IgG4-associated disease with systemic lupus erythematosus: A case report and review.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Prediction of early neurologic deterioration in patients with perforating artery territory infarction using machine learning: a retrospective study.

Background: Early neurological deterioration (END) is a frequent complication in patients with perforating artery territory infarction (PAI), leading to poorer outcomes. Therefore, we aimed to apply machine learning (ML) algorithms to predict the occurrence of END in PAI and investigate related risk factors. Methods: This retrospective study analyzed a cohort of PAI patients, excluding those with severe stenosis of the parent artery. We included demographic characteristics, clinical features, laboratory data, and imaging variables. Recursive feature elimination with cross-validation (RFECV) was performed to identify critical features. Seven ML algorithms, namely logistic regression, random forest, adaptive boosting, gradient boosting decision tree, histogram-based gradient boosting, extreme gradient boosting, and category boosting, were developed to predict END in PAI patients using these critical features. We compared the accuracy of these models in predicting outcomes. Additionally, SHapley Additive exPlanations (SHAP) values were introduced to interpret the optimal model and assess the significance of input features. Results: The study enrolled 1,020 PAI patients with a mean age of 60.46 (range 49.11-71.81) years. Of these, 30.39% were women, and 129 (12.65%) experienced END. RFECV selected 13 critical features, including blood urea nitrogen (BUN), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), atrial fibrillation, loading dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), argatroban, the basal ganglia, the thalamus, the posterior choroidal arteries, maximal axial infarct diameter (measured at < 15 mm), and stroke subtype. The gradient-boosting decision tree had the highest area under the curve (0.914) among the seven ML algorithms. The SHAP analysis identified apoB as the most significant variable for END. Conclusion: Our results suggest that ML algorithms, especially the gradient-boosting decision tree, are effective in predicting the occurrence of END in PAI patients.

Mechanochemical Formation of Poly(melamine-formaldehyde) Microplastic Fibers During Abrasion of Cleaning Sponges.

The abrasion of synthetic textile fibers is a significant factor in the generation of environmental microplastic fibers (MPFs). The extent to which polymer sponges designed specifically for surface cleaning have a tendency to release MPFs during normal use remains unknown. Here, the tribological behaviors of melamine cleaning sponges (also known as "magic erasers") with different strut densities against metal surfaces of different roughness were investigated using a reciprocating abrader. The MPFs formed by sponge wear under various conditions were characterized in terms of their morphology, composition, and quantity. They were mainly composed of poly(melamine-formaldehyde) polymer with linear or branched fiber morphologies (10-405 µm in length), which were formed through deformation and fracture of the struts within open cells of the sponges, facilitated by friction-induced polymer decomposition. The rate and capability of MPF production generally increased with increasing roughness of the metal surface and density of the struts, respectively. The sponge wear could release 6.5 million MPFs/g, which could suggest a global overall emission of 4.9 trillion MPFs due to sponge consumption. Our study reveals a hitherto unrecognized source of the environmental MPF contamination and highlights the need to evaluate exposure risks associated with these new forms of MPFs.

Sensitivity-Enhancing Strategies of Graphene Field-Effect Transistor Biosensors for Biomarker Detection.

The ultrasensitive recognition of biomarkers plays a crucial role in the precise diagnosis of diseases. Graphene-based field-effect transistors (GFET) are considered the most promising devices among the next generation of biosensors. GFET biosensors possess distinct advantages, including label-free, ease of integration and operation, and the ability to directly detect biomarkers in liquid environments. This review summarized recent advances in GFET biosensors for biomarker detection, with a focus on interface functionalization. Various sensitivity-enhancing strategies have been overviewed for GFET biosensors, from the perspective of optimizing graphene synthesis and transfer methods, refinement of surface functionalization strategies for the channel layer and gate electrode, design of biorecognition elements and reduction of nonspecific adsorption. Further, this review extensively explores GFET biosensors functionalized with antibodies, aptamers, and enzymes. It delves into sensitivity-enhancing strategies employed in the detection of biomarkers for various diseases (such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious viruses, etc.) along with their application in integrated microfluidic systems. Finally, the issues and challenges in strategies for the modulation of biosensing interfaces are faced by GFET biosensors in detecting biomarkers.

Membrane-bound trehalase enhances cadmium tolerance by regulating cell apoptosis in Neocaridina denticulata sinensis.

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.

HOXD10 attenuates renal fibrosis by inhibiting NOX4-induced ferroptosis.

In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-ß1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV-HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-ß1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-ß1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Health-related quality of life in children with childhood acute myeloid leukemia in China: A five-year prospective study.

Purpose: This study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. Methods: A chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. Results: Sixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. Conclusions: This study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.

A prospective and randomized study comparing ultrasound-guided real time injection to conventional blind injection of botulinum neurotoxin for glabellar wrinkles.

BACKGROUND: Botulinum neurotoxin injections are the most frequently performed cosmetic procedures, but conventional blind injection for glabellar wrinkles remains to have some limitations. AIMS: We intend to directly inject botulinum neurotoxin into the glabella complex guided by real time ultrasound. We aim to propose a more efficient and safer botulinum neurotoxin injection strategy for glabellar wrinkles. METHODS: A total of 40 subjects with moderate to severe glabellar lines were enrolled in this study to receive botulinum neurotoxin injection, either through ultrasound-guided real time injection or conventional blind injection. Facial Wrinkle Scale (ranging from 0 = none to 3 = severe) and inter-brow distance (from 3D scanned face images) were used to evaluate the glabellar wrinkles improvement. Paired t test and two-sample t test were performed to analyze the within-group and between-group differences. RESULTS: The wrinkle score reduction was significant (p < 0.0001) immediately after the injection in ultrasound-guided injection group, but not in blind injection group (p = 0.163). Ultrasound-guided injection also showed a higher performance of wrinkle score reduction and more effective inter-brow distance increase over blind injection at Day 0 (p < 0.0001), Day 1 (p < 0.0001), Day 21 (p < 0.01) and Day 35 (p < 0.01) after initial treatment. CONCLUSIONS: The results of the study confirmed that botulinum neurotoxin injection for glabellar wrinkles under ultrasound guidance achieves quicker onset of action and better final outcomes compared to conventional blind injection.

Correlation between Mitochondria-Associated Endoplasmic Reticulum Membrane-Related Genes and Cellular Senescence-Related Genes in Osteoarthritis.

BACKGROUND: The role of mitochondria-associated endoplasmic reticulum membrane (MAM) formation in the development of osteoarthritis (OA) is yet unclear. METHODS: A mix of bioinformatics methods and in vitro experimental methodologies was used to study and corroborate the role of MAM-related genes and cellular senescence-related genes in the development of OA. The Gene Expression Omnibus database was used to obtain the microarray information that is relevant to the OA. Several bioinformatic methods were employed to carry out function enrichment analysis and protein-protein correlation analysis, build the correlation regulatory network, and investigate potential relationships between MAM-related genes and cellular senescence-related genes in OA. These methods also served to identify the MAM-related and OA-related genes (MAM-OARGs). RESULTS: For the additional functional enrichment analysis, a total of 13 MAM-OARGs were detected. The correlation regulatory network was also created. Hub MAM-OARGs were shown to have a strong correlation with genes relevant to cellular senescence in OA. Results of in vitro experiments further demonstrated a positive correlation between MAM-OARGs (PTPN1 and ITPR1) and cellular senescence-related and OA-related genes. CONCLUSIONS: As a result, our findings can offer new insights into the investigations of MAM-related genes and cellular senescence-related genes, which could be linked to the OA as well as brand-new potential treatment targets.

The distribution and antibiotic-resistant characteristics and risk factors of pathogens associated with clinical biliary tract infection in humans.

Introduction: Biliary Infection in patients is a common and important phenomenon resulting in severe complications and high morbidity, while the distributions and drug resistance profiles of biliary bacteria and related risk factors are dynamic. This study explored the characteristics of and risk factors for biliary infection to promote the rational use of antibiotics in clinically. Methods: Bacterial identification and drug susceptibility testing were completed using the Vitek 2 Compact analysis system. The distribution and antibiotic-resistant characteristics of 3,490 strains of biliary bacteria in patients at Nankai Hospital from 2019 to 2021 were analyzed using Whonet 5.6 and SPSS 26.0 software. We then retrospectively analyzed the clinical data and risk factors associated with 2,340 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (1,508 cases) and non-multidrug-resistant bacteria (832 cases) by a multivariate Cox regression model. Results and discussion: A total of 3,490 pathogenic bacterial strains were isolated from bile samples, including 2,340 (67.05%) Gram-negative strains, 1,029 (29.48%) Gram-positive strains, and 109 (4.56%) fungal strains. The top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. The rate of Escherichia coli resistance to ciprofloxacin increased (p < 0.05), while the resistance to amikacin decreased (p < 0.05). The resistance of Klebsiella pneumoniae to cephalosporins, carbapenems, ß-lactamase inhibitors, cephalases, aminoglycosides, and quinolones increased (p < 0.05), and the resistance of Pseudomonas aeruginosa to piperacillin, piperacillin/tazobactam, ticacillin/clavulanic acid, and amicacin declined significantly (p < 0.05). The resistance of Enterococcus faecium to tetracycline increased by year (p < 0.05), and the resistance of Enterococcus faecalis to erythromycin and high-concentration gentamicin declined (p < 0.05). Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for biliary infection. In summary, Gram-negative bacilli were the most common pathogenic bacteria isolated from biliary infection patients, especially Escherichia coli, and the rates and patterns of drug resistance were high and in constant flux; therefore, rational antimicrobial drug use should be carried out considering risk factors.

Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism.

Triple-negative breast cancer (TNBC) is highly malignant and lacks effective biotherapeutic targets. The development of efficient anticancer drugs with low toxicity and few side effects is a hotspot in TNBC treatment research. Although erianin is known to have potent antitumor activity, its regulatory mechanism and target in TNBC have not been fully elucidated, hampering further drug development. This study showed that erianin can significantly inhibit TNBC cell proliferation and migration, promote cell apoptosis, and inhibit the growth of transplanted tumors in mice. Mechanistically, through network pharmacology analysis, molecular docking and cellular thermal shift assays, we preliminarily identified SRC as the cellular target of erianin. Erianin potently inhibited the expression of SRC, which mediated the anticancer effect of erianin in TNBC. Moreover, erianin can downregulate the expression of genes related to cholesterol synthesis and uptake by targeting SRC, interfering with cholesterol levels in TNBC, thereby inhibiting the progression of TNBC in vivo and in vitro. Taken together, our results suggest that erianin may inhibit the progression of TNBC by suppressing SRC-mediated cholesterol metabolism, and erianin has the great potential to be an effective treatment for TNBC patients.

Insights into the effect of benzotriazoles in liver using integrated metabolomic and transcriptomic analysis.

Benzotriazoles (BTRs) are a class of benzoheterocyclic chemicals that are frequently used as metal-corrosive inhibitors, both in industry and daily use. However, the exposure effect information on BTRs remains relatively limited. In this study, an integrated metabolomic and transcriptomic approach was utilized to evaluate the effect of three BTRs, benzotriazole, 6-chloro-1-hydroxi-benzotriazole, and 1-hydroxy-benzotriazole, in the mouse liver with results showing disrupted basal metabolic processes and vitamin and cofactor metabolism after 28 days. The expression of several genes that are related to the inflammatory response and aryl hydrocarbon receptor pathways, such as Gstt2 and Arntl, was altered by the exposure to BTRs. Exposure to BTRs also affected metabolites and genes that are involved in the immune system and xenobiotic responses. The altered expression of several cytochrome P450 family genes reveal a potential detoxification mechanism in the mouse liver. Taken together, our findings provide new insights into the multilayer response of the mouse liver to BTRs exposure as well as a resource for further exploration of the molecular mechanisms by which the response occurs.

Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB.

BACKGROUND: While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. METHODS: We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. RESULTS: Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. CONCLUSIONS: Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment.

Evaluation of droplet digital PCR by detecting cell-free DNA in pleural effusion for the diagnosis of tuberculous pleurisy: a multicenter cohort study.

OBJECTIVES: Tuberculous pleurisy is one of the most common extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicenter cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing Tuberculous pleurisy. METHODS: Patients with suspected tuberculosis (≥ 5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR and cf-ddPCR were performed simultaneously for all specimens. RESULTS: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite Tuberculous pleurisy, 113 possible Tuberculous pleurisy and 63 non-Tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI = 82.8% to 95.1%) in the definite Tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI = 47.1% to 66.6%, P<0.001), Xpert (46.7%, 49/105, 95% CI = 37.0% to 56.6%, P<0.001), Ultra (69.5%, 73/105, 95% CI = 59.7% to 77.9%, P<0.001) and real-time PCR (75.2%, 79/105, 95% CI: 65.7% to 82.9%, P < 0.001). In possible Tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI = 51.4% to 70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI = 19.7% to 36.8%, P<0.001) and real-time PCR (38.9%, 44/113, 95% CI: 30.0% to 48.6%, P < 0.001). CONCLUSIONS: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.

Schistosoma japonicum extracellular vesicle proteins serve as effective biomarkers for diagnosing parasite infection.

Schistosoma species are the causative agent of schistosomiasis and shows worldwide distribution. There is a great need to develop a sensitive diagnostic approach for controlling the disease. Previously, we identified large numbers of Extracellular Vesicle (EV) proteins from Schistosoma japonicum (S. japonicum), but rarely these proteins have been evaluated for their diagnostic potential. In the present study, we performed bioinformatic analyses of S. japonicum identified EV-associated proteins from the previous study and then identified Schistosoma-specific proteins with potentially secreted capability. Among them, we selected SJCHGC02838 protein, SJCHGC05593 protein, SJCHGC05668 protein and a hypothetical protein (SJHYP) to evaluate their diagnostic potential for detecting S. japonicum infection. First, we determined the expression of these four proteins at the transcript levels using qRT-PCR and revealed that all these genes showed higher expression in adult stage. Then, we cloned the full-length cDNA for each protein into a prokaryotic expression vector and successfully generated the recombinant proteins. Upon the purification of recombinant proteins, we developed an indirect ELISA method to evaluate the diagnostic potential of these purified recombinant proteins. The results showed high sensitivity for detecting Schistosoma infection. Additionally, these proteins also displayed a good potential for detecting Schistosoma infection, especially SJCHGC05668 protein at an early stage. The diagnostic potentials of these recombinant proteins were further evaluated by Western blot and comparatively analyzed by our previously developed cfDNA methods.

Ternary Eu3+ crystalline complexes with photoluminescence and triboluminescence for dynamic stress visualization.

Investigation of photoluminescence (PL) and fracture-induced triboluminescence (TL) is necessary for the development of both fundamental theories and practical applications in mechanical energy conversion; however, most known PL/TL-emitting materials are confined to inorganic systems. In this study, a novel lanthanide-based crystalline complex (LnCC), Eu(DBM)3DETA was synthesized via the synergistic coordination of Eu3+ with DBM (Dibenzoylmethane) and DETA (Diethylenetriamine) units, leading to the formation of brighter LnCC with bright red emission, high PL quantum yields (57.19 %) and unique TL characteristics. The key to success in obtaining Eu(DBM)3DETA is the utilization of DETA molecule as synergistic ligand, presenting block crystals with higher coordination number of Eu3+ ions via recrystallization. Due to the dense accumulation of cross-linked three-dimensional frameworks through van der Waals interactions, the fracture-induced piezoelectric effect results in charge separation and excitation through the resultant electric field and discharge, triggering a fast TL response of Eu(DBM)3DETA and expanding the possibilities of the quantitative stress sensing. Importantly, amorphous powders can still recover to their original PL and TL emission intensities after recrystallization in cyclic crystal-to-amorphous phase transitions. The unique PL and TL characteristics of Eu(DBM)3DETA provide promising opportunities to display stress visualization differences of electronic signatures under different forces.

Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.

To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through a structural optimization strategy, and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by the MTT assay. Some of these compounds exhibited excellent inhibitory activity against three different cancer cell lines. Compounds 6a, 8i, and 13a showed better antiproliferative activity against K562 cells, with IC50 values of 3871.5, 613.6 and 134.7 nM, respectively, than did paclitaxel (35.6 nM), doxorubicin (2689.0 nM), and NSC 617145 (20.3 nM). To further verify whether the antiproliferative activity of these compounds is dependent on WRN, PC3 cells overexpressing WRN (PC3-WRN) were constructed to further study their antiproliferative potency in vitro, and the inhibition ratio and IC20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than were the control group cells (PC3-NC). The IC20 ratios of compounds 6a, 8i, and 13a to PC3-NC and PC3-WRN were 94.3, 153.4 and 505.5, respectively. According to the docking results, the compounds 6a, 8i, and 13a overlapped well with the binding pocket of 6YHR. Further study demonstrated that among the tested compounds, 13a was the most sensitive to PC3-WRN. In summary, our research identified a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents.

Integrated influence of sulfide modification on the reactivity of nanoscale zero-valent iron towards decabromodiphenyl ether under an electromagnetic field.

Individual application of sulfide modification and electromagnetic field (EMF) can enhance the reactivity of nanoscale zero-valent iron (nZVI), yet the potential of both in combination is not clear. This work found that the reactivity of nZVI towards decabromodiphenyl ether was significantly enhanced by the combined effect of sulfidation and EMF. The specific reaction rate constant of nZVI increased by 7 to 10 times. A series of characterization results revealed that the sulfidation level not only affects the inherent reactivity but also the magnetic-induced heating (MIH) and corrosion (MIC) of nZVI. These collectively influence the degradation efficiency of nZVI under EMF. Sulfidation generally diminished the MIH effect. The low degree of sulfidation (S/Fe = 0.1) slightly reduced the MIC effect by 21.4%. However, the high degree of sulfidation (S/Fe = 0.4) led to significantly enhanced MIC effect by 107.1%. For S/Fe = 0.1 and 0.4, the overall enhancement in the reactivity resulting from EMF was alternately dominated by the contributions of MIH and MIC. This work provides valuable insights into the MIH and MIC effects about the sulfidation level of nZVI, which is needed for further exploration and optimization of this combined technology.

Vaginal micro-environment disorder promotes malignant prognosis of low-grade cervical intraepithelial neoplasia: a prospective community cohort study in Shanxi Province, China.

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

[Retracted] Tissue­specific transplantation antigen P35B functions as an oncogene and is regulated by microRNA­125a­5p in lung cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 1A on p. 5, colony formation data shown in Figs. 2C, H and M and 6D on p. 6 and p. 10 respectively, the western blots in Fig. 2B, Transwell cell migration and invasion assay data in Fig. 3B, D and F, and immunofluorescence data in Fig. 4C had already appeared in previously published articles written by different authors at different research institutes (some of which have subsequently been retracted). Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 72, 2021; DOI: 10.3892/or.2021.8023].