Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in many pathophysiological processes. Supplementation with NAD+ and its precursors has been demonstrated as an emerging therapeutic strategy for the diseases. NAD+ also plays an important role in the reproductive system. Here, we summarize the function of NAD+ in various reproductive diseases and review the application of NAD+ and its precursors in the preservation of reproductive capacity and the prevention of embryonic malformations. It is shown that NAD+ shows good promise as a therapeutic approach for saving reproductive capacity.

A multi-omics study reveals the therapeutic effect of Linderae Radix water extract on irritable bowel syndrome (IBS-D).

ETHNOPHARMACOLOGICAL RELEVANCE: Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. AIM OF THE STUDY: While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. MATERIALS AND METHODS: 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. RESULTS: LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. CONCLUSIONS: This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D.

Body composition change indices combined with Prognostic Nutritional Index predicts the clinical outcomes of patients with gastric cancer treated with immune checkpoint inhibitor.

OBJECTIVE: This study aimed to investigate the prognostic significance of the Prognostic Nutritional Index (PNI) in conjunction with body composition change indices, namely subcutaneous fat area (SFA) and skeletal muscle index (SMI), with regard to clinical outcomes in patients with gastric cancer (GC) undergoing immune checkpoint inhibitors (ICIs) treatment. METHODS: This retrospective investigation encompassed patients with comprehensive clinical and pathological data, inclusive of portal phase enhanced CT images. Continuous variables underwent analysis utilizing the Student t-test or Mann-Whitney U-test, while categorical variables were assessed employing the Pearson chi-squared test or Fisher test. Survival outcomes were evaluated using Kaplan-Meier survival curves and the Log-rank test. Independent prognostic indicators were determined through Cox regression analysis, and a nomogram predicting survival probability for progression-free survival (PFS) and overall survival (OS) was constructed. RESULTS: Within the PNI-SFA groups, patients in Group 1 exhibited inferior PFS and OS compared to the other two groups. Similarly, among the PNI-SMI groups, Group 1 patients demonstrated poorer PFS and OS. PNI-SMI and Eosi were identified as independent prognostic factors through Cox regression analysis. Furthermore, positive associations with patient prognosis were observed for BMI, SAF, SMI, and PNI. CONCLUSION: The comprehensive consideration of PNI-SFA and PNI-SMI proved to be a superior prognostic predictor for GC patients undergoing ICI treatment.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

High-quality genome assemblies for two Australimusa bananas (Musa spp.) and insights into regulatory mechanisms of superior fiber properties.

Bananas (Musa spp.) are monocotyledonous plants with high genetic diversity in the Musaceae family that are cultivated mainly in tropical and subtropical countries. The fruits are a popular food, and the plants themselves have diverse uses. Four genetic groups (genomes) are thought to have contributed to current banana cultivars: Musa acuminata (A genome), Musa balbisiana (B genome), Musa schizocarpa (S genome), and species of the Australimusa section (T genome). However, the T genome has not been effectively explored. Here, we present the high-quality TT genomes of two representative accessions, Abaca (Musa textilis), with high-quality natural fiber, and Utafun (Musa troglodytarum, Fe'i group), with abundant ß-carotene. Both the Abaca and Utafun assemblies comprise 10 pseudochromosomes, and their total genome sizes are 613 Mb and 619 Mb, respectively. Comparative genome analysis revealed that the larger size of the T genome is likely attributable to rapid expansion and slow removal of transposons. Compared with those of Musa AA or BB accessions or sisal (Agava sisalana), Abaca fibers exhibit superior mechanical properties, mainly because of their thicker cell walls with a higher content of cellulose, lignin, and hemicellulose. Expression of MusaCesA cellulose synthesis genes peaks earlier in Abaca than in AA or BB accessions during plant development, potentially leading to earlier cellulose accumulation during secondary cell wall formation. The Abaca-specific expressed gene MusaMYB26, which is directly regulated by MusaMYB61, may be an important regulator that promotes precocious expression of secondary cell wall MusaCesAs. Furthermore, MusaWRKY2 and MusaNAC68, which appear to be involved in regulating expression of MusaLAC and MusaCAD, may at least partially explain the high accumulation of lignin in Abaca. This work contributes to a better understanding of banana domestication and the diverse genetic resources in the Musaceae family, thus providing resources for Musa genetic improvement.

Two haplotype-resolved genome assemblies for AAB allotriploid bananas provide insights into banana subgenome asymmetric evolution and Fusarium wilt control.

Bananas (Musa spp.) are one of the world's most important fruit crops and play a vital role in food security for many developing countries. Most banana cultivars are triploids derived from inter- and intraspecific hybridizations between the wild diploid ancestor species Musa acuminate (AA) and M. balbisiana (BB). We report two haplotype-resolved genome assemblies of the representative AAB-cultivated types, Plantain and Silk, and precisely characterize ancestral contributions by examining ancestry mosaics across the genome. Widespread asymmetric evolution is observed in their subgenomes, which can be linked to frequent homologous exchange events. We reveal the genetic makeup of triploid banana cultivars and verify that subgenome B is a rich source of disease resistance genes. Only 58.5% and 59.4% of Plantain and Silk genes, respectively, are present in all three haplotypes, with >50% of genes being differentially expressed alleles in different subgenomes. We observed that the number of upregulated genes in Plantain is significantly higher than that in Silk at one-week post-inoculation with Fusarium wilt tropical race 4 (Foc TR4), which confirms that Plantain can initiate defense responses faster than Silk. Additionally, we compared genomic and transcriptomic differences among the genes related to carotenoid synthesis and starch metabolism between Plantain and Silk. Our study provides resources for better understanding the genomic architecture of cultivated bananas and has important implications for Musa genetics and breeding.

[Linderae Radix water extract treats diarrhea-predominant irritable bowel syndrome in rats: a serum metabolomics study].

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.

An oxidative stress biomarkers predict prognosis in gastric cancer patients receiving immune checkpoint inhibitor.

Objective: The development and advance of gastric cancer are inextricably linked to oxidative and antioxidant imbalance. Although immunotherapy has been shown to be clinically effective, the link between oxidative stress and gastric cancer patients treated with immune checkpoint inhibitor (ICIs) remains unknown. This study aims at looking into the prognostic value of oxidative stress scores in gastric cancer patients treated with ICIs. Methods: By taking the propagation to receiver operating characteristic (ROC) we got the best cut-off values, and divided 265 patients receiving ICIs and chemotherapy into high and low GC-Integrated Oxidative Stress Score (GIOSS) groups. We also used Kaplan-Meier and COX regression models to investigate the relationship between oxidative stress biomarkers and prognosis. Results: Through both univariate and multivariate analyses, it's shown that GIOSS severs as an independent prognostic factor for progression-free survival (PFS) and Overall survival (OS). Based on GIOSS cutoff values, patients with high GIOSS levels, compared to those with low levels exhibited shorter PFS and OS, both in the high GIOSS group, which performed poorly in the ICIs subgroup and other subgroup analyses. Conclusion: GIOSS is a biomarker that responds to systemic oxidative stress in the body and can predict prognosis in patients with gastric cancer who are taking ICIs. Additionally, it might come to medical professionals' aid in making more effective or more suitable treatment plans for gastric cancer.

A NIR-II Photoactivatable "ROS Bomb" with High-Density Cu2 O-Supported MoS2 Nanoflowers for Anticancer Therapy.

The fast conversion of hydrogen peroxide (H2 O2 ) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near-infrared light in the second region (NIR-II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high-density copper-based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high-density cuprous (Cu2 O) supported molybdenum disulfide (MoS2 ) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR-II light irradiation, the ROS intensity and maximum reaction velocity (Vmax ) produced by MC NFs are 21.6 and 33.8 times that of the non-irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre-weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS-based cancer therapy.

Combined with prognostic nutritional index and IgM for predicting the clinical outcomes of gastric cancer patients who received surgery.

Objective: Although the survival rate of patients who undergo surgery for gastric cancer has greatly improved, still many patients have a poor prognosis. This retrospective study aimed to investigate the predictive ability of the PNI-IgM score, a combined prognostic nutritional index (PNI), and immunoglobulin M (IgM), on the prognosis of patients undergoing surgery for gastric cancer. Methods: 340 patients with gastric cancer who underwent surgery from January 2016 to December 2017 were selected. The PNI-IgM score ranged from 1 to 3: score of 1, low PNI (< 48.45) and low IgM (< 0.87); score of 2, low PNI and high IgM, or high PNI and low IgM; score of 3, high PNI and high IgM. We compared the differences in disease-free survival (DFS) and overall survival (OS) among the three groups, while univariate and multivariate analyses calculated prognostic factors for DFS and OS. In addition, the nomograms were constructed based on the results of multivariate analysis to estimate the 1-, 3- and 5-year survival probability. Results: There were 67 cases in the PNI-IgM score 1 group, 160 cases in the PNI-IgM score 2 group, and 113 cases in the PNI-IgM score 3 group. The median survival times of DFS in the PNI-IgM score group 1, the PNI-IgM score group 2, and the PNI-IgM score group 3 were 62.20 months, not reached, and not reached, and 67.57 months vs. not reached vs. not reached in three groups for OS. Patients in the PNI-IgM score group 1 had a lower DFS than the PNI-IgM score group 2 (HR = 0.648, 95% CI: 0.418-1.006, P = 0.053) and the PNI-IgM score group 3 (HR = 0.337, 95% CI: 0.194-0.585, P < 0.001). In stratified analysis, PNI-IgM score 1 had a worse prognosis in the age < 60 years group and CA724 < 2.11 U/m group. Conclusion: PNI-IgM score is a novel combination of nutritional and immunological markers that can be used as a sensitive biological marker for patients with gastric cancer who undergo surgery. The lower the PNI-IgM score, the worse the prognosis.

Liposomal Silybin Improves Glucose and Lipid Metabolisms in Type 2 Diabetes Mellitus Complicated with Non-Alcoholic Fatty Liver Disease via AMPK/TGF-ß1/Smad Signaling.

Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-ß1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-ß1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.

M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects.

Systemic sclerosis (SSc, scleroderma), is an autoimmune rheumatic disease characterized by fibrosis of the skin and internal organs, and vasculopathy. Preventing fibrosis by targeting aberrant immune cells that drive extracellular matrix (ECM) over-deposition is a promising therapeutic strategy for SSc. Previous research suggests that M2 macrophages play an essential part in the fibrotic process of SSc. Targeted modulation of molecules that influence M2 macrophage polarization, or M2 macrophages, may hinder the progression of fibrosis. Here, in an effort to offer fresh perspectives on the management of scleroderma and fibrotic diseases, we review the molecular mechanisms underlying the regulation of M2 macrophage polarization in SSc-related organ fibrosis, potential inhibitors targeting M2 macrophages, and the mechanisms by which M2 macrophages participate in fibrosis.

[Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing].

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Genome-wide analysis of the polyphenol oxidase gene family reveals that MaPPO1 and MaPPO6 are the main contributors to fruit browning in Musa acuminate.

Introduction: Polyphenol oxidases (PPOs), which are widely present in plants, play an important role in the growth, development, and stress responses. They can catalyze the oxidization of polyphenols and result in the browning of damaged or cut fruit, which seriously affects fruit quality and compromises the sale of fruit. In banana (Musa acuminata, AAA group), 10 PPO genes were determined based on the availability of a high-quality genome sequence, but the role of PPO genes in fruit browning remains unclear. Methods: In this study, we analyzed the physicochemical properties, gene structure, conserved structural domains, and evolutionary relationship of the PPO gene family of banana. The expression patterns were analyzed based on omics data and verified by qRT-PCR analysis. Transient expression assay in tobacco leaves was used to identify the subcellular localization of selected MaPPOs, and we analyzed the polyphenol oxidase activity using recombinant MaPPOs and transient expression assay. Results and discussion: We found that more than two-thirds of the MaPPO genes had one intron, and all contained three conserved structural domains of PPO, except MaPPO4. Phylogenetic tree analysis revealed that MaPPO genes were categorized into five groups. MaPPOs did not cluster with Rosaceae and Solanaceae, indicating distant affinities, and MaPPO6/7/8/9/10 clustered into an individual group. Transcriptome, proteome, and expression analyses showed that MaPPO1 exhibits preferential expression in fruit tissue and is highly expressed at respiratory climacteric during fruit ripening. Other examined MaPPO genes were detectable in at least five different tissues. In mature green fruit tissue, MaPPO1 and MaPPO6 were the most abundant. Furthermore, MaPPO1 and MaPPO7 localized in chloroplasts, and MaPPO6 was a chloroplast- and Endoplasmic Reticulum (ER)-localized protein, whereas MaPPO10 only localized in the ER. In addition, the enzyme activity in vivo and in vitro of the selected MaPPO protein showed that MaPPO1 had the highest PPO activity, followed by MaPPO6. These results imply that MaPPO1 and MaPPO6 are the main contributors to banana fruit browning and lay the foundation for the development of banana varieties with low fruit browning.

Mechanism of Wuyao-Ginseng Medicine Pair in the Prevention and Treatment of Diarrhea-Type Irritable Bowel Syndrome Based on Gene Expression Omnibus Chip Data.

Based on a Gene Expression Omnibus (GEO) chip analysis combined with network pharmacology and molecular docking technology, in this study we explored the molecular targets and mechanism of the wuyao-ginseng medicine pair in the prevention and treatment of diarrhea-type irritable bowel syndrome (IBS-D). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for the chemical constituents and targets of wuyao and ginseng. The UniProt database was used to search for the target gene name. In the GEO database, IBS was searched to obtain GSE36701 and GSE14841 microarray data. We imported the intersection targets into the STRING database to construct a protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (Go) pathway analyses were performed using the Metascape database. A total of 30 active ingredients of wuyao-ginseng, 171 drug targets, 1257 IBS differentially expressed genes, and 20 drug-disease intersection genes were obtained from the GEO data. We screened the results and obtained the core active ingredients beta-sitosterol, DMPEC, Boldine, etc.; the core targets NCOA2, EGFR, VEGFA, etc.; and the key pathways P13K-Akt, MAPK, etc. The wuyao-ginseng medicine pair may be involved in inflammation-related signaling pathways, acting on disease targets such as NCOA2, EGFR, and VEGFA as well as pathways such as P13K-Akt and MAPK, thereby playing a key role in the prevention and treatment of IBS-D.

WRKY transcription factor MaWRKY49 positively regulates pectate lyase genes during fruit ripening of Musa acuminata.

Fruit ripening is the last phase of fruit growth and development. The initiation and progression of fruit ripening are highly modulated by a plethora of key genes, such as transcription factor (TF) genes. The WRKY gene family is a large group of TFs that play important roles in various cellular processes; nevertheless, the role of WRKY TF on fruit ripening remains enigmatic. Here, we report that a banana WRKY TF, MaWRKY49 functions in ethylene-induced fruit ripening by modulating the expression of fruit softening-related genes. We found that the expression of MaWRKY49 is highly induced by ethephon and inhibited by 1-methylcyclopropene, which is synchronous with the ripening process. Moreover, based on transcriptome data on fruit ripening, two pectate lyase (PL) genes that are involved in fruit softening were determined, and their expression pattern is also consistent with the fruit ripening process. Yeast one-hybrid and dual-luciferase assay confirmed that MaWRKY49 activated the transcription of two PL genes. In addition, transient overexpression of MaWRKY49 in banana fruits can apparently accelerate fruit ripening processs. Taken together, our findings indicate that MaWRKY49 acts as a potential modulator of fruit ripening by direct regulation of PL expression. This work contributes to developing the technology for improving the shelf-life of banana fruit.

TCMSID: a simplified integrated database for drug discovery from traditional chinese medicine.

Traditional Chinese Medicine (TCM) has been widely used in the treatment of various diseases for millennia. In the modernization process of TCM, TCM ingredient databases are playing more and more important roles. However, most of the existing TCM ingredient databases do not provide simplification function for extracting key ingredients in each herb or formula, which hinders the research on the mechanism of actions of the ingredients in TCM databases. The lack of quality control and standardization of the data in most of these existing databases is also a prominent disadvantage. Therefore, we developed a Traditional Chinese Medicine Simplified Integrated Database (TCMSID) with high storage, high quality and standardization. The database includes 499 herbs registered in the Chinese pharmacopeia with 20,015 ingredients, 3270 targets as well as corresponding detailed information. TCMSID is not only a database of herbal ingredients, but also a TCM simplification platform. Key ingredients from TCM herbs are available to be screened out and regarded as representatives to explore the mechanism of TCM herbs by implementing multi-tool target prediction and multilevel network construction. TCMSID provides abundant data sources and analysis platforms for TCM simplification and drug discovery, which is expected to promote modernization and internationalization of TCM and enhance its international status in the future. TCMSID is freely available at https://tcm.scbdd.com .

Evaluation of Resistance of Banana Genotypes with AAB Genome to Fusarium Wilt Tropical Race 4 in China.

Banana cultivars with the AAB genome group comprise diverse subgroups, such as Plantain, Silk, Iholena, and Pisang Raja, among others, which play an important role in food security in many developing countries. Some of these cultivars are susceptible to Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), the most destructive pathogen threatening banana production worldwide, and some of them are still largely unknown. We evaluated the resistance of 37 banana genotypes, including Plantain, Silk, Iholena, Maia Maoli/Popoulu, Pisang Raja, Pome, and Mysore, to Foc TR4 under both greenhouse and field conditions. Genotypes from the Silk and Iholena subgroups were highly susceptible to Foc TR4. Pome and Mysore showed resistance and intermediate resistance, respectively. However, Pisang Raja ranged from susceptible to intermediate resistance. One cultivar from the Maia Maoli/Popoulu subgroup was highly susceptible, while the other displayed significant resistance. Most Plantain cultivars exhibited high resistance to Foc TR4, except two French types of cultivar, 'Uganda Plantain' and 'Njombe N°2', which were susceptible. The susceptibility to Foc TR4 of some of the AAB genotypes evaluated, especially Plantain and other cooking bananas, indicates that growers dependent on these varieties need to be included as part of the prevention and integrated Foc TR4 management strategies, as these genotypes play a crucial role in food security and livelihoods.

Epigallocatechin-3-gallate Mo nanoparticles (EGM NPs) efficiently treat liver injury by strongly reducing oxidative stress, inflammation and endoplasmic reticulum stress.

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.