HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis.

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Scalable parallel ultrafast optical random bit generation based on a single chaotic microcomb.

Random bit generators are critical for information security, cryptography, stochastic modeling, and simulations. Speed and scalability are key challenges faced by current physical random bit generation. Herein, we propose a massively parallel scheme for ultrafast random bit generation towards rates of order 100 terabit per second based on a single micro-ring resonator. A modulation-instability-driven chaotic comb in a micro-ring resonator enables the simultaneous generation of hundreds of independent and unbiased random bit streams. A proof-of-concept experiment demonstrates that using our method, random bit streams beyond 2 terabit per second can be successfully generated with only 7 comb lines. This bit rate can be easily enhanced by further increasing the number of comb lines used. Our approach provides a chip-scale solution to random bit generation for secure communication and high-performance computation, and offers superhigh speed and large scalability.

Assessing territorial space conflicts in the coastal zone of Wenzhou, China: A land-sea interaction perspective.

Territorial space conflicts (TSCs) in coastal zones stem from the intricate interaction between the land-sea dual system, significantly impacting the sustainable development of these areas. To accurately identify TSCs, our study proposed a theoretical framework based on a land-sea interaction perspective. We also assessed TSCs using the territorial space conflicts index and a social network analysis model. We demonstrated the proposed spatial conflicts assessment methodology through a case study of Wenzhou, a typical city on the east coast of China. Our results indicate that the distribution of TSCs gradually decreased from the coastal zone to the inland zone, with significant variation in the distribution of different conflict types across different zones. The findings also reveal that territorial space use had diverse impacts on the space conflict network, making it urgent to take targeted measures. In the future, it is crucial to comprehensively consider the overall pattern and distribution characteristics of current TSCs, as well as the spatial spillover effect of the overall network, to develop targeted coping strategies and regulation mechanisms that promote the integration and high-quality development of coastal territorial space systems. To maintain a sustainable coastal zone process, we proposed a set of optimization paths for alleviating TSCs and promoting the coordinated development of land and sea regions in China based on our study.

A multi-criteria simulation-optimization coupling approach for effective emergency response in marine oil spill accidents.

Effective marine oil spill responses are vital to reduce environmental, societal, and economic damage. This study developed a Multi-Criteria Emergency Response System (MC-ERS) to comprehensively evaluate response efficiency, operational costs, and environmental losses. The proposed system integrates dynamic multiphase simulation of oil weathering and oil cleanup processes and further provides effective planning for multi-stage resource allocation through system optimization. The developed weight-sum model improved the performance of response operations by reducing the complexity of multi-criteria decision-making. Particle Swarm Optimization (PSO) was chosen as the foundational optimization algorithm due to its efficiency in rapid convergence and suitability for complex problems. From extensive comparisons of PSO variants across benchmark functions and inertia strategies, the C-PSO algorithm was developed, demonstrating enhanced optimization performance for MC-ERS. The developed modelling system performance was demonstrated and evaluated through a representative case study. The optimization plan coordinated resource allocation from onshore warehouses to harbors and spill sites, balancing oil recovery efficiency, costs, and ecological losses. Optimized results indicate an oil recovery of up to 76.50% in five days. Additionally, the system cuts costs by 3.45% and environmental losses by 15.75%. The findings enhance the efficiency of marine oil spill emergency response and provide support for such incidents.

Effect of free radicals on rheological properties, antioxidant activity, and molecular conformation of chitosan under solution pulsed plasma process based on radical scavengers.

Radical scavengers were employed to evaluate the influence of various active species (•OH, •O, and H2O2) on the rheological properties, antioxidant activity, and molecular conformation of chitosan under solution plasma process (SPP) degradation. ESR analysis showed that •OH and •O radicals played important roles in SPP degradation. The results of rheological properties and antioxidant activity indicated that the •OH scavenger (tert-butanol), •O scavenger (1, 4-benzoquinone), and H2O2 scavenger (MnO2) remarkably inhibited the decrease of G' and G" of the degraded chitosan, the formation of gel structure, and the increase of antioxidant activity. The analysis of molecular conformation of the chitosan by particle size analysis, atomic force microscopy (AFM), and high performance size exclusion chromatography coupled with multi-angle laser light scattering (HPSEC-MALLS) revealed that the decrease of particle size, molecular aggregation, and molecular weight of chitosan was inhibited after the addition of radical scavengers. An evident effect of radical scavengers on the hard sphere conformation of chitosan was observed. It was found that the above effects were strongly dependent on the scavenger concentration. These results proved that •OH, •O, and H2O2 played important roles in SPP treatment. For the rheological properties and molecular conformation, H2O2 exhibited the greatest impact. For the antioxidant activity and molecular weight, •OH presented the biggest influence. Besides, •O expressed the weakest effect. This study will be beneficial to reveal the action mechanisms of SPP technology to the degradation of chitosan.

Retrospective analysis of the clinical significance of Ro52/TRIM21 antibody and specific antinuclear antibody patterns by indirect immunofluorescence.

Objectives: To determine the clinical significance of Ro52 protein/tripartite motif-containing 21 antibody and specific antinuclear antibody patterns using indirect immunofluorescence technique. METHODS: The retrospective study was conducted at the clinical laboratory of the First Affiliated Hospital of Chongqing Medical University, China, and comprised data from January 2017 to December 2021 of patients who underwent antinuclear antibody and anti-extractable nuclear antigen antibody detection. Inpatients with Ro52 antibody-positive status were taken as the cases, while anti-Ro52 negative patients with clear clinical diagnosis were taken as the controls. Data was analysed using SPSS 19. RESULTS: There were 1802 cases and 1211 controls. Positive Ro52 showed significantly greater frequency in patients with primary Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eyes and interstitial lung disease (p<0.05). Ro52 antibody showed high positive predictive value for primary Sjogren's syndrome 25(96.15%), systemic lupus erythematosus 259(91.20%), connective tissue disease-associated interstitial lung disease 45(86.67%) and inflammatory myositis 60(86.67%). Antinuclear antibody indirect immunofluorescence patterns most frequently detected were nuclear speckled 128(40.89%) and cytoplasmic speckled 126(40.26%) (p<0.05). Interstitial lung disease was associated with the presence of cytoplasmic speckled antinuclear antibody indirect immunofluorescence pattern 24(19.2%), while tumours 47(36.5%) and hepatitis B 26(20.3%) seemed to be more frequent with nuclear speckled pattern (p<0.05). The simultaneous reactivity extractable nuclear antigen antibodies most frequently detected were antinuclear antibody+Ro52+anti-Sjogren's syndrome A+ 558(33.96%). CONCLUSIONS: Ro52 antibody positivity was found to be associated with Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eye and interstitial lung disease. The antinuclear antibody immunofluorescence pattern of Ro52 positive was single and primarily granular cytoplasm type. Antinuclear antibody negative and Ro52 positive in the serum of patients also had certain significance in auxiliary disease diagnosis.

The role of type VI secretion system genes in antibiotic resistance and virulence in Acinetobacter baumannii clinical isolates.

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed. Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated. Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella. Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

ER-positive and BRCA2-mutated breast cancer: a literature review.

BRCA2-mutated carriers have a high lifetime risk of breast cancer (BC), an early age of onset, and an increased risk of other cancers (including ovarian, pancreatic, and prostate cancer). Almost 70-80% of BRCA2-mutated BC are estrogen receptor (ER)-positive, which is a particular type of ER-positive BC that differs from sporadic ER-positive BC. This article reviews the clinicopathological features, treatment, and prognosis of ER-positive and BRCA2-mutated BC to provide a reference for clinical decision-making.

Direct chemical-vapor-deposition growth of alloyed perovskite microcrystals for tunable emissions.

Tunable composition of perovskite micro/nanostructures are perfect candidate for the designing of multifunctional optoelectronic circuits. Especially, integrated polychromatic luminescence based on the perovskite materials along a single substrate or chip is essential to the integrated photonic devices and multicolor displays. Here, we reported a synthesis of composition tunable CsPbI3(1-x)Br3x(X = 0.65-0.9) perovskite microstructures on a single substrate via a magnetic-pulling CVD method. The PL emissions can be changed gradually from green (558 nm, 2.23 eV) to red (610 nm, 2.03 eV) under a focused 375 nm laser illumination. Furthermore, these composition-graded alloyed perovskite microcrystals show stable emissions after six months in air, which may find applications in multicolor display and broad band light sources in the future.

Clinical Observation of Various Types of Idiopathic Hypertrophic Cranial Pachymeningitis.

BACKGROUND: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP). METHODS: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up. RESULTS: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types. CONCLUSIONS: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients.

Aging of plastics in aquatic environments: Pathways, environmental behavior, ecological impacts, analyses and quantifications.

The ubiquity of plastics in our environment has brought about pressing concerns, with their aging processes, photo-oxidation, mechanical abrasion, and biodegradation, being at the forefront. Microplastics (MPs), whether originating from plastic degradation or direct anthropogenic sources, further complicate this landscape. This review delves into the intricate aging dynamics of plastics in aquatic environments under various influential factors. We discuss the physicochemical changes that occur in aged plastics and the release of oxidation products during their degradation. Particular attention is given to their evolving environmental interactions and the resulting ecotoxicological implications. A rigorous evaluation is also conducted for methodologies in the analysis and quantification of plastics aging, identifying their merits and limitations and suggesting potential avenues for future research. This comprehensive review is able to illuminate the complexities of plastics aging, charting a path for future research and aiding in the formulation of informed policy decisions.

Air particulate pollution exposure associated with impaired cognition via microbiota gut-brain axis: an evidence from rural elderly female in northwest China.

This study aimed to reveal harm of exposure to indoor air pollution to cognitive function through "gut-brain-axis" among rural elderly residents. There were 120 participants recruited in rural villages of northwest China from December 2021 to February 2022. The cognitive level was assessed by eight-item ascertain dementia (AD) questionnaire, and indoor air pollution exposure was measured by air quality sensor. Inflammatory cytokines and oxidative stress-related index were detected in blood serum. Fecal samples were collected for gut microbiota analysis. The 120 participants were divided into impaired cognition (AD8) (81/67.5%) and cognition normal (NG) (39/32.5%). And there had more female in AD8 (FAD) (55/67.9%) than NG (FNG) (18/46.2%) (P = 0.003). Exposure of air pollution in FAD was higher than FNG (PM1, PM2.5, PM10, P < 0.001; NO2, P < 0.001; CO, P = 0.014; O3, P = 0.002). The risk of cognitive impairment increases 6.8%, 3.6%, 2.6%, 11%, and 2.4% in female for every 1 µg/m3 increased in exposure of PM1, PM2.5, PM10, NO2, and O3, separately. And GSH-Px and T-SOD in FAD were significantly lower than the FNG group (P = 0.011, P = 0.019). Gut microbiota in FAD is disordered with lower richness and diversity. Relative abundance of core bacteria Faecalibacterium (top 1 genus) in FAD was reduced (13.65% vs 19.81%, P = 0.0235), while Escherichia_Shigella and Akkermansia was increased. Correlation analysis showed Faecalibacterium was negatively correlated with age, and exposure of O3, PM1, PM2.5, and PM10; Akkermansia and Monoglobus were positively correlated with exposure of PM1, PM2.5 and PM10; Escherichia_Shigella was significantly positively correlated with NO2. Indoor air pollution exposure impaired cognitive function in elderly people, especially female, which may cause systemic inflammation, dysbiosis of the gut microbiota, and ultimately leading to early cognitive impairment through the gut-brain axis.

A Photoelectrochemical Sensor Based on DNA Bio-Dots-Induced Aggregation of AuNPs for Methionine Detection.

Based on DNA bio-dots-induced aggregation of gold nanoparticles (AuNPs), a methionine (Met) photoelectrochemical (PEC) sensor with CS-GSH-CuNCs/TiO2 NPs as the photoelectric conversion element and AuNPs as the specific recognition element was constructed. First, a TiO2 NPs/ITO electrode and CS-GSH-CuNCs were prepared, and then the CS-GSH-CuNCs/TiO2 NPs/ITO photosensitive electrode was obtained by self-assembly. Next, DNA bio-dots were modified to the upper surface of the electrode using a coupling reaction to assemble the DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Amino-rich DNA bio-dots were used to induce the aggregation of AuNPs on the electrode surface via Au-N interactions and prepare the AuNPs/DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Due to the fluorescence resonance energy transfer (FRET) between CS-GSH-CuNCs and AuNPs, the complexation chance of electron-hole (e--h+) pair in CS-GSH-CuNCs increased, which, in turn, led to a decrease in photocurrent intensity. When Met was present, AuNPs aggregated on the electrode surface were shed and bound to Met since the Au-S interaction is stronger than the Au-N interaction, resulting in the recovery of the photocurrent signal. Under optimal conditions, the photocurrent intensity of the PEC sensor showed good linearity with the logarithm of Met concentration in the range of 25.0 nmol/L-10.0 µmol/L with the limit of detection (LOD) of 5.1 nmol/L (S/N = 3, n = 10).

Integrative analysis of transcriptomic and metabolomic profiles reveals enhanced arginine metabolism in androgen-independent prostate cancer cells.

BACKGROUND: Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of developing castration-resistant prostate cancer (CRPC). Effective clinical management of patients with CRPC is challenging due to the limited understanding. METHODS: In this study, transcriptomic and metabolomic profiles of androgen-dependent prostate cancer cell line LNCaP and the androgen-independent cells developed from LNCaP cells (LNCaP-ADR) were investigated using RNA-sequencing and LC-MS/MS, respectively. The differentially expressed genes and metabolites were analyzed, and integrative analysis of transcriptomic and metabolomic data was further conducted to obtain a comprehensive understanding of the metabolic characteristics in LNCaP-ADR cells. Quantitative real-time PCR (QPCR) was employed to ascertain the mRNA expression levels of the selected differentially expressed genes. RESULTS: The arginine and proline metabolism pathway was identified as a commonly altered pathway at both the transcriptional and metabolic levels. In the LNCaP-ADR cells, significant upregulation was observed for metabolites including 5-Aminopentanoic acid, L-Arginine, L-Glutamic acid, N-Acetyl-L-alanine, and Pyrrole-2-carboxylic acid at the metabolic level. At the transcriptional level, MAOA, ALDH3A2, ALDH2, ARG1, CKMT2, and CNDP1 were found to be significantly upregulated in the LNCaP-ADR cells. Gene set enrichment analysis (GSEA) identified various enriched gene sets in the LNCaP-ADR cells, encompassing inflammatory response, 9plus2 motile cilium, motile cilium, ciliary plasm, cilium or flagellum-dependent cell motility, cilium movement, cilium, response to endoplasmic reticulum stress, PTEN DN.V1 DN, SRC UP.V1 UP, IL15 UP.V1 DN, RB DN.V1 DN, AKT UP MTOR DN.V1 UP, VEGF A UP.V1 UP, and KRAS.LUNG.BREAST UP.V1 UP. CONCLUSIONS: These findings highlight the substantial association between the arginine and proline metabolism pathway and CRPC, emphasizing the need to prioritize strategies that target dysregulated metabolites and differentially expressed genes as essential interventions in the clinical management of CRPC.

Transcriptomic and phenotype analysis revealed the role of rpoS in stress resistance and virulence of a novel ST3355 ESBL-producing hypervirulent Klebsiella pneumoniae isolate.

Introduction: An extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient. Methods: The effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated. Results: HKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing. Discussion: Here, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.

Combined deep-learning MRI-based radiomic models for preoperative risk classification of endometrial endometrioid adenocarcinoma.

Background: Differences exist between high- and low-risk endometrial cancer (EC) in terms of whether lymph node dissection is performed. Factors such as tumor grade, myometrial invasion (MDI), and lymphovascular space invasion (LVSI) in the European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guidelines risk classification can often only be accurately assessed postoperatively. The aim of our study was to estimate the risk classification of patients with endometrial endometrioid adenocarcinoma before surgery and offer individualized treatment plans based on their risk classification. Methods: Clinical information and last preoperative pelvic magnetic resonance imaging (MRI) of patients with postoperative pathologically determined endometrial endometrioid adenocarcinoma were collected retrospectively. The region of interest (ROI) was subsequently plotted in T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) MRI scans, and the traditional radiomics features and deep-learning image features were extracted. A final radiomics nomogram model integrating traditional radiomics features, deep learning image features, and clinical information was constructed to distinguish between low- and high-risk patients (based on the 2020 ESMO-ESGO-ESTRO guidelines). The efficacy of the model was evaluated in the training and validation sets of the model. Results: We finally included 168 patients from January 1, 2020 to July 29, 2021, of which 95 patients in 2021 were classified as the training set and 73 patients in 2020 were classified as the validation set. In the training set, the area under the curve (AUC) of the radiomics nomogram was 0.923 (95%CI: 0.865-0.980) and in the validation set, the AUC of the radiomics nomogram was 0.842 (95%CI: 0.762-0.923). The nomogram had better predictions than both the traditional radiomics model and the deep-learning radiomics model. Conclusion: MRI-based radiomics models can be useful for preoperative risk classification of patients with endometrial endometrioid adenocarcinoma.

Marine oil spill photodegradation: Laboratory simulation, affecting factors analysis and kinetic model development.

Photodegradation significantly influences marine oil spill behavior, yet its role remains underrepresented in current models, impairing predictive accuracy. Addressing this, our study rigorously examined oil properties and environmental determinants affecting marine oil spill photodegradation through laboratory simulations. We identified and quantified key factors and their interactions, noting particularly the positive influence of asphaltene and negative implications of oil density. We also discerned a negative correlation between n-alkane degradation and carbon numbers. Our findings underscored the pivotal roles of temperature and irradiance in photodegradation. All tested oils adhered to first-order kinetics, with rate constants ranging from 0.0348 to 0.0645 day-1. Finally, we introduced a novel model incorporating temperature, irradiance and their interactions, ensuring reasonable simulations for marine oil spill photodegradation, fortifying marine oil spill management strategies.

Curcumin strengthens a spontaneous self-protective mechanism-SP1/PRDX6 pathway, against di-n-butyl phthalate-induced testicular ferroptosis damage.

As one of the common plasticizers, di-n-butyl phthalate (DBP) has been using in various daily consumer products worldwide. Since it is easily released from products and exists in the environment for a long time, it has a lasting impact on human health, especially male reproductive health. However, the detailed mechanism of testicular damage from DBP and the protection strategy are still not clear enough. In this study, we found that DBP could induce dose-dependent ferroptosis in testicular tissue. Mechanism dissection indicates that DBP can upregulate SP1 expression, which could directly transcriptionally upregulate PRDX6, a negative regulator of ferroptosis. Overexpression of PRDX6 or adding SP1 agonist curcumin could suppress the DBP-induced ferroptosis on testicular cells. In vivo, rats were given 500 mg/kg/day DBP orally for 3 weeks; elevated levels of ferroptosis were detected in testicular tissue. When the above-mentioned doses of DBP and curcumin at a dose of 300 mg/kg/day were administered intragastrically simultaneously, the testicular ferroptosis induced by DBP was alleviated. Immunohistochemistry and quantitative real-time PCR of testis tissue showed that the expression of PRDX6 was upregulated under the action of DBP and curcumin. These findings suggest a spontaneous self-protection mechanism of testicular tissue from DBP damage by upregulating SP1 and PRDX6. However, it is not strong enough to resist the DBP-induced ferroptosis. Curcumin can strengthen this self-protection mechanism and weaken the level of ferroptosis induced by DBP. This study may help us to develop a novel therapeutic option with curcumin to protect the testicular tissue from ferroptosis and function impairment by DBP.

Gasdermin D: A Potential New Auxiliary Pan-Biomarker for the Detection and Diagnosis of Diseases.

Pyroptosis is a form of programmed cell death mediated by gasdermins, particularly gasdermin D (GSDMD), which is widely expressed in tissues throughout the body. GSDMD belongs to the gasdermin family, which is expressed in a variety of cell types including epithelial cells and immune cells. It is involved in the regulation of anti-inflammatory responses, leading to its differential expression in a wide range of diseases. In this review, we provide an overview of the current understanding of the major activation mechanisms and effector pathways of GSDMD. Subsequently, we examine the importance and role of GSDMD in different diseases, highlighting its potential as a pan-biomarker. We specifically focus on the biological characteristics of GSDMD in several diseases and its promising role in diagnosis, early detection, and differential diagnosis. Furthermore, we discuss the application of GSDMD in predicting prognosis and monitoring treatment efficacy in cancer. This review proposes a new strategy to guide therapeutic decision-making and suggests potential directions for further research into GSDMD.

The Impact of ESBLs-Positive Escherichia coli's Resistance to Cefepime and Its Guidance for Clinical Treatment.

Background: Escherichia coli (E. coli) is a common pathogen in bloodstream infections (BSI), and the production of extended-spectrum beta-lactamases (ESBLs) is its main mechanism of resistance. However, the impact of different ESBL genotypes of E. coli on the resistance to Cefepime (FEP) remains unclear. Methods: A total of 2356 cases of BSI patients were collected. The experimental group included 188 ESBL-positive E. coli strains that were resistant to FEP but sensitive to ceftazidime (CAZ). Antibiotic usage and resistance rates were evaluated through antimicrobial susceptibility testing and antibiotic usage records. The ESBL genotypes were identified, and the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of FEP were determined. Results: In ESBL-positive E. coli, three ESBL genotypes were identified: 188 strains of CTX-M, 130 strains of TEM-1, and 26 strains of OXA-10. Among them, 124 strains carried both CTX-M-9 and TEM-1 genotypes, 22 strains carried two CTX-M genotypes (CTX-M-1 and CTX-M-2), 20 strains carried both CTX-M-9 and OXA-10, and 6 strains carried three genotypes (CTX-M-9, CTX-TEM-1, and OXA-10). The MIC50, MIC90, MPC50, and MPC90 of the 188 ESBL-positive E. coli were 64, 256, 128, and 528, respectively. The MIC values ranged from 32 to 256, while the MPC values ranged from 64 to 528. The MIC50, MIC90, MPC50, and MPC90 of the 40 ESBL-negative E. coli were 0.5, 1, 64, and 128, respectively; the MIC values ranged from 0.25 to 4, while the MPC values ranged from 32 to 256, respectively. Conclusion: ESBL-positive E. coli induces an increase in the MIC value of FEP, leading to an increase in FEP resistance. The inoculation effect also causes a significant increase in the MPC value of FEP, especially the increase in selection index value, indicating selective enrichment and amplification of drug-resistant mutants, resulting in clinical treatment failure.