Characterization of the complete chloroplast genome of the rare medicinal plant: Mandragora caulescens (Solanaceae).

In this study, we assembled high-quality chloroplast genomes of Mandragora caulescens through a reference-guided approach using high-throughput Illumina sequencing reads. The resulting chloroplast genome assembly displayed a typical quadripartite structural organization, comprising a large single-copy (LSC) region of 85,233 bp, two inverted repeat (IR) regions of 25,685 bp each, and a small single-copy (SSC) region of 18,207 bp. The chloroplast genome harbored 141 complete genes, and its overall GC content was 38.0%. In maximum-likelihood (ML) and Bayesian inference (BI) trees, the 19 Solanaceae species formed a monophyletic group, dividing into two main clades. M. caulescens and Nicandra physalodes formed a monophyletic group, suggesting a close relationship between the two species. The M. caulescens cp genome presented in this study lays a good foundation for further genetic and genomic studies of the Solanaceae.

Phylogenetic analysis and divergence time estimation of Lycium species in China based on the chloroplast genomes.

BACKGROUND: Lycium is an economically and ecologically important genus of shrubs, consisting of approximately 70 species distributed worldwide, 15 of which are located in China. Despite the economic and ecological importance of Lycium, its phylogeny, interspecific relationships, and evolutionary history remain relatively unknown. In this study, we constructed a phylogeny and estimated divergence time based on the chloroplast genomes (CPGs) of 15 species, including subspecies, of the genus Lycium from China. RESULTS: We sequenced and annotated 15 CPGs in this study. Comparative analysis of these genomes from these Lycium species revealed a typical quadripartite structure, with a total sequence length ranging from 154,890 to 155,677 base pairs (bp). The CPGs was highly conserved and moderately differentiated. Through annotation, we identified a total of 128-132 genes. Analysis of the boundaries of inverted repeat (IR) regions showed consistent positioning: the junctions of the IRb/LSC region were located in rps19 in all Lycium species, IRb/SSC between the ycf1 and ndhF genes, and SSC/IRa within the ycf1 gene. Sequence variation in the SSC region exceeded that in the IR region. We did not detect major expansions or contractions in the IR region or rearrangements or insertions in the CPGs of the 15 Lycium species. Comparative analyses revealed five hotspot regions in the CPG: trnR(UCU), atpF-atpH, ycf3-trnS(GGA), trnS(GGA), and trnL-UAG, which could potentially serve as molecular markers. In addition, phylogenetic tree construction based on the CPG indicated that the 15 Lycium species formed a monophyletic group and were divided into two typical subbranches and three minor branches. Molecular dating suggested that Lycium diverged from its sister genus approximately 17.7 million years ago (Mya) and species diversification within the Lycium species of China primarily occurred during the recent Pliocene epoch. CONCLUSION: The divergence time estimation presented in this study will facilitate future research on Lycium, aid in species differentiation, and facilitate diverse investigations into this economically and ecologically important genus.

Highly efficient fluorescent and hybrid white organic light-emitting diodes based on a bimolecular excited system: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 5771 (2023)10.1364/OL.506371.

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer.

BACKGROUND: Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. METHODS: A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. RESULTS: Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. CONCLUSION: This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.

Diagnostic Model for Alzheimer's Disease Based on PANoptosis-Related Genes.

BACKGROUND: The pathophysiology of Alzheimer's disease (AD) involves the interplay of three different processes: pyroptosis, apoptosis, and necroptosis. OBJECTIVE: To explore role of PANoptosis, a novel pro-inflammatory programmed cell death pathway, in AD patients. METHODS: We performed a consensus clustering analysis to identify distinct transcriptional profiles in the samples using the R package "ConsensusClusterPlus". The PANoptosis key genes were obtained by crossing the WGCNA brown module and differentially expressed PANoptosis genes. We accomplished regression analyses using the LASSO-Cox method, combined with pathological status and gene expression data. At the same time, we also constructed PANscore system. The expression of PANoptosis hub genes were validated by qRT-PCR in AD transgenic mice. RESULTS: Our study utilized tissue expression profile data from AD patients to construct three distinct PANoptosis patterns, each with unique molecular and clinical characteristics. We have created a risk scoring system called PANscore, which can analyze patterns specific for each AD patient. Additionally, we observed significantly lower levels of follicular helper T (Tfh) cells in the high PANscore and AD patients. Further analysis revealed a significant negative correlation of Tfh with GSDMD and MLKL. CONCLUSIONS: These findings provide a roadmap for personalized patient stratification, enabling clinicians to develop personalized treatment plans for AD patients and advance the field of precision medicine.

Highly efficient fluorescent and hybrid white organic light-emitting diodes based on a bimolecular excited system.

A bimolecular excited system is considered as a promising candidate for developing white organic light-emitting diodes (WOLEDs) with reduced phosphorescent components. However, for actualizing high-performance WOLED, little attention has been paid to electromers compared to exciplexes. Herein, we construct the bimolecular excited system to prepare fluorescent WOLEDs by combining the electromer emission with the exciplex emission, achieving a maximum power efficiency of 11.8 lm/W with a color rendering index (CRI) of over 80. Furthermore, phosphorescent dopants are doped into an exciplex host to construct hybrid WOLEDs. The fabricated complementary-color and three-color devices achieve maximum efficiencies of 55.3 cd/A (46.8 lm/W) and 34.1 cd/A (26.8 lm/W), respectively. The spectral coverages of WOLEDs are broadened by the bimolecular excited system, and CRIs are further improved at high luminance. Our strategy may bring light to the future development of highly efficient WOLEDs with economy and sustainability.

Management of Exciton Distribution for High-Performance Organic Light-Emitting Diodes Based on Interfacial Exciplex Architecture.

Interfacial exciplex has recently been adopted as an effective host to achieve phosphorescent organic light-emitting diodes (OLEDs) with high efficiencies and low driving voltages. However, a systematic understanding of exciton recombination behavior in either host of interfacial exciplex is still deficient. Herein, the strategic design rule of interfacial exciplex host is proposed to overcome the negative effects of direct trapping recombination by systematically investigating exciton recombination behavior in interfacial exciplex hosts. As a result, blue and orange phosphorescent devices acquire peak external quantum efficiencies of 23.5% and 29.2% with low turn-on voltages. These results provide a simple method to realize highly efficient OLEDs aiming for general lighting and display applications.

Characterization of the complete chloroplast genome of Cynanchum acutum subsp. sibiricum (Apocynaceae).

In this study, we assembled the complete chloroplast (cp) genome of Cynanchum acutum subsp. sibiricum using high-throughput Illumina sequencing reads. The resulting chloroplast genome assembly displayed a typical quadripartite structure with a total length of 158,283 bp, which contained a pair of inverted repeat regions (IRs) of 24,459 bp. These two IRs were separated by a large single-copy region (LSC) and a small single-copy region (SSC) of 89,424 bp and 19,941 bp in length, respectively. The C. acutum subsp. sibiricum cp genome contained 130 genes, and its overall GC content was 37.87%. Phylogenetic analysis among C. acutum subsp. sibiricum and nine other Cynanchum species demonstrated that C. acutum subsp. sibiricum was closely related to C. chinense. The C. acutum subsp. sibiricum cp genome presented in this study lays a good foundation for further genetic and genomic studies of the Cynanchum as well as Apocynaceae.

Gastrodin Ameliorates Cognitive Dysfunction in Vascular Dementia Rats by Suppressing Ferroptosis via the Regulation of the Nrf2/Keap1-GPx4 Signaling Pathway.

Gastrodia elata Bl. has a long edible history and is considered an important functional food raw material. Gastrodin (GAS) is one of the main functional substances in G. elata BI. and can be used as a health care product for the elderly to enhance resistance and delay aging. This study investigated the ameliorative effect and mechanism of GAS on cognitive dysfunction in vascular dementia (VaD) rats, which provides a theoretical basis for development and utilization of functional food. The water maze test shows that GAS improves learning and memory impairment in VaD rats. Meanwhile; GAS significantly decreased the levels of Fe2+ and malondialdehyde (MDA); increased the content of glutathione (GSH); and significantly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4), the key regulatory factors of ferroptosis; while it down-regulated the expression of kelch-like ECH-associated protein (Keap1) and cyclooxygenase 2 (COX2). However, GAS does not directly regulate GPx4 and COX2 to inhibit ferroptosis. Furthermore, compared with GAS alone, GAS combined with Bardoxolone (an agonist of Nrf2) did not further affect the increase in GPx4 levels and decrease in COX2 levels, nor did it further affect the regulation of GAS on the biochemical parameters of ferroptosis in HT22 hypoxia injury. These findings revealed that GAS inhibited ferroptosis in hippocampal neurons by activating the Nrf2/Keap1-GPx4 signaling pathway, suggesting its possible application as a functional food for improving vascular dementia by inhibiting ferroptosis.

Identification of the crosstalk among four types of adenosine-related RNA modification in pan-cancer.

Four types of A-related RNA modification regulators interact with each other and even the crosstalk between the regulators could characterize the tumor immune microenvironment infiltration patterns, chemosensitivity, and cancer prognosis in patients with pan-cancer.

Recent Advances of Interface Exciplex in Organic Light-Emitting Diodes.

The interface exciplex system is a promising technology for reaching organic light-emitting diodes (OLEDs) with low turn-on voltages, high efficiencies and long lifetimes due to its unique virtue of barrier-free charge transport, well-confined recombination region, and thermally activated delayed fluorescence characteristics. In this review, we firstly illustrate the mechanism frameworks and superiorities of the interface exciplex system. We then summarize the primary applications of interface exciplex systems fabricated by doping and doping-free technologies. The operation mechanisms of these OLEDs are emphasized briefly. In addition, various novel strategies for further improving the performances of interface exciplex-based devices are demonstrated. We believe this review will give a promising perspective and attract researchers to further develop this technology in the future.

Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease, and its underlying genes and treatments are unclear. Abnormalities in copper metabolism can prevent the clearance of ß-amyloid peptides and promote the progression of AD pathogenesis. Therefore, the present study used a bioinformatics approach to perform an integrated analysis of the hub gene based on cuproptosis that can influence the diagnosis and treatment of AD. The gene expression profiles were obtained from the Gene Expression Omnibus database, including non-demented (ND) and AD samples. A total of 2,977 cuproptosis genes were retrieved from published articles. The seven hub genes associated with cuproptosis and AD were obtained from the differentially expressed genes and WGCNA in brain tissue from GSE33000. The GO analysis demonstrated that these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic model for AD, which was validated by GES15222, GS48350, and GSE5281. In addition, immune cell infiltration of samples was investigated for correlation with these hub genes. We identified six drugs targeting these seven cuproptosis genes in DrugBank. Hence, these cuproptosis gene signatures may be an important prognostic indicator for AD and may offer new insights into treatment options.

Immune infiltration in renal cell carcinoma.

Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumor-infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS). We found that CD8+ T cells were associated with prolonged OS (hazard ratio [HR] = 0.09, 95% confidence interval [CI].01-.53; P = 0.03) in chromophobe carcinoma (KICH). A higher proportion of regulatory T cells was associated with a worse outcome (HR = 1.59, 95% CI 1.23-.06; P < 0.01) in renal clear cell carcinoma (KIRC). In renal papillary cell carcinoma (KIRP), M1 macrophages were associated with a favorable outcome (HR = .43, 95% CI .25-.72; P < 0.01), while M2 macrophages indicated a worse outcome (HR = 2.55, 95% CI 1.45-4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA4 and LAG3 were associated with a poor prognosis in KIRC, and IDO1 and PD-L2 were associated with a poor prognosis in KIRP. This study indicates TIICs are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.

A comparison of ultrasound-augmented and conventional leaching of silver from sintering dust using acidic thiourea.

In the process of steel manufacture, up to ten millions of tons of sintering dust (SD) are produced annually in China, which contain noble metals such as Ag. Therefore, recovery of silver (Ag) from SD could be a potential economic and environmental activity. The purpose of this article is to generate information about reaction kinetics of silver leaching with thiourea from SD, comparing the conventional and ultrasonic-augment leaching. The effects of various control parameters such as the ultrasound power, particle size, leaching temperature and thiourea concentration on leaching rate of silver were studied. The results showed 89% silver recovery for conventional process against 95% for ultrasound assisted leaching. The ultrasonic wave increased the leaching rate and shorten the reaction time. The rate controlling step was analyzed using shrinking core model and the rate controlling step is identified to be the diffusion through the product layer in both conventional and ultrasonic-augment leaching processes. The activation energies were estimated to be 28.01kJ/mol and 18.19kJ/mol, and the reaction order were 0.89 and 0.71, respectively.

MicroRNAs in tumor angiogenesis.

As it is necessary for tumor growth, angiogenesis has been an attractive target for drug therapy. Accumulating evidences indicate that microRNAs (miRNAs), which are short non-coding RNAs, delicately regulate the angiogenic signals through targeting angiogenic factors and protein kinases. They can modulate pro-angiogenic signals induced by vascular endothelial growth factor (VEGF) and anti-angiogenic signals induced by thrombospondin-1 (TSP-1), and therefore promote or inhibit tumor angiogenesis. Receptor tyrosine kinases (RTKs) and hypoxia inducible factor (HIF) are also targeted by miRNAs. Moreover, miRNAs crosstalk with reactive oxygen species (ROS) influencing tumor angiogenesis. It is critical to understand the role of miRNAs in tumor angiogenesis due to their therapeutic potential to improve outcome for cancer patients. The following review discusses the current state of knowledge related to tumor angiogenesis-regulatory miRNAs and their targets.

Simulated microgravity increases heavy ion radiation-induced apoptosis in human B lymphoblasts.

AIMS: Microgravity and radiation, common in space, are the main factors influencing astronauts' health in space flight, but their combined effects on immune cells are extremely limited. Therefore, the effect of simulated microgravity on heavy ion radiation-induced apoptosis, and reactive oxygen species (ROS)-sensitive apoptosis signaling were investigated in human B lymphoblast HMy2.CIR cells. MAIN METHODS: Simulated microgravity was achieved using a Rotating Wall Vessel Bioreactor at 37°C for 30 min. Heavy carbon-ion irradiation was carried out at 300 MeV/u, with a linear energy transfer (LET) value of 30 keV/µm and a dose rate of 1Gy/min. Cell survival was evaluated using the Trypan blue exclusion assay. Apoptosis was indicated by Annexin V/propidium iodide staining. ROS production was assessed by cytometry with a fluorescent probe dichlorofluorescein. Malondialdehyde was detected using a kit. Extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase phosphatase-1 (MKP-1) and caspase-3 activation were measured by immunoblotting. KEY FINDINGS: Simulated microgravity decreased heavy ion radiation-induced cell survival and increased apoptosis in HMy2.CIR cells. It also amplified heavy ion radiation-elicited intracellular ROS generation, which induced ROS-sensitive ERK/MKP-1/caspase-3 activation in HMy2.CIR cells. The above phenomena could be reversed by the antioxidants N-acetyl cysteine (NAC) and quercetin. SIGNIFICANCE: These results illustrated that simulated microgravity increased heavy ion radiation-induced cell apoptosis, mediated by a ROS-sensitive signal pathway in human B lymphoblasts. Further, the antioxidants NAC and quercetin, especially NAC, might be good candidate drugs for protecting astronauts' and space travelers' health and safety.