Russell Mechanism-Mediated Cancer Therapy: A Minireview.

The Russell mechanism, proposed by Russell, is a cyclic mechanism for the formation of linear tetroxide intermediates, which can spontaneously produce cytotoxic singlet oxygen (1O2) independent of oxygen, suggesting its anticancer potential. Compared with other mainstream anticancer strategies, the Russell mechanism employed for killing cancer cells does not require external energy input, harsh pH condition, and sufficient oxygen. However, up till now, the applications of Russell mechanism in antitumor therapy have been relatively rare, and there is almost no summary of the Russell mechanism in the cancer therapy field. This minireview introduces the different metal elements-based Russell mechanisms and the relevant research progress in Russell mechanism-based cancer therapy in recent years. At the same time, we briefly discussed the current challenges and future development regarding the applications of Russell mechanism. It is hoped that this review can further expand the research of Russell Mechanism in the biomedical field, and inspire researchers to extend its application fields to antibacterial, antiinflammatory, and wound healing uses.

A new strategy for accelerating recovery of anaerobic granular sludge after low-temperature shock: In situ regulation of quorum sensing microorganisms embedded in polyvinyl alcohol sodium alginate.

Low-temperature could inhibit the performance of anaerobic granular sludge (AnGS). Quorum sensing (QS), as a communication mode between microorganisms, can effectively regulate AnGS. In this study, a kind of embedded particles (PVA/SA@Serratia) based on signal molecule secreting bacteria was prepared by microbial immobilization technology based on polyvinyl alcohol and sodium alginate to accelerate the recovery of AnGS system after low temperature. Low-temperature shock experiment verified the positive effect of PVA/SA@Serratia on restoring the COD removal rate and methanogenesis capacity of AnGS. Further analysis by metagenomics analysis showed that PVA/SA@Serratia stimulated higher QS activity and promoted the secretion of extracellular polymeric substance (EPS) in AnGS. The rapid construction of EPS protective layer effectively accelerated the establishment of a robust microbial community structure. PVA/SA@Serratia also enhanced multiple methanogenic pathways, including direct interspecies electron transfer. In conclusion, this study demonstrated that PVA/SA@Serratia could effectively strengthen AnGS after low-temperature shock.

Roles of reactive oxygen species in inflammation and cancer.

Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.

Effects of Dexamethasone on Postoperative Glycemic Control in Patients After Primary Total Joint Arthroplasty: A Randomized Double-Blind Controlled Trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the use of dexamethasone (DEX) may cause perioperative blood glucose (BG) disorders, leading to complications even in patients who do not have diabetes. We aimed to evaluate the effects of different DEX doses on perioperative BG levels. METHODS: A total of 135 patients who do not have diabetes were randomized into three groups: preoperative intravenous injection of normal saline (Group A, the placebo group), preoperative intravenous injection of 10 mg DEX (Group B), and preoperative intravenous injection of 20 mg DEX (Group C). Postoperative fasting blood glucose (FBG) levels were designated as the primary outcome, while postoperative postprandial blood glucose (PBG) levels were assigned as the secondary outcome. The incidence of complications was recorded. We also investigated the risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. RESULTS: The FBG levels were higher in Groups B and C than in Group A on postoperative days (POD) 0 and 1. The PBG levels were lower for Groups A and B compared to Group C on POD 1. No differences in FBG or PBG were detected beyond POD 1. Elevated preoperative glycosylated hemoglobin A1c (HbA1c) levels increased the risk of FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl, respectively. However, preoperative intravenous injection of DEX was not associated with FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. No differences were found in postoperative complications among the three groups. CONCLUSION: The preoperative intravenous administration of 10 or 20 mg DEX in patients who do not have diabetes showed transient effects on postoperative BG after TJA. The preoperative HbA1c level threshold (regardless of the administration or dosage of DEX) that increased the risk for the occurrence of FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl was 5.75% and 5.85%, respectively.

A fully validated LC­MS/MS method for quantifying bevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.

Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.

Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response.

The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate antitumor immunity, herein a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) is rationally designed containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic Cip-OH and chemotherapeutic drug CPT are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment.

Structure and composition of dissolved organic matters in sludge by ultrasonic treatment.

The leaching of dissolved organic matter (DOM) from the sludge into the liquid phase is induced by ultrasound. However, there is limited investigation into the structure and molecular composition of sludge DOM in this process. The molecular structure and composition of sludge DOM in ultrasonic treatment were comprehensively elucidated in this study. The sludge dissolved organic carbon (DOC) and three-dimensional fluorescence spectroscopy (3D-EEM) image had most significant change at 15-min ultrasonic time and 1.2 W/mL ultrasonic density, respectively. Gas Chromatography-Mass Spectrometry (GC-MS) analysis indicated that ultrasonic treatment of sludge reduced the macromolecules to small molecules in DOM. Then, electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS) analysis revealed that lignin, tannins, and carbohydrates were the main components of sludge DOMs after ultrasound treatment. analysis revealed that lignin, tannins, and carbohydrates were the main components of sludge DOMs after ultrasound treatment. Furthermore, through the Van Krevelen analysis, the major components were CHO (48.50%) and CHOS (23.20%) in the DOM of ultrasonicated sludge. This research provides the basis for the practical application of ultrasonic treatment of sludge and provides basic information for DOM components.

Major influencing factors identification and probabilistic health risk assessment of soil potentially toxic elements pollution in coal and metal mines across China: A systematic review.

Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.

ß-Galactosidase-activated near-infrared AIEgen for ovarian cancer imaging in vivo.

Near-infrared (NIR) aggregation induced-emission luminogens (AIEgens) circumvent the noisome aggregation-caused quenching (ACQ) effect in physiological milieu, thus holding high promise for real-time and sensitive imaging of biomarkers in vivo. ß-Galactosidase (ß-Gal) is a biomarker for primary ovarian carcinoma, but current AIEgens for ß-Gal sensing display emissions in the visible region and have not been applied in vivo. We herein propose an NIR AIEgen QM-TPA-Gal and applied it for imaging ß-Gal activity in vitro and in ovarian tumor model. After being internalized by ovarian cancer cells (e.g., SKOV3), the hydrophilic nonfluorescent QM-TPA-Gal undergoes hydrolyzation by ß-Gal to yield hydrophobic QM-TPA-OH, which subsequently aggregates into nanoparticles to turn NIR fluorescence "on" through the AIE mechanism. In vitro experimental results indicate that QM-TPA-Gal has a sensitive and selective response to ß-Gal with a limit of detection (LOD) of 0.21 U/mL. Molecular docking simulation confirms that QM-TPA-Gal has a good binding ability with ß-Gal to allow efficient hydrolysis. Furthermore, QM-TPA-Gal is successfully applied for ß-Gal imaging in SKOV3 cell and SKOV3-bearing living mouse models. It is anticipated that QM-TPA-Gal could be applied for early diagnosis of ovarian cancers or other ß-Gal-associated diseases in near future.

Comprehensive carbon footprint analysis of wastewater treatment: A case study of modified cyclic activated sludge technology for low carbon source urban wastewater treatment.

To reduce pollution and carbon emissions, a quantitative evaluation of the carbon footprint of the wastewater treatment processes is crucial. However, micro carbon element flow analysis is rarely focused considering treatment efficiency of different technology. In this research, a comprehensive carbon footprint analysis is established under the micro carbon element flow analysis and macro carbon footprint analysis based on life cycle assessment (LCA). Three wastewater treatment processes (i.e., anaerobic anoxic oxic, A2O; cyclic activated sludge technology, CAST; modified cyclic activated sludge technology, M-CAST) for low carbon source urban wastewater are selected. The micro key element flow analysis illustrated that carbon source mainly flows to the assimilation function to promote microorganism growth. The carbon footprint analysis illustrated that M-CAST as the optimal wastewater treatment process had the lowest global warming potential (GWP). The key to reduce carbon emissions is to limit electricity consumption in wastewater treatment processes. Under the comprehensive carbon footprint analysis, M-CAST has the lowest environmental impact with low carbon emissions. The sensitivity analysis results revealed that biotreatment section variables considerably reduced the environmental impact on the LCA and the GWP, followed by the sludge disposal section. With this research, the optimization scheme can guide wastewater treatment plants to optimize relevant treatment sections and reduce pollution and carbon emissions.

Misdiagnosis of synovial sarcoma - cellular myofibroma with SRF-RELA gene fusion: A case report.

BACKGROUND: Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017. Its diagnosis is often challenging because of its relative rarity, lack of known genetic abnormalities, and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation. Currently, scholars have limited knowledge of this disease, and published cases are few. Further accumulation of diagnostic and treatment experiences is required. CASE SUMMARY: A 16-year-old girl experienced left upper limb swelling for 3 years. She sought medical attention at a local hospital 10 months ago, where magnetic resonance imaging revealed a 5-cm soft tissue mass. Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma. The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement. She was initially diagnosed with a synovial sarcoma. Consequently, clinical management with chemotherapy was continued for the malignant sarcoma. Our pathology department also performed fluorescence in situ hybridization for result validation, which returned negative for SS18 gene breaks, indicating that it was not a synovial sarcoma. Next-generation sequencing was used to identify the SRF-RELA rearrangement. The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion. The patient had initially received two courses of chemotherapy; however, chemotherapy was discontinued after the final diagnosis. CONCLUSION: This case was misdiagnosed because of its rare occurrence, benign biological behavior, and pathological similarity to soft tissue sarcoma.

Performance of VI-RADS in predicting muscle-invasive bladder cancer after transurethral resection: a single center retrospective analysis.

PURPOSE: To assess VIRADS performance and inter-reader agreement for detecting muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumor (TURBT). METHODS: An IRB-approved, HIPAA-compliant, retrospective study from 2016 to 2020 included patients with bladder urothelial carcinoma who underwent MRI after TURBT, and cystectomy within 3 months without post-MRI treatments. Three radiologists blinded to pathology results independently reviewed MR images and assigned a VI-RADS score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI-RADS were assessed for diagnosing MIBC using VI-RADS scores ≥ 3 and ≥ 4. Inter-reader agreement was assessed using Gwet's agreement coefficient (AC) and percent agreement. RESULTS: The cohort consisted of 70 patients (mean age, 68 years ± 11 [SD]; range 39-85; 58 men) and included 32/70 (46%) with MIBC at cystectomy. ROC analysis revealed an AUC ranging from 0.67 to 0.77 and no pairwise statistical difference between readers (p-values, 0.06, 0.08, 0.97). Percent sensitivity, specificity, PPV, NPV and accuracy for diagnosing MIBC for the three readers ranged from 81.3-93.8, 36.8-55.3, 55.6-60.5, 77.3-87.5, and 62.9-67.1 respectively for VI-RADS score ≥ 3, and 78.1-81.3, 47.4-68.4, 55.6-67.6, 72.0-78.8 and 61.4-72.9 respectively for VI-RADS score ≥ 4. Gwet's AC was 0.63 [95% confidence interval (CI): 0.49,0.78] for VI-RADS score ≥ 3 with 79% agreement [95% CI 72,87] and 0.54 [95%CI 0.38,0.70] for VI-RADS score ≥ 4 with 76% agreement [95% CI 69,84]. VIRADS performance was not statistically different among 31/70 (44%) patients who received treatments prior to MRI (p ≥ 0.16). CONCLUSION: VI-RADS had moderate sensitivity and accuracy but low specificity for detection of MIBC following TURBT, with moderate inter-reader agreement.

MRI, clinical, and radiomic models for differentiation of uterine leiomyosarcoma and leiomyoma.

PURPOSE: To assess the predictive ability of conventional MRI features and MRI texture features in differentiating uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS). METHODS: This single-center, IRB-approved, HIPAA-compliant retrospective study included 108 patients (69 LM, 39 LMS) who had pathology, preoperative MRI, and clinical data available at our tertiary academic institution. Two radiologists independently evaluated 14 features on preoperative MRI. Texture features based on 3D segmentation were extracted from T2W-weighted MRI (T2WI) using commercially available texture software (TexRAD™, Feedback Medical Ltd., Great Britain). MRI conventional features, and clinical and MRI texture features were compared between LM and LMS groups. Dataset was randomly divided into training (86 cases) and testing (22 cases) cohorts (8:2 ratio); training cohort was further subdivided into training and validation sets using ten-fold cross-validation. Optimal radiomics model was selected out of 90 different machine learning pipelines and five models containing different combinations of MRI, clinical, and radiomics variables. RESULTS: 12/14 MRI conventional features and 2/2 clinical features were significantly different between LM and LMS groups. MRI conventional features had moderate to excellent inter-reader agreement for all but two features. Models combining MRI conventional and clinical features (AUC 0.956) and MRI conventional, clinical, and radiomics features (AUC 0.989) had better performance compared to models containing MRI conventional features alone (AUC 0.846 and 0.890) or radiomics features alone (0.929). CONCLUSION: While multiple MRI and clinical features differed between LM and LMS groups, the model combining MRI, clinical, and radiomic features had the best predictive ability but was only marginally better than a model utilizing conventional MRI and clinical data alone.

The therapeutic effect of anti-CD19 antibody on DHEA-induced PCOS mice.

Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19+ B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21+ CD23low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.

Redesigned Nylon 6 Variants with Enhanced Recyclability, Ductility, and Transparency.

Geminal (gem-) disubstitution in heterocyclic monomers is an effective strategy to enhance polymer chemical recyclability by lowering their ceiling temperatures. However, the effects of specific substitution patterns on the monomer's reactivity and the resulting polymer's properties are largely unexplored. Here we show that, by systematically installing gem-dimethyl groups onto ϵ-caprolactam (monomer of nylon 6) from the α to ϵ positions, both the redesigned lactam monomer's reactivity and the resulting gem-nylon 6's properties are highly sensitive to the substitution position, with the monomers ranging from non-polymerizable to polymerizable and the gem-nylon properties ranging from inferior to far superior to the parent nylon 6. Remarkably, the nylon 6 with the gem-dimethyls substituted at the γ position is amorphous and optically transparent, with a higher Tg (by 30 °C), yield stress (by 1.5 MPa), ductility (by 3×), and lower depolymerization temperature (by 60 °C) than conventional nylon 6.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer.

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011-2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Fault-Tolerant Synchronization for Memristive Neural Networks With Multiple Actuator Failures.

By using the fault-tolerant control method, the synchronization of memristive neural networks (MNNs) subjected to multiple actuator failures is investigated in this article. The considered actuator failures include the effectiveness failure and the lock-in-place failure, which are different from previous results. First of all, the mathematical expression of the control inputs in the considered system is given by introducing the models of the above two types of actuator failures. Following, two classes of synchronization strategies, which are state feedback control strategies and event-triggered control strategies, are proposed by using some inequality techniques and Lyapunov stability theories. The designed controllers can, respectively, guarantee the realization of synchronizations of the global exponential, the finite-time and the fixed-time for the MNNs by selecting different parameter conditions. Then the estimations of settling times of provided synchronization schemes are computed and the Zeno phenomenon of proposed event-triggered strategies is explicitly excluded. Finally, two experiments are conducted to confirm the availability of given synchronization strategies.

Associations between gut microbiota and three prostate diseases: a bidirectional two-sample Mendelian randomization study.

According to previous observational researches and clinical trials, the gut microbiota is related to prostate diseases. However, the potential association between gut microbiota and prostate disorders is still uncertain. We first identified groups of gut microbiota based on the phylum, class, order, family, and genus levels from consortium MiBioGen. And we acquired prostate diseases statistics from the FINNGEN study and PRACTICAL consortium. Next, two-sample Mendelian randomization was used to investigate the potential associations between three prevalent prostate disease and gut microbiota. In addition, we performed a reverse MR analysis and Benjamini-Hochberg (BH) test for further research. We investigated the connection between 196 gut microbiota and three prevalent prostate diseases. We identified 42 nominally significant associations and 2 robust causative links. Upon correction for multiple comparisons using the Benjamini-Hochberg procedure, our analysis revealed a positive correlation between the risk of prostatitis and the presence of the taxonomic order Gastranaerophilales. Conversely, the risk of prostate cancer exhibited an inverse correlation with the presence of the taxonomic class Alphaproteobacteria. Our study revealed the potential association between gut microbiota and prostate diseases. The results may be useful in providing new insights for further mechanistic and clinical studies of prostate diseases.