Bibliometric insights into the evolution of uranium contamination reduction research topics: Focus on microbial reduction of uranium.

Confronting the threat of environment uranium pollution, decades of research have yielded advanced and significant findings in uranium bioremediation, resulting in the accumulation of tremendous amount of high-quality literature. In this study, we analyzed over 10,000 uranium reduction-related papers published from 1990 to the present in the Web of Science based on bibliometrics, and revealed some critical information on knowledge structure, thematic evolution and additional attention. Methods including contribution comparison, co-occurrence and temporal evolution analysis are applied. The results of the distribution and impact analysis of authors, sources, and journals indicated that the United States is a leader in this field of research and China is on the rise. The top keywords remained stable, primarily focused on chemicals (uranium, iron, plutonium, nitrat, carbon), characters (divers, surfac, speciat), and microbiology (microbial commun, cytochrome, extracellular polymeric subst). Keywords related to new strains, reduction mechanisms and product characteristics demonstrated the strongest uptrend, while some keywords related to mechanism and performance were clearly emerging in the past 5 years. Furthermore, the evolution of the thematic progression can be categorized into three stages, commencing with the discovery of the enzymatic reduction of hexavalent uranium to tetravalent uranium, developing in the groundwater remediation process at uranium-contaminated sites, and delving into the research on microbial reduction mechanisms of uranium. For future research, enhancing the understanding of mechanisms, improving uranium removal performance, and exploring practical applications can be considered. This study provides unique insights into microbial uranium reduction research, providing valuable references for related studies in this field.

COX19 Is a New Target of MACC1 and Promotes Colorectal Cancer Progression by Regulating Copper Transport in Mitochondria.

BACKGROUND: Recent studies have demonstrated that copper (Cu) plays an important role in the progression of tumor diseases. Metastasis associated with colon cancer protein 1 (MACC1) promotes the transcription and expression of various tumor-related genes. Cytochrome c oxidase (COX) 19, present in the cytoplasm and intermembrane space of mitochondria, may transport Cu within the mitochondria. However, the mechanism through which MACC1 regulates the Cu homeostasis mediated by COX19 remains unclear. OBJECTIVES: The aim of this study was to elucidate the mechanism through which MACC1 initiates the transcription and expression of COX19, and promotes malignant behavior in tumor cells. METHODS: Immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) analyses were conducted to analyze the expression of MACC1 and COX19 proteins and genes in tumor and normal tissues. RNA-chromatin immunoprecipitation was used to detect the transcriptional initiation of COX19 by MACC1. The effects of MACC1 and COX19 on mitochondrial activity were determined using an ATP assay kit and Cytochrome c Oxidase Assay Kit. A Cell Counting Kit-8 kit was used to detect the effect of high-dose Cu or overexpression of MACC1 and COX19 on tumor cell proliferation. A xenograft mouse model was used to analyze the effect of the COX19 overexpression on the malignant behavior of the tumors. RESULTS: Cu enhanced the proliferation, invasion, and migration and inhibited apoptosis of SW480 cells. MACC1 was highly expressed in colorectal cancer tissues and activated the expression of COX19 by binding to its promoter region of COX19. The overexpression of COX19 increased mitochondrial Cu content and enhanced the activity of mitochondrial COX and ATP content, and inhibited apoptosis, promoted tumor growth of mice. CONCLUSIONS: Our results indicate that COX19 functions as a target gene of MACC1 and regulates mitochondrial activity and promotes the progression of colorectal cancer. MACC1/COX19 may provide a novel therapeutic target for colorectal cancer.

Targeted delivery of organic small-molecule photothermal materials with engineered extracellular vesicles for imaging-guided tumor photothermal therapy.

Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.

Rapid Discrimination of Panax quinquefolium and Panax ginseng Using the Proofman-Duplex-LMTIA Technique.

This study aims to establish a rapid identification method based on the Proofman-LMTIA technique for distinguishing between Panax quinquefolium and Panax ginseng. By targeting specific 18S rDNA sequences, suitable primers and Proofman probes labeled FAM or JOE were designed for LMTIA. Initially, single-species-primer Proofman-LMTIA assays were performed separately for each ginseng type to optimize reaction temperature, assess sensitivity and specificity, and determine the detection limit. Subsequently, both sets of primers and their corresponding probes were combined in the same reaction system to further optimize reaction conditions, evaluate sensitivity, and assess stability. Finally, the developed Proofman-duplex-LMTIA technique was employed to detect P. quinquefolium and P. ginseng slices available in the market. Single-plex Proofman-LMTIA assays revealed that the optimal reaction temperature for both P. quinquefolium and P. ginseng was 62 °C. The sensitivity was as low as 1 pg/µL, with a detection limit of 0.1%, and both showed excellent specificity. The optimal temperature for Proofman-duplex-LMTIA assays was 58 °C. This method could simultaneously identify P. quinquefolium and P. ginseng. Testing 6 samples of P. ginseng and 11 samples of P. quinquefolium from the market resulted in a 100% positive rate for all samples. This study successfully established a rapid, simple, sensitive, and specific Proofman-duplex-LMTIA identification method for P. quinquefolium and P. ginseng. It provides an effective means for quality control of P. quinquefolium, P. ginseng, and related products.

Deep-Learning Terahertz Single-Cell Metabolic Viability Study.

Cell viability assessment is critical, yet existing assessments are not accurate enough. We report a cell viability evaluation method based on the metabolic ability of a single cell. Without culture medium, we measured the absorption of cells to terahertz laser beams, which could target a single cell. The cell viability was assessed with a convolution neural classification network based on cell morphology. We established a cell viability assessment model based on the THz-AS (terahertz-absorption spectrum) results as y = a = (x - b)c, where x is the terahertz absorbance and y is the cell viability, and a, b, and c are the fitting parameters of the model. Under water stress the changes in terahertz absorbance of cells corresponded one-to-one with the apoptosis process, and we propose a cell 0 viability definition as terahertz absorbance remains unchanged based on the cell metabolic mechanism. Compared with typical methods, our method is accurate, label-free, contact-free, and almost interference-free and could help visualize the cell apoptosis process for broad applications including drug screening.

Transcriptome analysis provides insights into coumarin biosynthesis in the medicinal plant Angelica dahurica cv. Yubaizhi.

Angelica dahurica roots have a long history of use in traditional Chinese medicine due to their high coumarin content. To address the increasing demand for these roots, a synthetic biology approach has been proposed. Nevertheless, our comprehension of coumarin biosynthesis and its regulation remains limited. In this study, we utilized Hiseq2500 sequencing to analyze the transcriptomes of A. dahurica at different growth stages while concurrently quantifying coumarin content. Differentially expressed gene (DEG) analysis was employed to identify key genes involved in coumarin and terpenoid backbone biosynthesis. Weighted gene co-expression network analysis (WGCNA) was applied to identify gene modules strongly associated with coumarin content, elucidating the regulatory relationships between transcription factors (TFs) and pathway genes. Furthermore, KEGG enrichment analysis was used to explore essential pathways governing coumarin biosynthesis, with the identification of hub genes. Our results indicated that total coumarin content was highest in the roots, followed by leaves and stems, across all three developmental stages. Transcriptome analysis identified a total of 92,478 genes, among which 215 and 30 genes were implicated in coumarin and terpenoid backbone biosynthesis, respectively. Within the 73 identified gene modules by WGCNA, three modules-namely aquamarine1 (comprising two OMTs, one CSE, one AACT, one HDS, two PSs, one 2OGO, four UGTs, and seven CYP450s), darkmagenta (containing one UGT and one HDR), and navajowhite2 (consisting of one HCT, three UGTs, one CYP71A25, one OMT, one CSE, one HDS, and one PT)-were strongly associated with imperatorin, oxypeucedanin, and isoimperatorin content, respectively. KEGG enrichment analysis highlighted significant enrichment of cytochrome P450, transporter, and ubiquitin system pathways. Moreover, TF-gene regulatory analysis unveiled the complexity of coumarin biosynthesis, with 17 TF families regulating 17 genes in the aquamarine1 module, 8 TF families regulating 2 genes in the darkmagenta module, and 8 TF families regulating 7 genes in the navajowhite2 module. These comprehensive findings provide valuable insights into coumarin biosynthesis in A. dahurica, facilitating future research and potential applications in traditional Chinese medicine and synthetic biology strategies.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

LUMO-Mediated Se and HOMO-Mediated Te Nanozymes for Selective Redox Biocatalysis.

Selenium (Se) and tellurium (Te) nanomaterials with novel chain-like structures have attracted widespread interest owing to their intriguing properties. Unfortunately, the still-unclear catalytic mechanisms have severely limited the development of biocatalytic performance. In this work, we developed chitosan-coated Se nanozymes with a 23-fold higher antioxidative activity than Trolox and bovine serum albumin coated Te nanozymes with stronger prooxidative biocatalytic effects. Based on density functional theory calculations, we first propose that the Se nanozyme with Se/Se2- active centers favored reactive oxygen species (ROS) clearance via a LUMO-mediated mechanism, while the Te nanozyme with Te/Te4+ active centers promoted ROS production through a HOMO-mediated mechanism. Furthermore, biological experiments confirmed that the survival rate of γ-irritated mice treated with the Se nanozyme was maintained at 100% for 30 days by inhibiting oxidation. However, the Te nanozyme had the opposite biological effect via promoting radiation oxidation. The present work provides a new strategy for improving the catalytic activities of Se and Te nanozymes.

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

Erchen decoction to reduce oxidative stress in dyslipidemia phlegm-dampness retention syndrome mice: In vivo mechanism revealed by metabolomics (liquid chromatography-mass spectrometry).

OBJECTIVE: Erchen decoction, a traditional Chinese medicine formula, can reduce the level of oxidative stress for the treatment of dyslipidemia phlegm-dampness retention syndrome (DPDRS); however, studies have not elucidated the mechanism underlying its metabolic action. Here, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic techniques were utilized to characterize the in vivo effects of Erchen decoction in achieving reduction of oxidative stress levels and understand the potential metabolic mechanisms of action. METHODS: We constructed a DPDRS animal model using a multifactorial composite modeling approach, and Erchen decoction was administered by gavage. We employed LC-MS-based metabolomic techniques in combination with serum-associated factors, gene transcription, methylation detection, and hematoxylin and eosin staining. RESULTS: In this study, the constructed animal model of DPDRS had satisfactory quality. Erchen decoction treatment reduced the levels of low-density lipoprotein cholesterol, t total cholesterol and riglyceride; it improved the endothelial structure, increased levels of serum ß-nicotinamide adenine dinucleotide phosphate and glutathione concentrations, increased aortic phosphoserine aminotransferase and phosphoserine phosphatase gene expression levels, and decreased aortic phosphoglycerate dehydrogenase methylation level. A total of 64 differential metabolites were obtained using LC-MS assay, and 34 differential metabolic pathways were obtained after enrichment. CONCLUSIONS: Erchen decoction treatment of DPDRS mice reversed lipid indexes, improved vascular endothelial structure, increased serum and aortic anti-oxidative stress factor concentration and expression levels, and decreased methylation levels, thereby reducing oxidative stress and protecting vascular endothelium. Tricarboxylic acid cycle and metabolic pathways of serum glutamine, serine, tryptophan, pyrimidine, and pyruvate were the most relevant metabolic pathways involved in reducing oxidative stress levels by Erchen decoction during DPDRS treatment; especially, mitochondrial redox homeostasis maintenance in endothelial cells may be crucial. In this work, the therapeutic potential of Erchen decoction for reducing the oxidative stress level in DPDRS was demonstrated; however, its in-depth mechanism is worth further exploration.

Study on the Mechanism of Radix Astragali against Renal Aging Based on Network Pharmacology.

Radix Astragali is widely used in the traditional Chinese medicine with the effect of antiaging. The purpose of this study is to explore the main active ingredients and targets of Radix Astragali against renal aging by network pharmacology and further to verify the mechanism of the main active ingredients in vitro. TCMSP, ETCM, and TCMID databases were used to screen active ingredients of Radix Astragali. Targets of active ingredients were predicted using BATMAN-TCM and cross validated using kidney aging-related genes obtained from GeneCards and NCBI database. Pathways enrichment and protein-protein interaction (PPI) analysis were performed on core targets. Additionally, a pharmacological network was constructed based on the active ingredients-targets-pathways. HK-2 cell was treated with D-galactose to generate a cell model of senescence. CCK-8 and ß-galactosidase were used to detect the effect of Radix Astragali active components on cell proliferation and aging. ELISA was used to detect the expression of senescence-associated secreted protein (TGF-ß and IL-6) in the cell culture supernatant. Western blot was used to detect the expression of key proteins in the SIRT1/p53 pathway. Five active ingredients (Astragaloside I, II, III, IV and choline) were identified from Radix Astragali, and all these active ingredients target a total of 128 genes. Enrichment analysis showed these genes were implicated in 153 KEGG pathways, including the p53, FoxO, and AMPK pathway. 117 proteins and 572 interactions were found in PPI network. TP53 and SIRT1 were two hub genes in PPI network, which interacted with each other. The pharmacological network showed that the five main active ingredients target on some coincident genes, including TP53 and SIRT1. These targeted genes were involved in the p53, FoxO, and AMPK pathway. Proliferation of HK-2 cells was increased by Astragaloside IV treatment compared with that of the D-Gal treatment group. However, the proliferation of the SA-ß-gal positive cells were inhibited. The expression of TGF-ß and IL-6 in the D-Gal group was higher than that in the normal group, and the treatment of Astragaloside IV could significantly reduce the expression of TGF-ß and IL-6. The expression of SIRT1 in the Astragaloside IV group was higher than that in the D-Gal group. However, the expression of p53 and p21 was less in the Astragaloside IV group than that in the D-Gal group. This study suggested that Astragaloside IV is an important active ingredient of Radix Astragali in the treatment of kidney aging via the SITR1-p53 pathway.

Bellidifolin from Gentianella acuta (Michx.) Hulten protects H9c2 cells from hydrogen peroxide-induced injury via the PI3K-Akt signal pathway.

Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten (G. acuta) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2O2) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2O2-induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3ß (GSK-3ß) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage.

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.

BACKGROUND: Ribonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development. AIM: To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2. METHODS: The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients. TCM monomers that potentially act on RRM2 were screened via literature mining. Using AutoDock software, the screened monomers were docked with the RRM2 protein. RESULTS: The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues, and it was negatively correlated with the overall survival rate of patients with the majority of tumor types. Through literature mining, we discovered that berberine, ursolic acid, gambogic acid, cinobufagin, quercetin, daphnetin, and osalmide have inhibitory effects on RRM2. The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein, which mainly interacted through hydrogen bonds and hydrophobic force. The main binding sites were Arg330, Tyr323, Ser263, and Met350. CONCLUSION: RRM2 is an important tumor therapeutic target. The TCM monomers screened have a good binding capacity with the RRM2 protein.

Cardiolipin-Targeted NIR-II Fluorophore Causes "Avalanche Effects" for Re-Engaging Cancer Apoptosis and Inhibiting Metastasis.

Restoring innate apoptosis and simultaneously inhibiting metastasis by a molecular drug is an effective cancer therapeutic approach. Herein, a large rigid and V-shaped NIR-II dye, DUT850, is rationally designed for potential cardiolipin (CL)-targeted chemo-phototheranostic application. DUT850 displays moderate NIR-II fluorescence, excellent photodynamic therapy (PDT) and photothermal therapy (PTT) performance, and ultra-high photostability. More importantly, the unique rigid V-shaped backbone, positive charge, and lipophilicity of DUT850 afford its specific recognition and efficient binding to CL; such an interaction of DUT850-CL induced a spectrum of physiological disruptions, including translocation of cytochrome c, Ca2+ overload, reactive oxygen species burst, and ATP depletion, which not only activated cancer cell apoptosis but also inhibited tumor metastasis both in vitro and in vivo. Furthermore, the tight binding of DUT850-CL improves the phototoxicity of DUT850 toward cancer cells (IC50 as low as 90 nM) under safe 808 nm laser irradiation (330 mW cm-2). Upon encapsulation into bovine serum albumin (BSA), DUT850@BSA exerted a synergetic chemo-PDT-PTT effect on the 4T1 tumor mouse model, eventually leading to solid tumor annihilation and metastasis inhibition, which could be followed in real time with the NIR-II fluorescence of DUT850. This work contributed a promising approach for simultaneously re-engaging cancer cell apoptotic networks and activating the anti-metastasis pathway by targeting a pivotal upstream effector, which will bring a medical boon for inhibition of tumor proliferation and metastasis.

[Enrichment Factors of Soil-Se in the Farmland in Shizuishan City, Ningxia].

Shizuishan is a typical exhausted resources-based city in the northern area of the Ningxia Hui autonomous region in China. In order to develop the planting industry of selenium (Se)-rich agricultural products and promote green and sustainable urban development and transformation, investigations on the quality of Se-rich land were carried out in Shizuishan City, where 7399 surface soil (0-20 cm) samples of farmlands, 30 atmospheric precipitation samples, and nine parent rocks were collected. By means of semi variogram model construction by GS+, Kriging interpolation in ArcGIS and statistics via SPSS, such as correlation analysis and mean-value analysis, the content, spatial distribution, and enrichment factors of Se-soil were analyzed. Further, the enrichment characteristics of soil Se in alkaline conditions were summarized. The results indicated that ω(Se) in surface soil was (0.26±0.12) mg·kg-1, and its spatial distribution was highly auto-correlated. The variation in Se content was related to natural factors. Along Helan Mountain, the content of Se in the surface soil was comparatively higher than that where coal mines were located. The parent rock was the principal factor that controlled the enrichment of soil Se. The physical and chemical properties of soil such as organic material, pH, and iron and manganese oxides had crucial effects on the enrichment of soil Se in a surficial environment. Compared to a strong alkaline environment, alkaline conditions were beneficial for the enrichment of Se in the surface soil.

[Research progress on regulation of mitophagy by traditional Chinese medicine in prevention and treatment of chronic kidney diseases].

The prevalence of chronic kidney disease(CKD) increases year by year and has become a highly prevalent disease, seriously affecting the quality of life of patients and bringing heavy family burden. There are many diseases causing CKD, including va-rious primary and secondary glomerulonephritis, renal tubular injury, and renal vascular lesions. Although routine medical treatment for CKD can alleviate the clinical symptoms to a certain extent, it is sometimes difficult to prevent the progression of CKD. Traditional Chinese medicine(TCM) is advantageous in high safety, few adverse reactions, and definite clinical efficacy in the treatment of CKD. The active components contained can play a synergistic effect through multiple pathways and multiple targets to delay disease progression, but its mechanism of action has not been fully elucidated. As revealed by the literature in this field in China and abroad, abnormal mitophagy is a common feature of the pathogenesis of CKD of different types. In recent years, a large number of studies have proved that the regulation of mitophagy through the PINK1/Parkin signaling pathway and mitophagy receptor pathway could delay the progression of CKD and protect renal function. Therefore, the regulation of mitophagy by TCM in the prevention and treatment of CKD through related pathways has become a potential therapeutic target in recent years. This paper reviewed the research articles on the definite efficacy of TCM in preventing and treating CKD by regulating mitophagy through relevant pathways to provide new targets and stra-tegies for preventing and treating CKD and delaying their entry into end-stage renal diseases.

Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study.

BACKGROUND: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up. FINDINGS: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators. INTERPRETATION: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population. FUNDING: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The 45-month therapy outcomes of permanent seed implantation and radical prostatectomy for prostate cancer patients.

Objective To compare the efficacy and safety-related outcomes after radical prostatectomy (RP) and permanent seed implantation (PI) using iodine-125 seeds in patients with prostate cancer. Method A retrospective analysis of 196 patients with biopsy-confirmed prostate cancer (T2-T3) was performed in this study. Forty-five patients who underwent PI using iodine-125 seeds combined with endocrine therapy or androgen deprivation therapy (ADT) were compared with 151 patients who underwent RP combined with endocrine therapy or adjuvant ADT. The efficacy and safety outcomes were compared using Kaplan-Meier curves and t-tests. Results Between the RP and PI treatment modalities, no significant difference (P > 0.05) in biochemical recurrence-free survival (BRFS) was observed using Kaplan-Meier curves, regardless of the combination of adjuvant treatment modalities. Furthermore, no significant differences were observed (P > 0.05) with respect to PSA fluctuations, albumin, leukocyte count, urinary and rectal symptoms, erectile function or quality of life (QoL) between the two therapy methods. However, significant differences in the maximum flow rate, average length of hospital stay and indwelling catheter time were observed between the two groups (P < 0.001). Conclusion Iodine-125 seed implantation significantly shortened the average length of hospital stay and indwelling catheter time compared with RP, and the haemoglobin level was significantly higher in the PI group than in the RP group; however, the maximum urine flow rate was lower after of PI than after RP. These two methods showed similar BRFS rates among prostate cancer patients.

Effects of different selenium sources on duodenum and jejunum tight junction network and growth performance of broilers in a model of fluorine-induced chronic oxidative stress.

The protective effects and underlying molecular mechanisms of sodium selenite (SS) and selenomethionine (SM) against chronic oxidative stress-induced duodenum and jejunum tight junction (TJ) network disturbance and growth inhibition of broilers were investigated in the current experiment. At the age of 1 d, 720 Lingnan Yellow broiler chicks were allocated to 4 experimental diets (with 6 replicates per diet and 30 birds per replicate) and offered either a control diet (fluorine [F] 23 mg/kg, control [CoN] group) or test diets (800 mg/kg F, high F [HF] group; 800 mg/kg F+0.15 mg selenium [Se]/kg as SS [SS group] or SM [SM group]) for 56 d. The results showed that HF group could induce chronic oxidative stress and subsequently increased (P < 0.05) proinflammatory cytokines levels of duodenum and jejunum in comparison with the CoN group. Increased proinflammatory cytokines levels of HF group promoted myosin light chain kinase (MLCK) transcription, thus leading to a decrease (P < 0.05) in TJ proteins expression of duodenum and jejunum when compared with the CoN group. A reduction of TJ proteins expression destroyed the TJ structures in the HF group, which in turn increased intestinal mucosal permeability of duodenum and jejunum and ultimately induced growth inhibition of broilers. Dietary Se supplementation could ameliorate HF-induced duodenum and jejunum TJ network impairment and growth retardation of broilers, potentially by increasing (P < 0.05) the glutathione peroxidase and thioredoxin reductase activities, reducing (P < 0.05) the reactive oxygen species and malondialdehyde levels, regulating the secretion of proinflammatory cytokines, and mediating the transcription level of MLCK in the duodenum and jejunum. Additionally, our data also suggested that the protective effects of SM were superior to those of SS. This study will provide a theoretical basis for developing SM into an efficient protective agent for intestinal mucosal barrier in poultry.

Jolkinolide B inhibits proliferation or migration and promotes apoptosis of MCF-7 or BT-474 breast cancer cells by downregulating the PI3K-Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The diterpenoids extracted from Euphorbia kansui S.L. Liou ex S.B.Ho, Euphorbia fischeriana Steud. have good antitumor effects. Jolkinolide B has anti-breast cancer effect, but it is unclear whether it has different therapeutic effects between luminal A subtype and luminal B subtype breast cancer. AIM OF THE STUDY: This study investigated the Jolkinolide B has different therapeutic, important targets and pathways effects between luminal A subtype and luminal B subtype breast cancer. MATERIALS AND METHODS: We used bioinformatics to predict the biological process and molecular mechanism of Jolkinolide B in treating two types of breast cancer. Then, in vitro, cultured MCF-7 cells and BT-474 cells were divided into control group, PI3K inhibitor + control group, Jolkinolide B group and PI3K inhibitor + Jolkinolide B group. The CCK-8 assay, Flow cytometric analysis and Transwell cell migration assay was used to detect the cell proliferation, apoptosis, and migration in each group, respectively. ELISA was used to measure the content of Akt and phosphorylated Akt (p-Akt) in cell lysis buffer. RESULTS: Compared to luminal A breast cancer, Jolkinolide B had more targets, proliferation, migration processes and KEGG pathways when treating luminal B subtype breast cancer. Jolkinolide B significantly prolonged the survival time of luminal B subtype breast cancer patients. Compared to the control group, the cell proliferation absorbance value (A value) and migration number of the two kinds of breast cancer cells in the Jolkinolide B group were decreased (P < 0.01, n = 6), and the number of apoptotic cells was increased (P < 0.01, n = 6). Compared to the Jolkinolide B group, the A value and migration number of the two types of breast cancer cells were significantly decreased in the PI3K inhibitor + Jolkinolide B group (P < 0.01, n = 6), and the number of apoptotic cells was significantly increased (P < 0.01, n = 6). In addition, compared to MCF-7 cells, the A value and migration number of BT-474 cells stimulated with Jolkinolide B were significantly decreased (P < 0.01, n = 6), and the number of apoptotic cells was significantly increased (P < 0.01, n = 6). Akt and p-Akt protein levels in the two breast cancer cell lines in the Jolkinolide B group were all decreased (P < 0.01, n = 6), especially in BT-474 cells stimulated by Jolkinolide B. CONCLUSION: Jolkinolide B regulates the luminal A and luminal B subtypes of breast cancer through PI3K-Akt, EGFR and other pathways. Jolkinolide B has more significant therapeutic effect on luminal B subtype breast cancer. In vitro, experiments verified that Jolkinolide B significantly inhibited the proliferation and migration activity of BT-474 breast cancer cells by downregulating the PI3K-Akt pathway.