP were obtained from HPLC and public databases. Subsequently, GSE5281, GSE28146, GSE29378, and GSE97760 from the Gene Expression Omnibus (GEO) database were downloaded to extract AD difference genes (DEGs). The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways, which implicate the targets of YZP for AD, were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT. Results: 83 YZP active compounds and 641 DEGs associated with AD, including quercetin, berberine, 3,6'-disinapoylsucrose, coptisine, and palmatine, were evaluated. We showed that FOS, CCL2, and GJA1 were the core targets and that the gap junction is an essential signaling pathway in YZP for AD. Furthermore, the AD group had a higher infiltration level of naïve B cells and resting CD4 memory T cells, as determined by the CIBERSORT. Notably, the immune cells-targets network demonstrates that GJA1 and GRM1 are intimately related to naïve B cells and plasma cells. Conclusions: YZP may help treat AD by targeting proteins with key active compounds to regulate naïve B cells and plasma cells. Our results demonstrate a new immune mechanism for treating AD with YZP.

Identification of BcARR Genes and CTK Effects on Stalk Development of Flowering Chinese Cabbage.

Flowering Chinese cabbage (Brassica campestris L. ssp. Chinensis var. utilis Tsen et Lee) is an important and extensively cultivated vegetable in south China, whose major food product is the stalk. In the process of stalk formation, its initiation and development are regulated by a series of hormonal signals, such as cytokinin and gibberellin. In this study, we analyzed the effects of zeatin (ZT) and gibberellin A3 (GA3), and their interaction, on the bolting of flowering Chinese cabbage. The results indicated that the three-true-leaf spraying of ZT and GA synthesis inhibitor (PAC) inhibited plant height but increased stem diameter. Cytokinin (CTK) synthesis inhibitor (YZJ) and GA3 treatment increased plant height and decreased stem diameter. In addition, ZT and GA3 co-treated plants displayed antagonistic effect. Further, 19 type-B authentic response regulators (ARR-Bs), the positive regulators of cytokinin signal transduction were identified from flowering Chinese cabbage. Comprehensive analysis of phylogeny showed BcARR-Bs clustered into three subfamilies with 10 conserved motifs. Analysis of their expression patterns in different tissues and at various growth stage, and their response to hormone treatment suggest that ARR1-b localized in the nucleus displayed unique highest expression patterns in stem tips, are responsive both to ZT and GA, suggesting a significant role in mediating the crosstalk of ZT and GA in the bolting of flowering Chinese cabbage.

Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes-Related Cognitive Impairment: A Systematic Review and Meta-Analysis of Animal Studies.

Berberine, the main bioactive component of Coptis chinensis Franch., is widely used in the treatment of diabetes. Previous studies have reported that berberine supplementation may play a multitarget therapeutic role in diabetes-related cognitive impairment (DCI). This systematic review and meta-analysis evaluated the effect and possible mechanisms of berberine in animal models of DCI. Relevant studies were searched through PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and VIP) until March 2022. Twenty studies involving 442 animals were included, and SYRCLE's risk of bias tool was used to assess methodological quality. The statistical analysis was performed using STATA 15.0 to calculate the weighted standard mean difference (SMD) with a 95% confidence interval (CI). The fasting blood glucose (FBG) and Morris water maze test (MWM) were the main outcomes to be analyzed. The overall results showed that berberine could significantly improve FBG, escape latency, the times of crossing the platform, the time spent in the target quadrant, serum insulin, 2hBG of oral glucose tolerance test (OGTT), amyloid ß (Aß), acetylcholinesterase (AChE), oxidative stress, and inflammation levels. The present meta-analysis demonstrated that berberine could not only lower blood glucose levels but also improve learning and memory in DCI animal models, which might involve regulating glucose and lipid metabolism, improving insulin resistance, anti-oxidation, anti-neuroinflammation, inhibiting endoplasmic reticulum (ER) stress; and improving the cholinergic system. However, additional attention should be paid to these outcomes due to the significant heterogeneity.

BcSOC1 Promotes Bolting and Stem Elongation in Flowering Chinese Cabbage.

Flowering Chinese cabbage is one of the most economically important stalk vegetables. However, the molecular mechanisms underlying bolting, which is directly related to stalk quality and yield, in this species remain unknown. Previously, we examined five key stem development stages in flowering Chinese cabbage. Here, we identified a gene, BcSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1), in flowering Chinese cabbage using transcriptome analysis, whose expression was positively correlated with bolting. Exogenous gibberellin (GA3) and low-temperature treatments significantly upregulated BcSOC1 and promoted early bolting and flowering. Additionally, BcSOC1 overexpression accelerated early flowering and stem elongation in both Arabidopsis and flowering Chinese cabbage, whereas its knockdown dramatically delayed bolting and flowering and inhibited stem elongation in the latter; the inhibition of stem elongation was more notable than delayed flowering. BcSOC1 overexpression also induced cell expansion by upregulating genes encoding cell wall structural proteins, such as BcEXPA11 (cell wall structural proteins and enzymes) and BcXTH3 (xyloglucan endotransglycosidase/hydrolase), upon exogenous GA3 and low-temperature treatments. Moreover, the length of pith cells was correlated with stem height, and BcSOC1 interacted with BcAGL6 (AGAMOUS-LIKE 6) and BcAGL24 (AGAMOUS-LIKE 24). Thus, BcSOC1 plays a vital role in bolting and stem elongation of flowering Chinese cabbage and may play a novel role in regulating stalk development, apart from the conserved function of Arabidopsis SOC1 in flowering alone.

SlERF.F12 modulates the transition to ripening in tomato fruit by recruiting the co-repressor TOPLESS and histone deacetylases to repress key ripening genes.

Ethylene response factors (ERFs) are downstream components of ethylene-signaling pathways known to play critical roles in ethylene-controlled climacteric fruit ripening, yet little is known about the molecular mechanism underlying their mode of action. Here, we demonstrate that SlERF.F12, a member of the ERF.F subfamily containing Ethylene-responsive element-binding factor-associated Amphiphilic Repression (EAR) motifs, negatively regulates the onset of tomato (Solanum lycopersicum) fruit ripening by recruiting the co-repressor TOPLESS 2 (TPL2) and the histone deacetylases (HDAs) HDA1/HDA3 to repress the transcription of ripening-related genes. The SlERF.F12-mediated transcriptional repression of key ripening-related genes 1-AMINO-CYCLOPROPANE-1-CARBOXYLATE SYNTHASE 2 (ACS2), ACS4, POLYGALACTURONASE 2a, and PECTATE LYASE is dependent on the presence of its C-terminal EAR motif. We show that SlERF.F12 interacts with the co-repressor TPL2 via the C-terminal EAR motif and recruits HDAs SlHDA1 and SlHDA3 to form a tripartite complex in vivo that actively represses transcription of ripening genes by decreasing the level of the permissive histone acetylation marks H3K9Ac and H3K27Ac at their promoter regions. These findings provide new insights into the ripening regulatory network and uncover a direct link between repressor ERFs and histone modifiers in modulating the transition to ripening of climacteric fruit.