Tritiation of aryl thianthrenium salts with a molecular palladium catalyst.

Tritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding and receptor occupancy studies1. Tritium gas is the preferred source of tritium for the preparation of labelled molecules because it is available in high isotopic purity2. The introduction of tritium labels from tritium gas is commonly achieved by heterogeneous transition-metal-catalysed tritiation of aryl (pseudo)halides. However, heterogeneous catalysts such as palladium supported on carbon operate through a reaction mechanism that also results in the reduction of other functional groups that are prominently featured in pharmaceuticals3. Homogeneous palladium catalysts can react chemoselectively with aryl (pseudo)halides but have not been used for hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen4. Here we report a homogenous hydrogenolysis reaction with a well defined, molecular palladium catalyst. We show how the thianthrene leaving group-which can be introduced selectively into pharmaceuticals by late-stage C-H functionalization5-differs in its coordinating ability to relevant palladium(II) catalysts from conventional leaving groups to enable the previously unrealized catalysis with dihydrogen. This distinct reactivity combined with the chemoselectivity of a well defined molecular palladium catalyst enables the tritiation of small-molecule pharmaceuticals that contain functionality that may otherwise not be tolerated by heterogeneous catalysts. The tritiation reaction does not require an inert atmosphere or dry conditions and is therefore practical and robust to execute, and could have an immediate impact in the discovery and development of pharmaceuticals.

Retinal Dysfunction in a Mouse Model of HCN1 Genetic Epilepsy.

Pathogenic variants in HCN1 are associated with a range of epilepsy syndromes including a developmental and epileptic encephalopathy. The recurrent de novo HCN1 pathogenic variant (M305L) results in a cation leak, allowing the flux of excitatory ions at potentials where the wild-type channels are closed. The Hcn1M294L mouse recapitulates patient seizure and behavioral phenotypes. As HCN1 channels are highly expressed in rod and cone photoreceptor inner segments, where they shape the light response, mutated channels are likely to impact visual function. Electroretinogram (ERG) recordings from male and female mice Hcn1M294L mice revealed a significant decrease in the photoreceptor sensitivity to light, as well as attenuated bipolar cell (P2) and retinal ganglion cell responses. Hcn1M294L mice also showed attenuated ERG responses to flickering lights. ERG abnormalities are consistent with the response recorded from a single female human subject. There was no impact of the variant on the structure or expression of the Hcn1 protein in the retina. In silico modeling of photoreceptors revealed that the mutated HCN1 channel dramatically reduced light-induced hyperpolarization, resulting in more Ca2+ flux during the response when compared with the wild-type situation. We propose that the light-induced change in glutamate release from photoreceptors during a stimulus will be diminished, significantly blunting the dynamic range of this response. Our data highlight the importance of HCN1 channels to retinal function and suggest that patients with HCN1 pathogenic variants are likely to have a dramatically reduced sensitivity to light and a limited ability to process temporal information.SIGNIFICANCE STATEMENT Pathogenic variants in HCN1 are emerging as an important cause of catastrophic epilepsy. HCN1 channels are ubiquitously expressed throughout the body, including the retina. Electroretinogram recordings from a mouse model of HCN1 genetic epilepsy showed a marked decrease in the photoreceptor sensitivity to light and a reduced ability to respond to high rates of light flicker. No morphologic deficits were noted. Simulation data suggest that the mutated HCN1 channel blunts light-induced hyperpolarization and consequently limits the dynamic range of this response. Our results provide insights into the role HCN1 channels play in retinal function as well as highlighting the need to consider retinal dysfunction in disease caused by HCN1 variants. The characteristic changes in the electroretinogram open the possibility of using this tool as a biomarker for this HCN1 epilepsy variant and to facilitate development of treatments.

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

webTWAS: a resource for disease candidate susceptibility genes identified by transcriptome-wide association study.

The development of transcriptome-wide association studies (TWAS) has enabled researchers to better identify and interpret causal genes in many diseases. However, there are currently no resources providing a comprehensive listing of gene-disease associations discovered by TWAS from published GWAS summary statistics. TWAS analyses are also difficult to conduct due to the complexity of TWAS software pipelines. To address these issues, we introduce a new resource called webTWAS, which integrates a database of the most comprehensive disease GWAS datasets currently available with credible sets of potential causal genes identified by multiple TWAS software packages. Specifically, a total of 235 064 gene-diseases associations for a wide range of human diseases are prioritized from 1298 high-quality downloadable European GWAS summary statistics. Associations are calculated with seven different statistical models based on three popular and representative TWAS software packages. Users can explore associations at the gene or disease level, and easily search for related studies or diseases using the MeSH disease tree. Since the effects of diseases are highly tissue-specific, webTWAS applies tissue-specific enrichment analysis to identify significant tissues. A user-friendly web server is also available to run custom TWAS analyses on user-provided GWAS summary statistics data. webTWAS is freely available at http://www.webtwas.net.

Integral imaging three-dimensional display system with anisotropic backlight for the elimination of voxel aliasing and separation.

Compared with conventional scattered backlight systems, integral imaging (InIm) display system with collimated backlight can reduce the voxel size, but apparent voxel separation and severe graininess still exist in reconstructed 3D images. In this paper, an InIm 3D display system with anisotropic backlight control of sub-pixels was proposed to resolve both voxel aliasing and voxel separation simultaneously. It consists of an anisotropic backlight unit (ABU), a transmissive liquid crystal panel (LCP), and a lens array. The ABU with specific horizontal and vertical divergence angles was proposed and designed. Within the depth of field, the light rays emitted from sub-pixels are controlled precisely by the ABU to minimize the voxel size as well as stitch adjacent voxels seamlessly, thus improving the 3D image quality effectively. In the experiment, the prototype of our proposed ABU-type InIm system was developed, and the spatial frequency was nearly two times of conventional scattered backlight InIm system. Additionally, the proposed system eliminated the voxel separation which usually occurs in collimated backlight InIm system. As a result, voxels reconstructed by our proposed system were stitched in space without aliasing and separation, thereby greatly enhancing the 3D resolution and image quality.

Roles of increased NUCKS1 expression in endometriosis.

BACKGROUND: Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear. METHODS: Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups. RESULTS: (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF. CONCLUSION: (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Improvement of Rice Blast Resistance in TGMS Line HD9802S through Optimized Anther Culture and Molecular Marker-Assisted Selection.

Rice blast caused by Magnaporthe oryzae is one of the most serious rice diseases worldwide. The early indica rice thermosensitive genic male sterile (TGMS) line HD9802S has the characteristics of stable fertility, reproducibility, a high outcrossing rate, excellent rice quality, and strong combining ability. However, this line exhibits poor blast resistance and is highly susceptible to leaf and neck blasts. In this study, backcross introduction, molecular marker-assisted selection, gene chipping, anther culture, and resistance identification in the field were used to introduce the broad-spectrum blast-resistance gene R6 into HD9802S to improve its rice blast resistance. Six induction media were prepared by varying the content of each component in the culture medium. Murashige and Skoog's medium with 3 mg/L 2,4-dichlorophenoxyacetic acid, 2 mg/L 1-naphthaleneacetic acid, and 1 mg/L kinetin and N6 medium with 800 mg/L casein hydrolysate, 600 mg/L proline, and 500 mg/L glutamine could improve the callus induction rate and have a higher green seedling rate and a lower white seedling rate. Compared to HD9802S, two doubled haploid lines containing R6 with stable fertility showed significantly enhanced resistance to rice blast and no significant difference in spikelet number per panicle, 1000-grain weight, or grain shape. Our findings highlight a rapid and effective method for improving rice blast resistance in TGMS lines.

[Clinical study on the treatment of premature ejaculation with Nailifu Spray].

OBJECTIVE: To observe the effect of Nailifu Spray on the treatment of premature ejaculation. METHODS: A total of 90 patients were included in this study from January 1, 2022 to January 1, 2023. Nailifu spray was used to spray the surface of penile skin once a day, 2 sprays per session for 4 weeks.And the patients' premature ejaculation diagnostic tool (PEDT) scores, intravaginal ejaculation latency time (IELT), and international index of erectile function-5 (IIEF-5) scores were collected before and after treatment, respectively. RESUTS: The median (P25,P75) PEDT scores was 16.0(15.0,18.0) scores before treatment and 10.0(10.0,10.0) scores after treatment. The median (P25,P75) of IELT was 20.0 (10.0,30.0) s before treatment and 240.0 (180.0,300.0) s after treatment. The median (P25,P75) of IIEF-5 scores was 21.0 (21.0,22.0) scores before treatment and 21.0 (21.0,21.0) scores after treatment. Compared with baseline levels, IELT was significantly longer and PEDT scores were significantly lower, with statistically significant differences. No significant changes in IIEF-5 scores were seen. CONCLUSION: Nailifu spray treatment of premature ejaculation is accurate and effective, worthy of clinical promotion.

Correction: Structural diversity, bioactivities, and biosynthesis of natural diterpenoid alkaloids.

Correction for 'Structural diversity, bioactivities, and biosynthesis of natural diterpenoid alkaloids' by Yong Shen et al., Nat. Prod. Rep., 2020, 37, 763-796, https://doi.org/10.1039/D0NP00002G.

Abnormal expression and clinical significance of surface receptors on natural killer cells in the peripheral blood of patients with non-small cell lung cancer.

Natural killer (NK) cells typically function as frontline lymphocytes against cancer although little is known about their engagement in non-small cell lung cancer (NSCLC). This study compared the performance and activity of NK cells and their subsets in the peripheral blood of NSCLC sufferers and healthy participants. In total, 67 healthy controls (40 males; 59.7%) and 56 patients with NSCLC (35 males; 62.5%) were included (mean age, 66.6 years). Flow cytometry identified NK cells and their subpopulations in external blood, and the total number, proportion, activity, surface activating, and inhibitory receptor expression levels were determined. Results showed that NK cell surface receptors CD107a, IFN-γ, and TNF-α activity were markedly reduced in lung cancer patients compared to healthy controls. The number and ratio of NK cells within the lymphocyte population were decreased in patients. The concentration of the inhibitory receptors TIGIT, TIM-3, CD96, PD-1, and Siglec-7 were increased in patients, whereas the expression level of the activating receptor NKP30 was decreased. Moreover, the expression levels of IFN-γ, TIGIT, CD96, PD-1, and TIM-3 were correlated with the clinical phase of NSCLC. These findings suggest that surface receptors from NK cells are likely to be involved in the evolution of NSCLC.

Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK.

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.

Identification of genes associated with the biosynthesis of unsaturated fatty acid and oil accumulation in herbaceous peony 'Hangshao' (Paeonia lactiflora 'Hangshao') seeds based on transcriptome analysis.

BACKGROUND: Paeonia lactiflora 'Hangshao' is widely cultivated in China as a traditional Chinese medicine 'Radix Paeoniae Alba'. Due to the abundant unsaturated fatty acids in its seed, it can also be regarded as a new oilseed plant. However, the process of the biosynthesis of unsaturated fatty acids in it has remained unknown. Therefore, transcriptome analysis is helpful to better understand the underlying molecular mechanisms. RESULTS: Five main fatty acids were detected, including stearic acid, palmitic acid, oleic acid, linoleic acid and α-linolenic acid, and their absolute contents first increased and then decreased during seed development. A total of 150,156 unigenes were obtained by transcriptome sequencing. There were 15,005 unigenes annotated in the seven functional databases, including NR, NT, GO, KOG, KEGG, Swiss-Prot and InterPro. Based on the KEGG database, 1766 unigenes were annotated in the lipid metabolism. There were 4635, 12,304, and 18,291 DEGs in Group I (60 vs 30 DAF), Group II (90 vs 60 DAF) and Group III (90 vs 30 DAF), respectively. A total of 1480 DEGs were detected in the intersection of the three groups. In 14 KEGG pathways of lipid metabolism, 503 DEGs were found, belonging to 111 enzymes. We screened out 123 DEGs involved in fatty acid biosynthesis (39 DEGs), fatty acid elongation (33 DEGs), biosynthesis of unsaturated fatty acid (24 DEGs), TAG assembly (17 DEGs) and lipid storage (10 DEGs). Furthermore, qRT-PCR was used to analyze the expression patterns of 16 genes, including BBCP, BC, MCAT, KASIII, KASII, FATA, FATB, KCR, SAD, FAD2, FAD3, FAD7, GPAT, DGAT, OLE and CLO, most of which showed the highest expression at 45 DAF, except for DGAT, OLE and CLO, which showed the highest expression at 75 DAF. CONCLUSIONS: We predicted that MCAT, KASIII, FATA, SAD, FAD2, FAD3, DGAT and OLE were the key genes in the unsaturated fatty acid biosynthesis and oil accumulation in herbaceous peony seed. This study provides the first comprehensive genomic resources characterizing herbaceous peony seed gene expression at the transcriptional level. These data lay the foundation for elucidating the molecular mechanisms of fatty acid biosynthesis and oil accumulation for herbaceous peony.

Solanum steroidal glycoalkaloids: structural diversity, biological activities, and biosynthesis.

Covering: up to 1 October 2020Solanum steroidal glycoalkaloids (SGA), characterized by nitrogenous steroidal aglycone and glycoside residues, mainly occur in the Solanum species, including economically important edible plants such as potato, tomato, and eggplant. To date, 107 SGA assigned to six total skeletons have been identified from Solanum plants. SGA have unique structures and display significant pharmacological activities such as cytotoxic, antimicrobial, anticholesterol, and some are well-known poisons. The biosynthesis pathway, transcriptional regulation, and the evolution of SGA are also examined in detail. This report updates the chemical knowledge of the naturally occurring SGA from Solanum species, thereby providing an in-depth analysis of their diversity, biological activities, and biosynthesis.

Increased episcleral venous pressure in a mouse model of circumlimbal suture induced ocular hypertension.

PURPOSE: To investigate changes in aqueous humor dynamics during intraocular pressure (IOP) elevation induced by circumlimbal suture in mice. METHODS: Ocular hypertension (OHT) was induced by applying a circumlimbal suture behind the limbus in male adult C57BL6/J mice. In the OHT group, the suture was left in place for an average of 8 weeks (n = 10, OHT group). In the sham control group the suture was cut at 2 days (n = 9, sham group) and in the naïve control group (n = 5) no suture was implanted. IOP was measured at baseline across 3 days, 1 h post-suture implantation, and at the chronic endpoint. Anterior segments were assessed using optical coherence tomography (OCT). Episcleral venous pressure (EVP), total outflow facility (C), uveoscleral outflow (Fu) and aqueous humor flow rate (Fin) were determined using a constant-flow infusion model. RESULTS: All aqueous dynamic and chronic IOP outcome measures showed no difference between sham and naïve controls (p > 0.05) and thus these groups were combined into a single control group. IOP was elevated in OHT group compared with controls (p < 0.01). Chronic suture implantation did not change pupil size, anterior chamber depth or iridocorneal angles (p > 0.05). EVP was significantly higher in OHT eyes compared to control eyes (p < 0.01). There was no statistical difference in C, Fu and Fin between groups (p > 0.05). A significant linear correlation was found between IOP and EVP (R2 = 0.35, p = 0.001). CONCLUSIONS: Circumlimbal suture implantation in mouse eyes results in chronic IOP elevation without angle closure. Chronic IOP elevation is likely to reflect higher EVP.

Role of miR-211 in a PC12 cell model of Alzheimer's disease via regulation of neurogenin 2.

NEW FINDINGS: What is the central question of this study? What is the mechanism of miR-211 in an Alzheimer's disease cell model? What is the main finding and its importance? miR-211 was upregulated in an Alzheimer's disease cell model. It targeted neurogenin 2, reduced the activation of the phosphoinositide 3-kinase-Akt signalling pathway, inhibited the proliferation of the Alzheimer's disease cell model and promoted apoptosis. ABSTRACT: MicroRNAs (miRs) are aberrantly expressed in Alzheimer's disease (AD) patients. This study was intended to investigate the effect of miR-211 on an AD cell model and the involvement of neurogenin 2 (Ngn2). The appropriate dose and time for the effect of Aß1-42 on PC12 cells were determined to establish an AD cell model. An effect of miR-211 expression on cell viability, proliferation and apoptosis was detected after cell transfection. Online prediction and a dual luciferase reporter gene assay were utilized to confirm the binding sequence of miR-211 and Ngn2. qRT-PCR and western blot analysis were applied to measure Ngn2 expression. A gain and loss of function assay of miR-211 and Ngn2 was performed, and activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway was detected. The AD cell model was induced by Aß1-42 treatment. miR-211 expression was significantly enhanced after miR-211 transfection, leading to suppressed proliferation and promotion of apoptosis in Aß1-42 -treated PC12 cells. In addition, miR-211 could downregulate Ngn2 mRNA and protein expression, while overexpression of Ngn2 could reverse the effects of miR-211 on Aß1-42 -treated PC12 cells and significantly enhance the phosphorylated Akt and PI3K protein levels. miR-211 could inhibit growth of PC12 cells by suppressing Ngn2 expression and inactivating the PI3K-Akt signalling pathway.

Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and Its Clinical Significance.

OBJECTIVE: The clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs. METHODS: A total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features. RESULTS: A recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis. CONCLUSION: The hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.

177 Saponins, Including 11 New Compounds in Wild Ginseng Tentatively Identified via HPLC-IT-TOF-MSn, and Differences among Wild Ginseng, Ginseng under Forest, and Cultivated Ginseng.

Wild ginseng (W-GS), ginseng under forest (F-GS, planted in mountain forest and growing in natural environment), and cultivated ginseng (C-GS) were compared via HPLC-DAD and HPLC-IT-TOF-MSn. A total of 199 saponins, including 16 potential new compounds, were tentatively identified from 100 mg W-GS (177 saponins in W-GS with 11 new compounds), F-GS (56 saponins with 1 new compound), and C-GS (60 saponins with 6 new compounds). There were 21 saponins detected from all the W-GS, F-GS, and C-GS. Fifty saponins were only detected from W-GS, including 23 saponins found in ginseng for the first time. Contents of ginsenosides Re (12.36-13.91 mg/g), Rh1 (7.46-7.65 mg/g), Rd (12.94-12.98 mg/g), and the total contents (50.52-55.51 mg/g) of Rg1, Re, Rf, Rb1, Rg2, Rh1, and Rd in W-GS were remarkably higher than those in F-GS (Re 1.22-3.50 mg/g, Rh1 0.15-1.49 mg/g, Rd 0.19-1.49 mg/g, total 5.69-18.74 mg/g), and C-GS (Re 0.30-3.45 mg/g, Rh1 0.05-3.42 mg/g, Rd 0.17-1.68 mg/g, total 2.99-19.55 mg/g). Contents of Re and Rf were significantly higher in F-GS than those in C-GS (p < 0.05). Using the contents of Re, Rf, or Rb1, approximately a half number of cultivated ginseng samples could be identified from ginseng under forest. Contents of Rg1, Re, Rg2, Rh1, as well as the total contents of the seven ginsenosides were highest in ginseng older than 15 years, middle-high in ginseng between 10 to 15 years old, and lowest in ginseng younger than 10 years. Contents of Rg1, Re, Rf, Rb1, Rg2, and the total of seven ginsenosides were significantly related to the growing ages of ginseng (p < 0.10). Similarities of chromatographic fingerprints to W-GS were significantly higher (p < 0.05) for F-GS (median: 0.824) than C-GS (median: 0.745). A characteristic peak pattern in fingerprint was also discovered for distinguishing three types of ginseng. Conclusively, wild ginseng was remarkably superior to ginseng under forest and cultivated ginseng, with ginseng under forest slightly closer to wild ginseng than cultivated ginseng. The differences among wild ginseng, ginseng under forest, and cultivated ginseng in saponin compositions and contents of ginsenosides were mainly attributed to their growing ages.

The origin of Wxla provides new insights into the improvement of grain quality in rice.

Appearance and taste are important factors in rice (Oryza sativa) grain quality. Here, we investigated the taste scores and related eating-quality traits of 533 diverse cultivars to assess the relationships between-and genetic basis of-rice taste and eating-quality. A genome-wide association study highlighted the Wx gene as the major factor underlying variation in taste and eating quality. Notably, a novel waxy (Wx) allele, Wxla , which combined two mutations from Wxb and Wxin , exhibited a unique phenotype. Reduced GBSSI activity conferred Wxla rice with both a transparent appearance and good eating quality. Haplotype analysis revealed that Wxla was derived from intragenic recombination. In fact, the recombination rate at the Wx locus was estimated to be 3.34 kb/cM, which was about 75-fold higher than the genome-wide mean, indicating that intragenic recombination is a major force driving diversity at the Wx locus. Based on our results, we propose a new network for Wx evolution, noting that new Wx alleles could easily be generated by crossing genotypes with different Wx alleles. This study thus provides insights into the evolution of the Wx locus and facilitates molecular breeding for quality in rice.

Quantitative proteomics identified 3 oxidative phosphorylation genes with clinical prognostic significance in gastric cancer.

The aim of the present study was to explore the underlying mechanisms involved in gastric cancer (GC) formation using data-independent acquisition (DIA) quantitative proteomics analysis. We identified the differences in protein expression and related functions involved in biological metabolic processes in GC. Totally, 745 differentially expressed proteins (DEPs) were found in GC tissues vs. gastric normal tissues. Despite enormous complexity in the details of the underlying regulatory network, we find that clusters of proteins from the DEPs were mainly involved in 38 pathways. All of the identified DEPs involved in oxidative phosphorylation were down-regulated. Moreover, GC possesses significantly altered biological metabolic processes, such as NADH dehydrogenase complex assembly and tricarboxylic acid cycle, which is mostly consistent with that in KEGG analysis. Furthermore the higher expression of UQCRQ, NDUFB7 and UQCRC2 were positively correlated with a better prognosis, implicating these proteins may as novel candidate diagnostic and prognostic biomarkers.

Structural diversity, bioactivities, and biosynthesis of natural diterpenoid alkaloids.

Covering: 2009 to 2018. Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, are a diverse class of compounds having complex structural features with many stereocenters. The important pharmacological activities and structural complexity of the diterpenoid alkaloids have long interested scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. Since 2009, 373 diterpenoid alkaloids, assigned to 46 skeletons, have been isolated and identified from plants mostly in the Ranunculaceae family. The names, classes, molecular weight, molecular formula, NMR data, and plant sources of these diterpene alkaloids are collated here. This review will be a detailed update of the naturally occurring diterpene alkaloids reported from the plant kingdom from 2009-2018, providing an in-depth discussion of their diversity, biological activities, pharmacokinetics, toxicity, application, evolution, and biosynthesis.