Liquid biopsy for early cancer detection: technological revolutions and clinical dilemma.

INTRODUCTION: Liquid biopsy is an innovative advancement in oncology, offering a noninvasive method for early cancer detection and monitoring by analyzing circulating tumor cells, DNA, RNA, and other biomarkers in bodily fluids. This technique has the potential to revolutionize precision oncology by providing real-time analysis of tumor dynamics, enabling early detection, monitoring treatment responses, and tailoring personalized therapies based on the molecular profiles of individual patients. AREAS COVERED: In this review, the authors discuss current methodologies, technological challenges, and clinical applications of liquid biopsy. This includes advancements in detecting minimal residual disease, tracking tumor evolution, and combining liquid biopsy with other diagnostic modalities for precision oncology. Key areas explored are the sensitivity, specificity, and integration of multi-omics, AI, ML, and LLM technologies. EXPERT OPINION: Liquid biopsy holds great potential to revolutionize cancer care through early detection and personalized treatment strategies. However, its success depends on overcoming technological and clinical hurdles, such as ensuring high sensitivity and specificity, interpreting results amidst tumor heterogeneity, and making tests accessible and affordable. Continued innovation and collaboration are crucial to fully realize the potential of liquid biopsy in improving early cancer detection, treatment, and monitoring.

Toxic effects of avermectin on liver function, gut microbiota, and colon barrier in the rat model.

Avermectin (AVM), a compound derived from the fermentation of Avermectin Streptomyces, has insecticidal, acaricidal, and nematicidal properties. Widely employed in agriculture, it serves as an effective and broad-spectrum insecticide for pest control. Although the toxicity of AVM at low doses may not be readily apparent, prolonged and extensive exposure can result in poisoning. To investigate the toxic effects of AVM on the body, this study established rat models of AVM poisoning with both low and high concentrations of the compound. Fifteen male rats were randomly assigned to one of three groups (n=5 per group): a control group, a low-concentration group, and a high-concentration group. The low-concentration group was administered an oral dose of 2 mg/kg AVM once daily for a duration of seven days, while the high-concentration group received an oral dose of 10 mg/kg AVM once daily for the same period. This study examined the impact of AVM on liver function and gut microbiota in rats using weight monitoring, liver function indicator detection, liver metabolomics sequencing, colon barrier function testing, and gut microbiota sequencing. The findings of this study demonstrated that exposure to 2 or 10 mg/kg AVM for seven days can lead to a notable decrease in rat weight, as well as induce liver dysfunction and metabolic disturbances. Additionally, AVM exposure can disrupt the composition of the intestinal microbiota and impair the integrity of the colon mucosal barrier, causing downregulation of Occludin expression and upregulation of inflammation-related protein expression levels such as IL-1ß, Myd88, and TLR4. Furthermore, bioinformatics analysis revealed a significant association between liver dysfunction and dysbiosis of the gut microbiota. These findings have implications for the agricultural use of AVM and its potential contribution to environmental pollution. Consequently, individuals involved in AVM usage should prioritize safety precautions and monitor liver function.

Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-ß/SMAD Pathway.

PURPOSE: To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus-induced erectile dysfunction (DMED). MATERIALS AND METHODS: DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose (HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins. RESULTS: Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and that the TGF-ß pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-ß signaling, as well as the overexpression of collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs. CONCLUSIONS: TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile dysfunction by inhibiting the TGF-ß/SMAD pathway.

A study of the pharmacokinetics of clozapine and its metabolites by the dynamics of its distribution in the oral fluid of healthy volunteers.

Clozapine (CLZ) -related accidents or crimes are common in the world. Oral fluid drug detection is a convenient measure of dealing with things like that. There has not been any literature reported detailedly the representation rule of clozapine and its metabolites in oral fluid so far. The study aimed to describe the pharmacokinetics of CLZ and its metabolites N-desmethylclozapine and clozapine-N-oxide in human oral fluid after a single 12.5 mg oral dose of CLZ. Twenty-nine volunteers, including 20 males and 9 females, were recruited, and 2 mL oral fluid was collected from each participant at post-consumption time-points of prior (zero), 0.5, 1.5, 3, 5, 8, 12, 24, 36, 51, 82, and 130 h, respectively. Analytes of interest were extracted with solid-phase extraction and analyzed with liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using the pharmacokinetic software DAS according to the non-compartment model. The maximum concentration, the time of maximum concentration, oral clearance, and the elimination half-life of clozapine were 16.57 ± 9.63 ng/mL, 4.53 ± 3.61 h, 57.65 ± 23.77 L/h and 53.58 ± 52.28 h, respectively. The maximum concentration, the time of maximum concentration, and the elimination half-life of the metabolite N-desmethylclozapine were 3.08 ± 1.19 ng/mL, 9.38 ± 9.33 h and 62.67 ± 82.57 h, respectively; of clozapine-N-oxide were 1.15 ± 0.36 ng/mL, 4.53 ± 2.19 h and 19.15 ± 23.11 h, respectively. It was the first study on the pharmacokinetics of CLZ and its metabolites in the oral fluid of Chinese healthy volunteers, and it provided a basis for the therapeutic drug monitoring and toxicological interpretation in clozapine-related cases.

Fucoidan from Laminaria japonica protects renal tubular epithelial cells from uric acid induced NLRP3-mediated pyroptosis through inhibition of NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperuricemia is a common metabolic disease with prominent morbidity, it can lead to many adverse effects and complications, such as chronic nephrosis. Fucoidan has been used as natural drug for acute and chronic kidney disease for over 20 years in China, but the precise mechanisms underlying the renal protective function are still indefinable. PURPOSE: This study is conducted to explore alleviation of fucoidan (FPS) from Laminaria japonica on urate-induced NOD-like receptor family, pyrin domain-containing 3 (NLRP3)-mediated pyroptosis in renal tubular epithelial cells HK-2, as well as the mechanism of nuclear factor κB (NF-κB) signaling pathway involved. MATERIALS AND METHODS: HK-2 cells were treated with FPS, uric acid (UA), and inhibitor of NF-κB signaling pathway. Nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity were determined with detection kits. Activation of intercellular NLRP3 inflammasome and NF-κB signaling pathway, gasdermin D (GSDMD) expression level were evaluated with Western blot and quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescent analysis. RESULTS: Data showed that UA induced cellular inflammatory response demonstrated by elevated NO content, iNOS activity and expression level of NLRP3 inflammasome-mediated pyroptosis associated molecules including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1, interleukin 18 (IL-18) and GSDMD, moreover the NF-κB signaling pathway was activated by UA. However, FPS exposure inhibited efficiently the UA induced adverse effect. CONCLUSION: It can be concluded that FPS inhibited UA-induced NLRP3-mediated pyroptosis in HK-2 cells through repressing NF-κB signaling pathway.

Multiclass motor imagery classification with Riemannian geometry and temporal-spectral selection.

Motor imagery (MI) based brain-computer interfaces (BCIs) decode the users' intentions from electroencephalography (EEG) to achieve information control and interaction between the brain and external devices. In this paper, firstly, we apply Riemannian geometry to the covariance matrix extracted by spatial filtering to obtain robust and distinct features. Then, a multiscale temporal-spectral segmentation scheme is developed to enrich the feature dimensionality. In order to determine the optimal feature configurations, we utilize a linear learning-based temporal window and spectral band (TWSB) selection method to evaluate the feature contributions, which efficiently reduces the redundant features and improves the decoding efficiency without excessive loss of accuracy. Finally, support vector machines are used to predict the classification labels based on the selected MI features. To evaluate the performance of our model, we test it on the publicly available BCI Competition IV dataset 2a and 2b. The results show that the method has an average accuracy of 79.1% and 83.1%, which outperforms other existing methods. Using TWSB feature selection instead of selecting all features improves the accuracy by up to about 6%. Moreover, the TWSB selection method can effectively reduce the computational burden. We believe that the framework reveals more interpretable feature information of motor imagery EEG signals, provides neural responses discriminative with high accuracy, and facilitates the performance of real-time MI-BCI.

The neuroprotective effects of caffeic acid phenethyl ester against methamphetamine-induced neurotoxicity.

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

Mechanism of salt tolerance in the endangered semi-mangrove plant Barringtonia racemosa: anatomical structure and photosynthetic and fluorescence characteristics.

To elucidate the mechanisms governing the salt tolerance of the endangered semi-mangrove plant Barringtonia racemosa, the biomass, photosynthetic and fluorescent characteristics, and anatomical structure of B. racemosa were studied under low, medium and high salt stress. The results showed that the stem dry weight, net photosynthetic rate, intercellular CO2 concentration, Fv/Fm, and ΦPSI of B. racemosa decreased under high salt stress, which led to a significant reduction in total dry weight. Stem dry weight was significantly positively correlated with the thickness of palisade tissue and significantly negatively correlated with the thickness of the epidermis of roots and xylem of stems. Therefore, a stable net photosynthetic rate and intercellular CO2 concentration, an increase in Fv/Fm and ΦPSI, an increase in or stable palisade tissue and spongy mesophyll of leaves and an increase in xylem thickness of the stem and epidermis, outer cortex, and stele diameter of roots could contribute to the salt tolerance of B. racemosa.

Sudden death with cardiac involvement in a neonate with carnitine-acylcarnitine translocase deficiency.

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases.

Modified Ileal Conduit for Pelvic Lipomatosis: Technique Description and Outcome.

INTRODUCTION: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

Administration of blue light in the morning and no blue-ray light in the evening improves the circadian functions of non-24-hour shift workers.

In modern 24-hour society, various round-the-clock services have entailed shift work, resulting in non-24-hour schedules. However, the extent of behavioral and physiological alterations by non-24-hour schedules remains unclear, and particularly, effective interventions to restore the circadian functions of non-24-hour shift workers are rarely explored. In this study, we investigate the effects of a simulated non-24-hour military shift work schedule on daily rhythms and sleep, and establish an intervention measure to restore the circadian functions of non-24-hour shift workers. The three stages of experiments were conducted. The stage-one experiment was to establish a comprehensive evaluation index of the circadian rhythms and sleep for all 60 participants by analyzing wristwatch-recorded physiological parameters and sleep. The stage-two experiment evaluated the effects of an intervention strategy on physiological rhythms and sleep. The stage-three experiment was to examine the participants' physiological and behavioral disturbances under the simulated non-24-hour military shift work schedule and their improvements by the optimal lighting apparatus. We found that wristwatch-recorded physiological parameters display robust rhythmicity, and the phases of systolic blood pressures and heart rates can be used as reliable estimators for the human body time. The simulated non-24-hour military shift work schedule significantly disrupts the daily rhythms of oxygen saturation levels, blood pressures, heart rates, and reduces sleep quality. Administration of blue light in the morning and no blue-ray light in the evening improves the amplitude and synchronization of daily rhythms of the non-24-hour participants. These findings demonstrate the harmful consequences of the non-24-hour shift work schedule and provide a non-invasive strategy to improve the well-being and work efficiency of the non-24-hour shift population.

Moral courage and its influencing factor among oncology specialist nurses: A multi-centre cross-sectional study.

AIM: Moral courage among healthcare workers has been extensively studied. However, few studies have been conducted on oncology specialist nurses, who frequently encounter complex moral situations. This study aimed to describe the current situation regarding moral courage and explored its influence on oncology specialist nurses in China. DESIGN: This was an exploratory, descriptive study. METHODS: A convenience sample of 390 nurses was conducted from 15 hospitals in Sichuan Province, China, between March and May 2023. Participants were assessed using the Moral Distress Scale-Revised, Nurses' Moral Courage Scale and the Moral Sensitivity Questionnaire. RESULTS: The results demonstrated that moral courage was negatively associated with moral distress, and positively associated with moral sensitivity. Having a master's degree or above, an intermediate title or senior title, medical ethics training, moral distress or moral sensitivity contributed to explaining 54.1% of the variance in moral courage. CONCLUSIONS: Moral courage was associated with several factors. Developing clinical intervention strategies and effective teaching methods will be critical for improving moral courage. No Patient or Public Contribution.

Aquilaria sinensis leaf tea affects the immune system and increases sleep in zebrafish.

The importance of adequate sleep for good health cannot be overstated. Excessive light exposure at night disrupts sleep, therefore, it is important to find more healthy drinks that can promote sleep under sleep-disturbed conditions. The present study investigated the use of A. sinensis (Lour.) Spreng leaf tea, a natural product, to reduce the adverse effects of nighttime light on sleep. Here, Aquilaria sinensis leaf tea at 1.0 and 1.5 g/L significantly increased sleep time in zebrafish larvae (5-7 dpf) with light-induced sleep disturbance. Transcriptome sequencing and qRT-PCR analysis revealed a decrease in the immune-related genes, such as nfkbiab, tnfrsf1a, nfkbiaa, il1b, traf3, and cd40 in the 1.5 g/L Aquilaria sinensis leaf tea treatment group. In addition, a gene associated with sleep, bhlhe41, showed a significant decrease. Moreover, Aquilaria sinensis leaf tea suppressed the increase in neutrophils of Tg(mpo:GFP) zebrafish under sleep-disturbed conditions, indicating its ability to improve the immune response. Widely targeted metabolic profiling of the Aquilaria sinensis tea using ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) revealed flavonoids as the predominant component. Network pharmacological and molecular docking analyses suggested that the flavonoids quercetin and eupatilin in Aquilaria sinensis leaf tea improved the sleep of zebrafish by interacting with il1b and cd40 genes under light exposure at night. Therefore, the results of the study provide evidence supporting the notion that Aquilaria sinensis leaf tea has a positive impact on sleep patterns in zebrafish subjected to disrupted sleep due to nighttime light exposure. This suggests that the utilization of Aquilaria sinensis leaf tea as a potential therapeutic intervention for sleep disturbances induced by light may yield advantageous outcomes.

Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation.

Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of the G-protein-coupled receptor (APJ), is abundantly expressed in diverse organs. The apelin-APJ axis helps to control pathological and physiological processes in lung. The role of apelin in the pathological process and its possible therapeutic effects on silicosis have not been elucidated. In this study, we found that lung expression and circulating levels of apelin were markedly decreased in silicosis patients and silica-induced fibrotic mice and associated with the severity. Furthermore, in vivo data demonstrated that pre-treatment from day 3 and post-treatment from day 15 with apelin could both alleviate silica-induced pulmonary fibrosis in mice. Besides, apelin inhibited pulmonary fibroblast activation via transforming growth factor beta 1 (TGF-ß1) signaling. Our study suggested that apelin could prevent and reverse silica-induced pulmonary fibrosis by inhibiting the fibroblast activation through TGF-ß1 signaling pathway, thus providing a new potential therapeutic strategy for silicosis and other pulmonary fibrosis.

Air sparging remediation of VOCs contaminated low-permeability soil based on pressure gradient control.

Air sparging (AS) is deemed unacceptable for remediating VOCs contaminated soil with low-permeability. To improve air flow and contaminant removal in sparging process, an original approach, termed as pressure gradient-enhanced air sparging (PGEAS) approach, is proposed by controlling pressure gradient in soil. Then the remediation efficiency, mass transfer characteristics, and remediation mechanism are investigated. Results showed that, the PGEAS approach accelerates gaseous contaminant exhaust, reduces residue contamination in soil, and promotes total contaminant removal, finally results in an improved remediation efficiency compared to the conventional approach. Controlled by sparging pressure and flow distance, the pressure gradient is created in soil, and a critical value needs to be exceeded to enhance the VOCs removal and mass transfer characteristics. The measured results of pore pressure and liquid saturation confirm a notable pressure gradient and drainage behavior in soil, which indicate the massive air subchannel formation during air sparging. At a two-dimensional scale, discrete distributions of contaminant concentrations in exhaust air and soil are presented, the removal extent and area are both enhanced using the PGEAS approach with a pressure gradient higher than the critical value. The reached conclusions are of great importance to contaminant removal in heterogeneous stratigraphy at sites.

Review of the Interactions between Conventional Cementitious Materials and Heavy Metal Ions in Stabilization/Solidification Processing.

In the past few decades, solidification/stabilization (S/S) technology has been put forward for the purpose of improving soil strength and inhibiting contaminant migration in the remediation of heavy metal-contaminated sites. Cement, lime, and fly ash are among the most common and effective binders to treat contaminated soils. During S/S processing, the main interactions that are responsible for improving the soil's behaviors can be summarized as gelification, self-hardening, and aggregation. Currently, precipitation, incorporation, and substitution have been commonly accepted as the predominant immobilization mechanisms for heavy metal ions and have been directly verified by some micro-testing techniques. While replacement of Ca2+/Si4+ in the cementitious products and physical encapsulation remain controversial, which is proposed dependent on the indirect results. Lead and zinc can retard both the initial and final setting times of cement hydration, while chromium can accelerate the initial cement hydration. Though cadmium can shorten the initial setting time, further cement hydration will be inhibited. While for mercury, the interference impact is closely associated with its adapted anion. It should be pointed out that obtaining a better understanding of the remediation mechanism involved in S/S processing will contribute to facilitating technical improvement, further extension, and application.

Transcriptome analysis highlights the role of ferroptosis in palmitic acid-induced endothelial dysfunction.

Background: Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood. Aim: We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis. Methods: Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe2+), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins. Outcomes: At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe2+, and ROS. Results: PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe2+, MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death. Clinical Translation: This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction. Strengths and Limitations: In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed. Conclusion: Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion.

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.

Rare, fatal pulmonary fat embolism after acupuncture therapy: A case report and literature review.

BACKGROUND: Death from nontraumatic pulmonary fat embolism associated with minor soft tissue contusion, surgery, cancer chemotherapy, hematologic disorders and so on has been reported. Patients often present with atypical manifestations and rapid deterioration, making diagnosis and treatment difficult. However, there are no reported cases of death from pulmonary fat embolism after acupuncture therapy. This case emphasizes that the stress induced by acupuncture therapy, a mild soft tissue injury, plays an important role in pulmonary fat embolism. In addition, it suggests that in such cases, pulmonary fat embolism as a complication of acupuncture therapy needs to be taken seriously, and autopsy should be used to identify the source of fat emboli. CASE PRESENTATION: The patient was 72 years old female and experienced dizziness and fatigue after silver-needle acupuncture therapy. She experienced a significant drop in blood pressure and died 2 h later despite treatment and resuscitation. A systemic autopsy and histopathology examination (H&E and Sudan Ⅲ staining) were performed. More than 30 pinholes were observed in the lower back skin. Focal hemorrhages were seen surrounding the pinholes in the subcutaneous fatty tissue. Microscopically, numerous fat emboli were observed in the interstitial pulmonary arteries and alveolar wall capillaries, in addition to the vessels of the heart, liver, spleen and thyroid gland. The lungs showed congestion and edema. The cause of death was identified as pulmonary fat embolism. CONCLUSION: This article suggests that high vigilance for risk factors and the complication of pulmonary fat embolism following silver-needle acupuncture therapy should be exercised. In postmortem examinations, it should be pay attention that the peripheral arterial system and the venous system draining from non-injured sites should be examined for the formation of fat emboli, which can help distinguish posttraumatic and nontraumatic pulmonary fat embolism.