Quantitative analysis of six sesquiterpene glycosides from Dendrobium nobile Lindl. under different growth conditions by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry in MRM mode.

INTRODUCTION: The sesquiterpene glycosides (SGs) from Dendrobium nobile Lindl. have immunomodulatory effects. However, there are no studies on the growth conditions affecting its contents and quantitative analysis methods. OBJECTIVE: In the present study, a quantitative analysis method for six SGs from D. nobile was established. We explored which growth conditions could affect the contents of SGs, providing a basis for the cultivation and clinical application of D. nobile. METHODS: Firstly, based on the optimization of mass spectrometry parameters and extraction conditions for six SGs in D. nobile, a method for the determination of the contents of six SGs was established using high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS) in multiple reaction monitoring (MRM) mode. Then, the methodology of the established method was validated. Secondly, the established method was applied to determine the contents of six SGs from 78 samples of D. nobile grown under different growth conditions. Finally, chemometrics analysis was employed to analyze the results and select optimal growth conditions for D. nobile. RESULTS: The results indicated significant variations in the contents of SGs from D. nobile grown under different growth conditions. The primary factors influencing SG contents included age, geographical origin, altitude, and epiphytic pattern. CONCLUSION: Therefore, the established method for determining SG contents from D. nobile is stable. In particular, the SG contents were relatively high in samples of 3-year-old D. nobile grown at an altitude of approximately 500 m on Danxia rocks in Chishui, Guizhou.

Glutathionylation of a glycolytic enzyme promotes cell death and vigor loss during aging of elm seeds.

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death (PCD)-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial pro-apoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N, N, N', N'-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a pro-apoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.

Identification of m6A-related lncRNAs LINC02471 and DOCK9-DT as potential biomarkers for thyroid cancer.

Thyroid cancer (THCA) is the most common endocrine malignancy worldwide and has been rising at the fastest rate in recent years. Long-stranded non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been associated with immunotherapy efficacy and cancer prognosis. However, how m6A-associated lncRNAs (mrlncRNAs) affect the prognosis of patients with thyroid cancer is unclear. Therefore, this study utilized The Cancer Genome Atlas (TCGA) database to provide thyroid cancer-related transcriptomic data and related clinical data. The R program was used to identify m6A-related lncRNAs, and a risk model consisting of two lncRNAs (LINC02471 and DOCK9-DT) was obtained using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Kaplan-Meier survival analysis and transient subject operating characteristics (ROC) were used for analysis. The results showed a substantial association between immune cell infiltration and risk scores. Independent analyses confirmed that the expression of LINC02471 and DOCK9-DT was significantly higher in thyroid cancer tissues than in normal tissues, suggesting that they may be useful biomarkers for thyroid cancer.

Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer.

BACKGROUND: Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value. AIM: To identify potential DNA methylation markers specific to ADE and CRC. METHODS: Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape. RESULTS: Comparing 22 CRC and 25 ADE samples, global methylation was higher in the former, but both showed similar methylation patterns regarding differentially methylated gene positions, chromatin signatures, and repeated elements. High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. Combined with RNA-seq gene expression data, we identified 14 methylation-regulated differentially expressed genes, of which only AGTR1 and NECAB1 methylation had prognostic significance. CONCLUSION: Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC, suggesting prognostic biomarkers for CRC.

Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. AIM OF THE STUDY: This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. METHODS: A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. RESULTS: Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. CONCLUSION: This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.

Abnormal functional connectivity of the reward circuit associated with early satiety in patients with postprandial distress syndrome.

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

Metabolites rapid-annotation in mice by comprehensive method of virtual polygons and Kendric mass loss filtering: A case study of Dendrobium nobile Lindl.

With significant advancements in high-resolution mass spectrometry, there has been a substantial increase in the amount of chemical component data acquired from natural products. Therefore, the rapid and efficient extraction of valuable mass spectral information from large volumes of high-resolution mass spectrometry data holds crucial significance. This study illustrates a targeted annotation of the metabolic products of alkaloid and sesquiterpene components from Dendrobium nobile (D. nobile) aqueous extract in mice serum through the integration of an in-houses database, R programming, a virtual metabolic product library, polygonal mass defect filtering, and Kendrick mass defect strategies. The research process involved initially establishing a library of alkaloids and sesquiterpenes components and simulating 71 potential metabolic reactions within the organism using R programming, thus creating a virtual metabolic product database. Subsequently, employing the virtual metabolic product library allowed for polygonal mass defect filtering, rapidly screening 1705 potential metabolites of alkaloids and 3044 potential metabolites of sesquiterpenes in the serum. Furthermore, based on the chemical composition database of D. nobile and online mass spectrometry databases, 95 compounds, including alkaloids, sesquiterpenes, and endogenous components, were characterized. Finally, utilizing Kendrick mass defect analysis in conjunction with known alkaloids and sesquiterpenes targeted screening of 209 demethylation, methylation, and oxidation products in phase I metabolism, and 146 glucuronidation and glutathione conjugation products in phase II metabolism. This study provides valuable insights for the rapid and accurate annotation of chemical components and their metabolites in vivo within natural products.

Construction of in vitro liver-on-a-chip models and application progress.

The liver is the largest internal organ of the human body. It has a complex structure and function and plays a vital role in drug metabolism. In recent decades, extensive research has aimed to develop in vitro models that can simulate liver function to demonstrate changes in the physiological and pathological environment of the liver. Animal models and in vitro cell models are common, but the data obtained from animal models lack relevance when applied to humans, while cell models have limited predictive ability for metabolism and toxicity in humans. Recent advancements in tissue engineering, biomaterials, chip technology, and 3D bioprinting have provided opportunities for further research in in vitro models. Among them, liver-on-a-Chip (LOC) technology has made significant achievements in reproducing the in vivo behavior, physiological microenvironment, and metabolism of cells and organs. In this review, we discuss the development of LOC and its research progress in liver diseases, hepatotoxicity tests, and drug screening, as well as chip combinations. First, we review the structure and the physiological function of the liver. Then, we introduce the LOC technology, including general concepts, preparation materials, and methods. Finally, we review the application of LOC in disease modeling, hepatotoxicity tests, drug screening, and chip combinations, as well as the future challenges and directions of LOC.

Genomic insight into the origin, domestication, dispersal, diversification and human selection of Tartary buckwheat.

BACKGROUND: Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. RESULTS: Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency. CONCLUSIONS: This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.

Neuroimaging research progress of acupuncture treatment for patients with functional dyspepsia. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯çš„ç¥žç»å½±åƒå­¦ç ”ç©¶è¿›å±•.

Neuroimaging technology provides objective and visualized research tool to study the mechanisms of acupuncture effects. Building on a systematic review of previous clinical studies on acupuncture treatment for functional dyspepsia using neuroimaging technology, this paper summarizes and synthesizes past researches from 4 aspects： acupoint-specific effects, factors influencing the effects, different physiological responses, and predictive factors for acupuncture efficacy. It suggests that acupuncture treatment for FD involves central integration with disease-targeted (acupuncture treatment can target and regulate abnormal brain functional activity patterns in patients with FD), meridian-specific (stimulation of specific acupuncture points along the stomach meridian can significantly regulate abnormal brain functional activity patterns in FD patients), and dynamic conditional features(the effects of acupuncture treatment for FD are influenced by multiple factors). Lastly, considering the current research status, this paper outlines prospects in terms of research subjects, influencing factors, and result validation, aiming to provide references for future in-depth research.

Hypoglycemic Effects and Quality Marker Screening of Dendrobium nobile Lindl. at Different Growth Years.

(1) Background: The effect of Dendrobium nobile Lindl. (D. nobile) on hyperglycemic syndrome has only been recently known for several years. Materials of D. nobile were always collected from the plants cultivated in various growth ages. However, regarding the efficacy of D. nobile on hyperglycemic syndrome, it was still unknown as to which cultivation age would be selected. On the other hand, with the lack of quality markers, it is difficult to control the quality of D. nobile to treat hyperglycemic syndrome. (2) Methods: The effects of D. nobile cultivated at year 1 and year 3 were checked on alloxan-induced diabetic mice while their body weight, diet, water intake, and urinary output were monitored. Moreover, levels of glycosylated serum protein and insulin were measured using Elisa kits. The constituents of D. nobile were identified and analyzed by using UPLC-Q/trap. Quality markers were screened out by integrating the data from UPLC-Q/trap into a network pharmacology model. (3) Results: The D. nobile cultivated at both year 1 and year 3 showed a significant effect on hyperglycemic syndrome at the high dosage level; however, regarding the significant level, D. nobile from year 1 showed the better effect. In D. nobile, most of the metabolites were identified as alkaloids and sesquiterpene glycosides. Alkaloids, represented by dendrobine, were enriched in D. nobile from year 1, while sesquiterpene glycosides were enriched in D. nobile from year 3. Twenty one metabolites were differentially expressed between D. nobile from year 1 and year 3. The aforementioned 21 metabolites were enriched to 34 therapeutic targets directly related to diabetes. (4) Conclusions: Regarding the therapy for hyperglycemic syndrome, D. nobile cultivated at year 1 was more recommended than that at year 3. Alkaloids were recommended to be used as markers to control the quality of D. nobile for hyperglycemic syndrome treatment.

PPARα is one of the key targets for dendrobine to improve hepatic steatosis in NAFLD.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. (DNL) is a traditional Chinese ethnobotanical herb. Dendrobine (DNE) has been designated as a quality indicator for DNL in the Chinese Pharmacopoeia. DNE exhibits various pharmacological activities, including the reduction of blood lipids, regulation of blood sugar levels, as well as anti-inflammatory and antioxidant properties. AIM OF THE STUDY: The objective of this study is to explore the impact of DNE on lipid degeneration in nonalcoholic fatty liver disease (NAFLD) liver cells and elucidate its specific mechanism. The findings aim to offer theoretical support for the development of drugs related to DNL. MATERIALS AND METHODS: We utilized male C57BL/6J mice, aged 6 weeks old, to establish a NAFLD model. This model allowed us to assess the impact of DNE on liver pathology and lipid levels in NAFLD mice. We investigated the mechanism of DNE's regulation of lipid metabolism through RNA-seq analysis. Furthermore, a NAFLD model was established using HepG2 cells to further evaluate the impact of DNE on the pathological changes of NAFLD liver cells. The potential mechanism of DNE's improvement was rapidly elucidated using HT-qPCR technology. These results were subsequently validated using mouse liver samples. Following the in vitro activation or inhibition of PPARα function, we observed changes in DNE's ability to ameliorate pathological changes in NAFLD hepatocytes. This mechanism was further verified through RT-qPCR and Western blot analysis. RESULTS: DNE demonstrated a capacity to enhance serum TC, TG, and liver TG levels in mice, concurrently mitigating liver lipid degeneration. RNA-seq analysis unveiled that DNE primarily modulates the expression of genes related to metabolic pathways in mouse liver. Utilizing HT-qPCR technology, it was observed that DNE markedly regulates the expression of genes associated with the PPAR signaling pathway in liver cells. Consistency was observed in the in vivo data, where DNE significantly up-regulated the expression of PPARα mRNA and its protein level in mouse liver. Additionally, the expression of fatty acid metabolism-related genes (ACOX1, CPT2, HMGCS2, LPL), regulated by PPARα, was significantly elevated following DNE treatment. In vitro experiments further demonstrated that DNE notably ameliorated lipid deposition, peroxidation, and inflammation levels in NAFLD hepatocytes, particularly when administered in conjunction with fenofibrate. Notably, the PPARα inhibitor GW6471 attenuated these effects of DNE. CONCLUSIONS: In summary, DNE exerts its influence on the expression of genes associated with downstream fat metabolism by regulating PPARα. This regulatory mechanism enhances liver lipid metabolism, mitigates lipid degeneration in hepatocytes, and ultimately ameliorates the pathological changes in NAFLD hepatocytes.

Extracellular vesicles of Bacteroides fragilis regulated macrophage polarization through promoted Sema7a expression.

Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage. BF-EV promote macrophage M1/M2 polarization significantly, and increase Sting expression significantly. Bioinformatics analysis found that Sema7a is an important gene involving in macrophage polarization. The expression of Sema7a can be induced by BF-EV and can be inhibited after C-176 treated. The inhibition expression of Sema7a prevent BF-EV to induce macrophage polarization. Further analysis reveals that there is no direct interaction between Sting and Sema7a, but Sgpl1 can interact with Sting or Sema7a. BF-EV promote the expression of Sgpl1, which the phenomenon can be inhibited after C-176 treated. Importantly, overexpression of Sgpl1 reversed the effect of C-176 for Sema7a expression, while inhibit Sema7a expression has limitation influence for Sting and Sgpl1 expression. In conclusion, this study confirms that Sting-Sgpl1-Sema7a is a key mechanism by which BF-EV regulates macrophage polarization.

Multi-omics identification of a key glycosyl hydrolase gene FtGH1 involved in rutin hydrolysis in Tartary buckwheat (Fagopyrum tataricum).

Rutin, a flavonoid rich in buckwheat, is important for human health and plant resistance to external stresses. The hydrolysis of rutin to quercetin underlies the bitter taste of Tartary buckwheat. In order to identify rutin hydrolysis genes, a 200 genotypes mini-core Tartary buckwheat germplasm resource was re-sequenced with 30-fold coverage depth. By combining the content of the intermediate metabolites of rutin metabolism with genome resequencing data, metabolite genome-wide association analyses (GWAS) eventually identified a glycosyl hydrolase gene FtGH1, which could hydrolyse rutin to quercetin. This function was validated both in Tartary buckwheat overexpression hairy roots and in vitro enzyme activity assays. Mutation of the two key active sites, which were determined by molecular docking and experimentally verified via overexpression in hairy roots and transient expression in tobacco leaves, exhibited abnormal subcellular localization, suggesting functional changes. Sequence analysis revealed that mutation of the FtGH1 promoter in accessions of two haplotypes might be necessary for enzymatic activity. Co-expression analysis and GWAS revealed that FtbHLH165 not only repressed FtGH1 expression, but also increased seed length. This work reveals a potential mechanism behind rutin metabolism, which should provide both theoretical support in the study of flavonoid metabolism and in the molecular breeding of Tartary buckwheat.

BnPLP1 Positively Regulates Flowering Time, Plant Height, and Main Inflorescence Length in Brassica napus.

Protein prenylation mediated by the Arabidopsis thaliana PLURIPETALA (AtPLP) gene plays a crucial role in plant growth, development, and environmental response by adding a 15-carbon farnesyl group or one to two 20-carbon geranylgeranyl groups onto one to two cysteine residues at the C-terminus of the target protein. However, the homologous genes and their functions of AtPLP in rapeseed are unclear. In this study, bioinformatics analysis and gene cloning demonstrated the existence of two homologous genes of AtPLP in the Brassica napus L. genome, namely, BnPLP1 and BnPLP2. Evolutionary analysis revealed that BnPLP1 originated from the B. rapa L. genome, while BnPLP2 originated from the B. oleracea L. genome. Genetic transformation analysis revealed that the overexpression of BnPLP1 in Arabidopsis plants exhibited earlier flowering initiation, a prolonged flowering period, increased plant height, and longer main inflorescence length compared to the wild type. Contrarily, the downregulation of BnPLP1 expression in B. napus plants led to delayed flowering initiation, shortened flowering period, decreased plant height, and reduced main inflorescence length compared to the wild type. These findings indicate that the BnPLP1 gene positively regulates flowering time, plant height, and main inflorescence length. This provides a new gene for the genetic improvement of flowering time and plant architecture in rapeseed.

Pravastatin promotes type 2 diabetes vascular calcification through activating intestinal Bacteroides fragilis to induce macrophage M1 polarization.

BACKGROUND: Pravastatin is an oral lipid-lowering drug, commonly used by patients with diabetes that is positively correlated with the occurrence of vascular calcification (VC), but the mechanism is unclear. METHODS: In this study, 16S rRNA sequencing and qRT-PCR wereused to detect the differential gut bacteria. Metabolomics and ELISA were used to analyze the differential metabolites. qRT-PCR and western blotting (WB) were used to detect genes expression. Flow cytometry was used to analyze macrophage phenotype. Immunohistochemistry was used to analyze aortic calcification. RESULTS: We found that gut Bacteroides fragilis (BF) increased significantly in patients who took pravastatin or type 2 diabetes (T2D) mice treated with pravastatin. In vitro experiments showed that pravastatin had little effect on BF but significantly promoted BF proliferation in vivo. Further analysis showed that ArsR was an important gene for pravastatin to regulate the activation of BF, and overexpression of ArsR significantly promoted the secretion of 3,4,5-trimethoxycinnamic acid (TMCA). Importantly, pravastatin significantly promoted BF secretion of TMCA and significantly increased TMCA secretion in T2D patients or T2D mice. TMCA had little effect on vascular smooth muscle cell calcification but significantly promoted macrophage M1 polarization, which we had demonstrated that M1 macrophages promoted T2D VC. In vivo studies found that pravastatin significantly upregulated TMCA levels in the feces and serum of T2D mice transplanted with BF and promoted the macrophage M1 polarization in bone marrow and the osteoblastic differentiation of aortic cells. Similar results were obtained in T2D mice after intravenous infusion of TMCA. CONCLUSIONS: Promoting intestinal BF to secrete TMCA, which leads to macrophage M1 polarization, is an important mechanism by which pravastatin promotes calcification, and the result will be used for the optimization of clinical medication strategies of pravastatin supplying a theoretical basis and experimental basis.

Age-dependent dendrobine biosynthesis in Dendrobium nobile: insights into endophytic fungal interactions.

Introduction: Dendrobium nobile (D. nobile), a valued Chinese herb known for its diverse pharmacological effects, owes much of its potency to the bioactive compound dendrobine. However, dendrobine content varies significantly with plant age, and the mechanisms governing this variation remain unclear. This study delves into the potential role of endophytic fungi in shaping host-microbe interactions and influencing plant metabolism. Methods: Using RNA-seq, we examined the transcriptomes of 1-year-old, 2-year-old, and 3-year-old D. nobile samples and through a comprehensive analysis of endophytic fungal communities and host gene expression in D. nobile stems of varying ages, we aim to identify associations between specific fungal taxa and host genes. Results: The results revealing 192 differentially expressed host genes. These genes exhibited a gradual decrease in expression levels as the plants aged, mirroring dendrobine content changes. They were enriched in 32 biological pathways, including phagosome, fatty acid degradation, alpha-linolenic acid metabolism, and plant hormone signal transduction. Furthermore, a significant shift in the composition of the fungal community within D. nobile stems was observed along the age gradient. Olipidium, Hannaella, and Plectospherella dominated in 1-year-old plants, while Strelitziana and Trichomerium prevailed in 2-year-old plants. Conversely, 3-year-old plants exhibited additional enrichment of endophytic fungi, including the genus Rhizopus. Two gene expression modules (mediumpurple3 and darkorange) correlated significantly with dominant endophytic fungi abundance and dendrobine accumulation. Key genes involved in dendrobine synthesis were found associated with plant hormone synthesis. Discussion: This study suggests that the interplay between different endophytic fungi and the hormone signaling system in D. nobile likely regulates dendrobine biosynthesis, with specific endophytes potentially triggering hormone signaling cascades that ultimately influence dendrobine synthesis.

New dammarane-type triterpenoids from hydrolyzate of total Gynostemma pentaphyllum saponins with protein tyrosine phosphatase 1B inhibitory activity.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Enhanced performance of BiI3-incorporated CsPbBr3 solar cells.

CsPbBr3 all-inorganic perovskite solar cells (PSCs) have been extensively investigated due to their remarkable stability. However, their limited film quality and wide bandgap result in a low photoelectric conversion efficiency (PCE). In this study, BiI3 was incorporated into CsPbBr3 films to synergistically enhance light absorption and film quality. It was found that the partial substitution of Pb2+ and Br- with Bi3+ and I- in CsPbBr3 improved film quality, enhanced light absorption, and facilitated charge transfer and extraction. The device incorporating BiI3-incorporated CsPbBr3 as a light absorbing layer achieved an efficiency of 9.54%, exhibiting a significant enhancement of 19.4% compared to the undoped device. This work provides a new incorporating strategy that collaboratively improves light absorption and film quality.

Recurrence of common bile duct stones after choledocholithotomy in elderly patients: risk factor analysis and clinical prediction model development.

Background: The reasons for the recurrence of common bile duct stones (CBDS) in elderly patients after choledocholithotomy are still unclear. This study aims to establish a prediction model for CBDS recurrence by identifying risk factors. Methods: We conducted a retrospective analysis of 1804 elderly patients aged 65 years and above who were diagnosed to have CBDS and were admitted to Nanjing First Hospital between January 1, 2010, and January 1, 2021. According to inclusion and exclusion criteria, 706 patients were selected for the final analysis. The patients were assigned to two groups according to the presence or absence of CBDS recurrence, and their clinical data were then statistically analyzed. Subsequently, a prediction model and nomogram were developed, evaluating effectiveness using the concordance index (C-index). Results: Of the 706 elderly patients, 62 patients experienced CBDS recurrence after surgery, resulting in a recurrence rate of 8.8%. The multivariate Cox analysis showed that prior history of cholecystectomy (hazard ratio [HR] = 1.931, 95% confidence interval [CI]: 1.051-3.547, p = 0.034), white blood cell (WBC) count ≥11.0 × 109/L (HR = 2.923, 95% CI: 1.723-4.957, p < 0.001), preoperative total bilirubin (TBIL) level ≥ 36.5 mmol/L (HR = 2.172, 95% CI: 1.296-3.639, p = 0.003), number of stones ≥2 (HR = 2.093, 95% CI: 1.592-5.294, p = 0.001), maximum stone diameter ≥ 0.85 cm (HR = 1.940, 95% CI: 1.090-3.452, p = 0.024), and T-tube drainage (HR = 2.718, 95% CI: 1.230-6.010, p = 0.013) were independent risk factors of CBDS recurrence in elderly patients after choledocholithotomy. A postoperative CBDS recurrence prediction model was constructed with a C-index value of 0.758 (95% CI: 0.698-0.818) and internal validation value of 0.758 (95% CI: 0.641-0.875). Conclusion: A history of cholecystectomy, WBC count ≥11.0 × 109/L, preoperative TBIL level ≥ 36.5 mmol/L, number of stones ≥2, maximum stone diameter ≥ 0.85 cm, and T-tube drainage are the independent risk factors of CBDS recurrence after choledocholithotomy in elderly patients. Our developed prediction model for CBDS recurrence has good predictive ability and can help predict the prognosis of patients with CBDS.