Time-dependent nonmonotonic concentration-response and synergism of alkyl glycosides with different alkyl side chain to Vibrio qinghaiensis sp. -Q67.

Alkyl glycosides (AGs), commonly used nonionic surfactants, may have toxic effects on the environmental organisms. However, the complex concentration-response patterns of AGs with varying alkyl side chains and their mixtures have not been thoroughly studied. Therefore, the luminescence inhibition toxicities of six AGs with different alkyl side chains, namely, ethyl (AG02), butyl (AG04), hexyl (AG06), octyl (AG08), decyl (AG10), and dodecyl (AG12) glucosides, were determined in Vibrio qinghaiensis sp. -Q67 (Q67) at 0.25, 3, 6, 9, and 12 h. The six AGs exhibited time- and side-chain-dependent nonmonotonic concentration- responses toward Q67. AG02, with a short side chain, presented a concentration-response curve (CRC) with two peaks after 6 h and stimulated the luminescence of Q67 at both 6 and 9 h. AG04, AG06, and AG08 showed S-shaped CRCs at five exposure time points, and their toxicities increased with the side-chain length. AG10 and AG12, with long side chains, exhibited hormesis at 9 and 12 h. Molecular docking was performed to explore the mechanism governing the possible influence of AGs on the luminescence response. The effects of AGs on Q67 could be attributed to multiple luminescence-regulatory proteins, including LuxA, LuxC, LuxD, LuxG, LuxI, and LuxR. Notably, LuxR was identified as the primary binding protein among the six AGs. Given that they may co-exist, binary mixtures of AG10 and AG12 were designed to explore their concentration-response patterns and interactions. The results revealed that all AG10-AG12 binary mixture rays showed time-dependent hormesis on Q67, similar to that shown by their individual components. The interactions of these binary mixtures were mainly characterized by low-concentration additive action and high-concentration synergism at different times.

Influential factors on urine EV DNA methylation detection and its diagnostic potential in prostate cancer.

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers.

A new proposal for phenotypic classification and outcome assessment of dermatomyositis based on clinical manifestations and serological testing.

BACKGROUND: Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes clinical diagnosis and treatment of DM very challenging. OBJECTIVES: Unsupervised classification in DM patients and analysis of key factors related to clinical outcomes. METHODS: This retrospective study was conducted between 2017 and 2022 at the Department of Rheumatology, Xiangya Hospital, Central South University. 162 DM patients were enrolled for unsupervised hierarchical cluster analysis. In addition, we divided the clinical outcomes of DM patients into four subgroups: withdrawal, stabilization, aggravation, and death, and compared the clinical profiles amongst the subgroups. RESULTS: Out of 162 DM patients, three clusters were defined. Cluster 1 (n = 40) was mainly grouped by patients with prominent muscular involvement and mild Interstitial Lung Disease (ILD). Cluster 2 (n = 72) grouped patients with skin rash, anti-Melanoma Differentiation Associated protein 5 positive (anti-MDA5+), and Rapid Progressive Interstitial Lung Disease (RP-ILD). Cluster 3 (n = 50) grouped patients with the mildest symptoms. The proportion of death increased across the three clusters (cluster 3 < cluster 1 < cluster 2). STUDY LIMITATIONS: The number of cases was limited for the subsequent construction and validation of predictive models. We did not review all skin symptoms or pathological changes in detail. CONCLUSIONS: We reclassified DM into three clusters with different risks for poor outcome based on diverse clinical profiles. Clinical serological testing and cluster analysis are necessary to help clinicians evaluate patients during follow-up and conduct phenotype-based personalized care in DM.

Metabolic profiling in tissues and urine of patients with prostatic lesions and the diagnostic value of urine extracellular vesicles metabolites in prostate cancer.

BACKGROUND: Prostate cancer (PCa) lacks convenient and highly specific diagnostic markers. Although the value of extracellular vesicles (EV) in oncology is widely recognized, the diagnostic value of EV metabolites requires further exploration. This study aimed to explore the diagnostic value of urine EV (u-EV) metabolomics in PCa. METHODS: We first detected metabolites in paired tissues cells (cells), tissue EV (t-EVs), u-EVs, and urine samples in cohort 1 (8 PCa vs. 5 benign prostatic hypertrophy, BPH) to prob the feasibility of EV metabolites as diagnostic markers. We then analyzed the value of u-EVs as markers for PCa diagnosis and typing in the expanded sample cohort (60 PCa vs. 40 BPH). RESULTS: U-EV metabolites were more consistent with those in tissue-derived samples (cells and t-EVs) than those in urine, and more differential metabolites between BPH and PCa were identified in u-EV. Subsequently, we used a random forest model to construct a panel of six metabolites for PCa, which showed an area under the curve (AUC) of 0.833 in training cohort and 0.844 in validation cohort. We also found significantly differentially expressed metabolites between PCa subtypes (Gleason ≤ 7 vs. Gleason > 7 and localized vs. metastasis), demonstrating the value of EV metabolites in PCa typing and prognostic assessment. CONCLUSION: Metabolomic analysis of u-EVs is a promising source of noninvasive markers for PCa diagnosis.

Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures.

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data. Five high-frequency components (HFCs), betaine (BET), 1,3-butanediol (BUT), ethylenediaminetetraacetic acid disodium salt (EDTA), glycerol (GLO), and phenoxyethanol (POE), and 14 mixtures were identified. For each mixture system, one mixture ray with the actual mixture ratios in the products was selected. Time-dependent microplate toxicity analysis was used to test the luminescence inhibition toxicity of five HFCs and 14 mixture rays to Vibrio qinghaiensis sp.-Q67 at 12 concentration gradients and eight exposure times. It is showed that BET, EDTA, POE, and 13 mixture rays containing at least one J-type component showed time-dependent hormesis. Characteristic parameters used to describe hormesis revealed that the absolute value of the maximum stimulatory effect (|Emin|) generally increased with time. Notably, mixtures composed of POE and S-type components showed greater |Emin| than POE alone at the same time. Importantly, the maximum stimulatory effective concentration, NOEC/the zero effective concentration point, and EC50 remained relatively stable. Nine hormesis transmission phenomena were observed in different mixture rays. While all mixtures primarily exhibited additive action, varying degrees of synergism and antagonism were noted in binary mixtures, with no strong synergism or antagonism observed in ternary and quaternary mixtures. These findings offer valuable insights for the screening of HFCs and their mixtures, as well as the study of hormesis transmission in personal care products.

Effect of waiting time for radiotherapy after last induction chemotherapy on prognosis of locally advanced nasopharyngeal carcinoma.

BACKGROUND: The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. METHODS: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. RESULTS: The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003-1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57-4.6), OS (HR = 2.55; 95%CI: 1.29-5.03), DMFS (HR = 3.07; 95%CI: 1.64-5.76) and LRFS (HR = 2.26; 95%CI: 1.21-4.21). CONCLUSION: The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.

Comparative effectiveness and safety of inhaled corticosteroid plus long-acting ß2-agonist fixed-dose combinations vs. long-acting muscarinic antagonist in bronchiectasis.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in bronchiectasis. RESEARCH DESIGN AND METHODS: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. RESULTS: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL. CONCLUSION: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.

Andrographolide inhibits Burkitt's lymphoma by binding JUN and CASP3 proteins.

BACKGROUND: Burkitt's lymphoma, one of the most common subtypes of pediatric malignant lymphoma, is notorious for its swift onset, aggressive proliferation, pronounced invasiveness, and marked malignancy. The therapeutic landscape for Burkitt's lymphoma currently falls short of providing universally effective and tolerable solutions. Andrographolide, a primary active component of Andrographis paniculata, is renowned for its properties of heat-clearing, detoxification, inflammation reduction, and pain relief. It is predominantly used in treating bacterial and viral infections of the upper respiratory tract, as well as dysentery. Various reports highlight the antitumor effects of andrographolide. Yet, its specific impact and the underlying mechanism of action on Burkitt's lymphoma remain an uncharted area of research. METHOD: We employed network pharmacology to pinpoint the targets of andrographolide's action on Burkitt's lymphoma and the associated pathways. We then evaluated the impact of andrographolide on Burkitt's lymphoma using both in vitro and in vivo patient-derived xenograft (PDX) models. Concurrently, we confirmed the molecular targets of andrographolide in Burkitt's lymphoma through immunofluorescence assays. RESULT: Utilizing network pharmacology, we identified 15 relevant targets, 60 interrelationships between these targets, and numerous associated signaling pathways for andrographolide's action on Burkitt's lymphoma. In vitro efficacy tests using High-throughput Drug Sensitivity Testing and in vivo PDX model evaluations revealed that andrographolide effectively curtailed the growth of Burkitt's lymphoma. Moreover, we observed a increased in the expression of JUN (c-Jun) and CASP3 (Caspase 3) proteins in Burkitt's lymphoma cells treated with andrographolide. CONCLUSION: Andrographolide inhibits the growth of Burkitt's lymphoma by inhibiting JUN and CASP3 proteins.

Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6.

BACKGROUND: Multiple myeloma (MM) is a common hematological malignancy. Drug resistance remains to be a major clinical challenge in MM therapy. In this study, we aim to investigate the functional roles of bone marrow mesenchymal stem cells (BMSC)-derived exosomal miR-182 on the carfilzomib resistance of MM and its underlying mechanism. METHODS: qRT-PCR and Western blot methods were utilized to confirm the gene or protein expressions. CCK-8 and transwell assays were performed to measure the capabilities of proliferation, migration, and invasion. The molecular interactions were validated through ChIP and Dual luciferase assay. RESULTS: Our findings indicated that miR-182 expression was upregulated in serum, BMSCs and BMSC-derived exosomes from MM patients. Hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor in tumor microenvironment, could boost miR-182 expression by directly binding to its promoter, thus favoring exosomal secretion. Moreover, exosomal miR-182 from BMSCs could be transferred to MM cells and was able to promote malignant proliferation, metastasis, and invasion, as well as decrease the sensitivity of MM cells against carfilzomib. Additionally, SOX6 was identified as a downstream target of miR-182 in MM cells, and its expression was negatively regulated by miR-182. Rescue experiments proved that loss of SOX6 in MM cells dramatically reversed the promoting roles of BMSC-secreted exosomal miR-182 on proliferation, metastasis, and carfilzomib resistance in MM cells. CONCLUSION: Collectively, our findings indicated that exosomal miR-182 derived from BMSCs contributed to the metastasis and carfilzomib resistance of MM cells by targeting SOX6. This study sheds light on the pathogenesis of the BMSC-derived exosome containing miR-182 in the malignant behaviors of MM cells and carfzomib resistance.

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

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

Reoperation after surgical treatment for benign prostatic hyperplasia: a systematic review.

Context: Surgical treatment is important for male lower urinary tract symptom (LUTS) management, but there are few reviews of the risks of reoperation. Objective: To systematically evaluate the current evidence regarding the reoperation rates of surgical treatment for LUTS in accordance with current recommendations and guidelines. Evidence acquisition: Eligible studies published up to July 2023, were searched for in the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases. STATA® (StataCorp LP, College Station, TX, USA) software was used to conduct the meta-analysis. Random-effects models were used to calculate the pooled incidences (PIs) of reoperation and the 95% confidence intervals (CIs). Evidence synthesis: A total of 119 studies with 130,106 patients were included. The reoperation rate of transurethral resection of the prostate (TURP) at 1, 2, 3, and 5 years was 4.0%, 5.0%, 6.0%, and 7.7%, respectively. The reoperation rate of plasma kinetic loop resection of the prostate (PKRP) at 1, 2, 3, and 5 years was 3.5%, 3.6%, 5.7%, and 6.6%, respectively. The reoperation rate of holmium laser enucleation of the prostate (HoLEP) at 1, 2, 3, and 5 years was 2.4%, 3.3%, 5.4%, and 6.6%, respectively. The reoperation rate of photoselective vaporization of the prostate (PVP) at 1, 2, 3, and 5 years was 3.3%, 4.1%, 6.7%, and 7.1%, respectively. The reoperation rate of surgery with AquaBeam® at 1, 2, 3, and 5 years was 2.6%, 3.1%, 3.0%, and 4.1%, respectively. The reoperation rate of prostatic artery embolization (PAE) at 1, 2, 3, and 5 years was 12.2%, 20.0%, 26.4%, and 23.8%, respectively. The reoperation rate of transurethral microwave thermotherapy (TUMT) at 1, 2, 3, and 5 years was 9.9%, 19.9%, 23.3%, and 31.2%, respectively. The reoperation rate of transurethral incision of the prostate (TUIP) at 5 years was 13.4%. The reoperation rate of open prostatectomy (OP) at 1 and 5 years was 1.3% and 4.4%, respectively. The reoperation rate of thulium laser enucleation of the prostate (ThuLEP) at 1, 2, and 5 years was 3.7%, 7.7%, and 8.4%, respectively. Conclusion: Our results summarized the reoperation rates of 10 surgical procedures over follow-up durations of 1, 2, 3, and 5 years, which could provide reference for urologists and LUTS patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445780.

Beneficial or harmful: Time-dependent hormesis induced by typical disinfectants and their mixtures with toxicological interaction.

Disinfectants and their mixtures can induce hormesis. However, how the mixture hormesis is related to those of components and the interactions in disinfectant mixtures remain unclear. In this paper, the luminescence inhibition toxicities of chlorinated sodium phosphate (CSP), dodecyl dimethyl benzyl ammonium bromide (DOB), dodecyl dimethyl benzyl ammonium chloride (DOC), ethanol (EtOH), glutaraldehyde (GLA), hydrogen peroxide (H2O2), isopropyl alcohol (IPA), n-propanol (NPA), and 20 mixture rays in four mixture systems (EtOH-H2O2, DOB-H2O2, DOC-EtOH, and EtOH-IPA-NPA) containing at least one component showing hormesis to Vibrio qinghaiensis sp.-Q67 (Q67) were determined at 0.25, 3, 6, 9, and 12 h. The synergism-antagonism heatmap based on independent action model (noted as SAHmapIA) was developed to systematically evaluate the interactions in various mixtures. It was shown that five disinfectants (CSP, EtOH, H2O2, NPA, and IPA) and 17 mixture rays exhibited time-dependent hormesis. The hormetic component was responsible for the hormesis of the mixture rays. Most mixture rays showed low- concentration/dose additive action and high-concentration/dose synergism at different time. This study further exemplified the interrelationship between the hormesis in the mixtures and their components and implied the need to pay attention to the time-dependent hormesis and interactions induced by the disinfectants.

Effects of neuraxial labor analgesia on intrapartum maternal fever in full-term pregnancy and its influence on birth outcomes.

Introduction: This study aimed to explore the relationship between neuraxial labor analgesia and intrapartum fever and to demonstrate the influence of maternal fever on perinatal outcomes within 6 weeks after birth. Methods: This was a secondary analysis of a multicenter prospective cohort study that enrolled women with single- and full-term cephalic pregnancy in northern China. Intrapartum maternal fever was defined as the highest axillary temperature during labor ≥37.5°C. Data on baseline characteristics, maternal variables, and neonatal outcomes were all collected. The association between neuraxial labor analgesia and intrapartum maternal fever was analyzed with logistic regression models, and the cutoff point was identified by the receiver operating characteristic curve. Results: Of 577 parturients, 74 (12.8%) developed intrapartum fever. Neuraxial analgesia was associated with an increased risk of maternal intrapartum fever with or without adjusting for confounding factors (adjusted OR = 2.68; 95% CI: 1.32-5.47; p = 0.007). Further analysis showed that neuraxial analgesia of <5 h did not increase the risk of intrapartum fever compared with no analgesia (OR = 1.52; 95% CI: 0.63-3.64; p = 0.35), and longer neuraxial labor analgesia time (over 5 h) significantly increased the risk of fever (OR = 3.38; 95% CI: 1.63-7.01; p = 0.001). Parturients with intrapartum fever suffered more maternal adverse outcomes compared with those without fever (p < 0.001). Neonates of women with intrapartum fever had slightly higher rates of composite adverse neonatal outcomes compared with those without fever; however, the difference was not statistically significant (p = 0.098). Conclusion: In women with low-risk pregnancies, a longer time of neuraxial labor analgesia was associated with an increased risk of intrapartum maternal fever. Intrapartum fever was related to adverse maternal outcomes but did not significantly affect neonatal outcomes within 6 weeks after delivery.

Comparative Transcriptome Analysis Reveals the Molecular Basis of Brassica napus in Response to Aphid Stress.

Rapeseed is a globally important economic crop that can be severely impacted by aphids. However, our understanding of rapeseed resistance to aphid stress is very limited. In this study, we analyzed the resistance characteristics of the low aphid-susceptible variety APL01 and the highly aphid-susceptible variety Holly in response to aphid stress. APL01 had a more significant inhibitory effect on aphid proliferation compared with Holly during the early stage of inoculation, whereas Holly showed stronger tolerance to aphid stress compared with APL01 during the later stage of inoculation. Through transcriptome, physiological, and gene expression analyses, it was revealed that chitinase activity, catalase activity, calcium signal transduction, and activation of systemic acquired resistance might be involved in aphid resistance in B. napus. The degree of inhibition of photosynthesis in plants under aphid stress directly determines the tolerance of B. napus to aphid stress. Furthermore, four promising candidate genes were screened from eight genes related to rapeseed response to biotic stress through RT-qPCR analysis of gene expression levels. These research findings represent an important step forward in understanding the resistance of rapeseed to aphid stress and provide a solid foundation for the cloning of genes responsible for this resistance.

Analysis of the genetic contribution to thoracic aortic aneurysm or dissection in a prospective cohort of patients with familial and sporadic cases in East China.

BACKGROUND: Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel. RESULTS: A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk. CONCLUSIONS: TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.

Time-dependent hormetic dose responses of skin care product mixtures to Vibrio qinghaiensis sp.-Q67: Appearance and quantification.

Hormesis is a widely recognized and extensively studied phenomenon. However, few studies have described the quantitative characteristics of hormesis required for appropriate risk assessment. Although skin care product (SCP) mixtures and their active ingredients can induce the hormesis of Vibrio qinghaiensis sp.-Q67 (Q67), the quantitative characteristics of time-dependent hormetic dose responses in SCPs have not yet been investigated. In this study, 28 SCP mixtures were tested for luminescence toxicity against Q67 after five exposure durations (0.25, 3, 6, 9, and 12 h). With increasing exposure duration, the concentration response curves (CRCs) were classified as constant monotonic nonlinear (S-shaped) for four SCPs, S- to hormetic (J-shaped) for 13 SCPs, and constant J-shaped for 11 SCPs. Of 140 CRCs, 98 were J-shaped. An increased frequency of SCPs inducing hormesis was observed. The toxicity (pEC50) of the SCPs was independent of the exposure duration and product type. The maximum stimulatory effect (Emin) of the 12 SCPs increased with exposure duration. We proposed a modified parameter, the width of inhibition dose zone (WIDZ; EC50/EC10), to depict the width of inhibition dose zone. The WIDZ of S-shaped CRCs were significantly larger than that of J-shaped CRCs. In addition, the characteristic parameters reported in the general literature were analyzed. The good linear relationship between EC50 and the maximum stimulatory effective concentration (ECmin) indicated that toxicity may be transformed into stimulatory effects over exposure durations. The width of stimulation dose zone (WSDZ) and Emin of the seven SCPs had the same increasing trends with increasing exposure duration. The combination of WIDZ with other characteristic parameters (e.g., zero effective concentration point, ECmin, etc.) could better depict hormesis with low-dose stimulation and high-dose inhibition. The quantitative characteristics of the dose-responses of hormesis-inducing SCPs could provide reference basis for the risk assessment of SCP mixtures.

Update on poly(ADP-ribose) polymerase inhibitors resistance in ovarian cancer.

Ovarian cancer is one of the most common reproductive system tumors. The incidence of ovarian cancer in China is on the rise. Poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) is a DNA repair enzyme associated with DNA damage repair. PARPi takes PARP as a target to kill tumor cells, especially for tumors with homologous recombination (HR) dysfunction. Currently, PARPi has been widely used in clinical practice, mainly for the maintenance of advanced ovarian epithelial cancer. The intrinsic or acquired drug resistance of PARPi has gradually become an important clinical problem with the wide application of PARPi. This review summarizes the mechanisms of PARPi resistance and the current progress on PARPi-based combination strategies.

Tumor-derived extracellular vesicle nucleic acids as promising diagnostic biomarkers for prostate cancer.

Liquid biopsy as a non-invasive method has a bright future in cancer diagnosis. Tumor-related extracellular vesicles (EVs) and their components (nucleic acids, proteins, and lipids) in biofluids may exert multiple functions in tumor growth, metastasis, immune escape, and angiogenesis. Among all the components, nucleic acids have attracted the most interest due to their simplicity of extraction and detection. In this review, the biological functions of EVs in prostate cancer (PCa) genesis and progression were summarized. Moreover, the diagnostic value of EV RNA markers found in clinical body fluid samples was reviewed, including their trends, challenging isolation methods, and diagnostic efficacy. Lastly, because relatively much progress has been made in PCa, studies on EV DNA markers are also discussed.

Optimized Derivation of Predicted No-Effect Concentrations (PNECs) for Eight Polycyclic Aromatic Hydrocarbons (PAHs) Using HC10 Based on Acute Toxicity Data.

For persistent organic pollutants, a concern of environmental supervision, predicted no-effect concentrations (PNECs) are often used in ecological risk assessment, which is commonly derived from the hazardous concentration of 5% (HC5) of the species sensitivity distribution (SSD). To address the problem of a lack of toxicity data, the objectives of this study are to propose and apply two improvement ideas for SSD application, taking polycyclic aromatic hydrocarbons (PAHs) as an example: whether the chronic PNEC can be derived from the acute SSD curve; whether the PNEC may be calculated by HC10 to avoid solely statistical extrapolation. In this study, the acute SSD curves for eight PAHs and the chronic SSD curves for three PAHs were constructed. The quantity relationship of HC5s between the acute and chronic SSD curves was explored, and the value of the assessment factor when using HC10 to calculate PNEC was derived. The results showed that, for PAHs, the chronic PNEC can be estimated by multiplying the acute PNEC by 0.1, and the value of the assessment factor corresponding to HC10 is 10. For acenaphthene, anthracene, benzo[a]pyrene, fluoranthene, fluorene, naphthalene, phenanthrene, and pyrene, the chronic PNECs based on the acute HC10s were 0.8120, 0.008925, 0.005202, 0.07602, 2.328, 12.75, 0.5731, and 0.05360 µg/L, respectively.