From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death.

Regulated cell death (RCD), also known as programmed cell death (PCD), plays a critical role in various biological processes, such as tissue injury/repair, development, and homeostasis. Dysregulation of RCD pathways can lead to the development of many human diseases, such as cancer, neurodegenerative disorders, and cardiovascular diseases. Maintaining proper metal ion homeostasis is critical for human health. However, imbalances in metal levels within cells can result in cytotoxicity and cell death, leading to a variety of diseases and health problems. In recent years, new types of metal overload-induced cell death have been identified, including ferroptosis, cuproptosis, and calcicoptosis. This has prompted us to examine the three defined metal-dependent cell death types, and discuss other metals-induced ferroptosis, cuproptosis, and disrupted Ca2+ homeostasis, as well as the roles of Zn2+ in metals' homeostasis and related RCD. We have reviewed the connection between metals-induced RCD and various diseases, as well as the underlying mechanisms. We believe that further research in this area will lead to the discovery of novel types of metal-dependent RCD, a better understanding of the underlying mechanisms, and the development of new therapeutic strategies for human diseases.

Generation of a terahertz quasi-Pearcey beam and its investigation in ptychography.

The terahertz structured beams played a significant role in imaging. We utilized the transmitter with 0.1 THz to generate the quasi-Pearcey beam. The beam is produced by combining the self-designed parabola-slit modulated plate and Fourier lens, showing stripe-shaped pattern and self-focusing property. Based on that, introducing it into the testing of ptychography, we discovered there are decent effects in field reconstruction of the probe and sample with this beam by comparisons both in the simulations and the experiments. The beam has good spatial coherence through the analysis of the spatial frequency spectrums. It suggests that the beam with such features can take advantage of rapid reconstruction in full-field imaging.

Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study.

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

Cadmium promoted LPS-induced inflammation through TLR4/IκBα/NFκ-B signaling by increasing ROS-mediated incomplete autophagy.

Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.

A nomogram based on CT texture features to predict the response of patients with advanced pancreatic cancer treated with chemotherapy.

OBJECTIVE: This study aimed to evaluate the predictive value of computed tomography (CT) texture features in the treatment response of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy. METHODS: This study enrolled 84 patients with APC treated with first-line chemotherapy and conducted texture analysis on primary pancreatic tumors. 59 patients and 25 were randomly assigned to the training and validation cohorts at a ratio of 7:3. The treatment response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). The patients were divided into progressive and non-progressive groups. The least absolute shrinkage selection operator (LASSO) was applied for feature selection in the training cohort and a radiomics signature (RS) was calculated. A nomogram was developed based on a multivariate logistic regression model incorporating the RS and carbohydrate antigen 19-9 (CA19-9), and was internally validated using the C-index and calibration plot. We performed the decision curve analysis (DCA) and clinical impact curve analysis to reflect the clinical utility of the nomogram. The nomogram was further externally confirmed in the validation cohort. RESULTS: The multivariate logistic regression analysis indicated that the RS and CA19-9 were independent predictors (P < 0.05), and a trend was found for chemotherapy between progressive and non-progressive groups. The nomogram incorporating RS, CA19-9 and chemotherapy showed favorable discriminative ability in the training (C-index = 0.802) and validation (C-index = 0.920) cohorts. The nomogram demonstrated favorable clinical utility. CONCLUSION: The RS of significant texture features was significantly associated with the early treatment effect of patients with APC treated with chemotherapy. Based on the RS, CA19-9 and chemotherapy, the nomogram provided a promising way to predict chemotherapeutic effects for APC patients.

Comparative Study on the Efficacy of Precise Radiotherapy in Lymphatic Drainage Area of Esophageal Cancer between Preventive Radiation and Invasive Field Radiation.

To investigate the efficacy of precise radiation therapy for lymphatic drainage area prevention (ENI) and invasive field irradiation (IFI) in patients with esophageal cancer undergoing radical radiotherapy. A retrospective analysis was conducted on 96 esophageal cancer patients admitted to our hospital from March 2018 to March 2021 who underwent radical radiotherapy. Among them, 48 patients who received precise radiation therapy to prevent radiation in the lymphatic drainage area were included in the ENI group, and 48 patients who received field irradiation were included in the IFI group. Compare and analyze the total clinical response rate, local control rate within 3 years after treatment, survival rate, and incidence of adverse reactions after radiotherapy between two groups of patients. There was no statistically significant difference in the total clinical response rate between the ENI group and the IFI group after radiotherapy (P > .05). There was no statistically significant difference in local control rate and survival rate between the ENI group and the IFI group within 3 years of treatment (P > .05). The incidence of postoperative complications in the ENI group was significantly higher than that in the IFI group, with a statistically significant difference (P < .05). When giving radical radiotherapy to esophageal cancer patients, the clinical total effective rate, survival rate, and local control rate of involving field irradiation are equivalent to the preventive radiation effect of precise radiotherapy for lymphatic drainage area. Besides, involving field irradiation can reduce the incidence of adverse reactions in patients after radiotherapy, which has high clinical value.

Cadmium induced immunosuppression through TLR-IκBα-NFκB signaling by promoting autophagic degradation.

Environmental and occupational exposure to cadmium (Cd) poses a serious threat to human health. Recent studies indicate that Cd perturbs the immune system and increases the risk of pathogenicity and mortality of bacterial or virus infection. However, the underlying mechanism of Cd-modulated immune responses remains unclear. In this study, we aim to investigate the role of Cd in the immune function of mouse spleen tissues and its primary T cells with Concanavalin A (ConA, a well-known T cell mitogen) activation condition, and elucidate the molecular mechanism. The results showed that Cd exposure inhibited ConA-induced the expressions of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in mouse spleen tissues. Furthermore, the transcriptomic profile by RNA-sequence reveals that: (1) Cd exposure can alter immune system process; (2) Cd may affect the NFκB signaling pathway. Both in vitro and in vivo results showed that Cd exposure reduced ConA-activated toll-like receptor 9 (TLR9)-IκBα-NFκB signaling, and the expressions of TLR9, TNF-α and IFN-γ, which were effectively reversed by autophagy-lysosomal inhibitors. All these results confirmedly demonstrated that, by promoting the autophagy-lysosomal degradation of TLR9, Cd suppressed immune response under ConA activation condition. This study provides insight on the mechanism of Cd immunnotoxicity, which might contribute to the prevention of Cd toxicity in the future.

Altered spontaneous brain activities in maintenance hemodialysis patients with cognitive impairment and the construction of cognitive function prediction models.

OBJECTIVE: The brain neuromechanism in maintenance hemodialysis patients (MHD) with cognitive impairment (CI) remains unclear. The study aimed to probe the relationship between spontaneous brain activity and CI by using resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: Here, 55 MHD patients with CI and 28 healthy controls were recruited. For baseline data, qualitative data were compared between groups using the χ2 test; quantitative data were compared between groups using the independent samples t-test, ANOVA test, Mann-Whitney U-test, or Kruskal-Wallis test. Comparisons of ALFF/fALFF/ReHo values among the three groups were calculated by using the DPABI toolbox, and then analyzing the correlation with clinical variables. p < .05 was considered a statistically significant difference. Furthermore, back propagation neural network (BPNN) was utilized to predict cognitive function. RESULTS: Compared with the MHD-NCI group, the patients with MHD-CI had more severe anemia and higher urea nitrogen levels, lower mALFF values in the left postcentral gyrus, lower mfALFF values in the left inferior temporal gyrus, and greater mALFF values in the right caudate nucleus (p < .05). The above-altered indicators were correlated with MOCA scores. BPNN prediction models indicated that the diagnostic efficacy of the model which inputs were hemoglobin, urea nitrogen, and mALFF value in the left central posterior gyrus was optimal (R2 = 0.8054), validation cohort (R2 = 0.7328). CONCLUSION: The rs-fMRI can reveal the neurophysiological mechanism of cognitive impairment in MHD patients. In addition, it can serve as a neuroimaging marker for diagnosing and evaluating cognitive impairment in MHD patients.

Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells.

Cadmium (Cd2+) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd2+ induced cytotoxicity by disrupting the intracellular Ca2+ homeostasis that is physically regulated by the endoplasmic reticulum (ER) Ca2+ store. However, the molecular mechanism of ER Ca2+ homeostasis in Cd2+-induced nephrotoxicity remains unclear. In this study, our results firstly revealed that the activation of calcium-sensing receptor (CaSR) by NPS R-467 could protect against Cd2+ exposure-induced cytotoxicity of mouse renal tubular cells (mRTEC) by restoring ER Ca2+ homeostasis through the ER Ca2+ reuptake channel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). Cd2+-induced ER stress and cell apoptosis were effectively abrogated by SERCA agonist CDN1163 and SERCA2 overexpression. In addition, in vivo, and in vitro results proved that Cd2+ reduced the expressions of SERCA2 and its activity regulator phosphorylation phospholamban (p-PLB) in renal tubular cells. Cd2+-induced SERCA2 degradation was suppressed by the treatment of proteasome inhibitor MG132, which suggested that Cd2+ reduced SERCA2 protein stability by promoting the proteasomal protein degradation pathway. These results suggested that SERCA2 played pivotal roles in Cd2+-induced ER Ca2+ imbalance and stress to contribute to apoptosis of renal tubular cells, and the proteasomal pathway was involved in regulating SERCA2 stability. Our results proposed a new therapeutic approach targeting SERCA2 and associated proteasome that might protect against Cd2+-induced cytotoxicity and renal injury.

Blocking stanniocalcin 2 reduces sunitinib resistance in clear cell renal cell carcinoma.

Stanniocalcin 2 (STC2) has been identified as a prognostic marker in renal cell carcinoma. However, the role of STC2 in renal cell carcinoma is still unclear. In this study, we investigated the relationship between high expression of STC2 and sunitinib resistance in cells and the underlying mechanism. Through GEPIA platform analysis based on TCGA database, it showed that the expression of STC2 in kidney renal clear cell carcinoma (KIRC) was significantly higher than that in the normal population. Real-time quantitative PCR and western blotting detected significantly higher expression levels of STC2 in clear cell renal cell carcinoma (ccRCC) cells than that in normal renal cells. Enzyme-linked immunosorbent assay (ELISA) determined whether there is a high secretion of STC2 in ccRCC cells. The sunitinib resistance could be significantly reduced by STC2 neutralizing antibody but aggravated by the addition of recombinant human STC2 in ccRCC cells. Sunitinib suppressed STC2 expression and secretion, destroyed lysosomal acidic pH, and accumulated in the cells. However, STC2 neutralizing antibody can reduce the accumulation of sunitinib in cells to improve the inhibitory efficiency of sunitinib on cell proliferation. This study suggested STC2 could serve as a potential novel target for the treatment of ccRCC, anti-STC2 antibody might be an option of immunotherapy in the future.

Cadmium perturbed lipid profile and induced liver dysfunction in mice through phosphatidylcholine remodeling and promoting arachidonic acid synthesis and metabolism.

Cadmium ion (Cd2+) exposure has been reported to associate with the prevalence of dyslipidemia, and contribute to the initiation and progression of nonalcoholic fatty liver disease (NAFLD). However, Cd2+ exposure perturbed specific metabolic pathways and underlying mechanisms are still unclear. In the present study, through lipidomics analyses of differential metabolites in serum between the Cd2+-exposed mice and the control group, 179 differential metabolites were identified, among which phosphatidylcholines (PCs) accounted for 49 % metabolites. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment assay indicates that PCs participate in the metabolic pathways, including the Arachidonic Acid (AA) metabolism, which also could be potential NAFLD biomarkers. Moreover, in vivo and in vitro results suggested that Cd2+ exposure induced PC synthesis and remodeling, and increased AA level by promoting fatty acid desaturase 1 (FADS1) to catalyze synthesis process instead of cytosolic phospholipase A2 (cPLA2) mediated release pathway. Inhibition of FADS1 by T3364366 could reverse Cd-induced AA, prostaglandin E2 (PGE2) and triglyceride (TAG) levels, and it also reduce cisplatin resistance in HepG2 cells. This study provides new evidence of Cd2+-induced dyslipidemia and reveals underlying molecular mechanism involved in liver dysfunction of Cd2+ exposure.

Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging to Early Detect Tissue Injury and Microcirculation Alteration in Hepatic Injury Induced by Intestinal Ischemia-Reperfusion in a Rat Model.

BACKGROUND: Intravoxel incoherent motion (IVIM) can provide quantitative information about water diffusion and perfusion that can be used to evaluate hepatic injury, but it has not been studied in hepatic injury induced by intestinal ischemia-reperfusion (IIR). Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can provide perfusion data, but it is unclear whether it can provide useful information for assessing hepatic injury induced by IIR. PURPOSE: To examine whether IVIM and DCE-MRI can detect early IIR-induced hepatic changes, and to evaluate the relationship between IVIM and DCE-derived parameters and biochemical indicators and histological scores. STUDY TYPE: Prospective pre-clinical study. POPULATION: Forty-two male Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: IVIM-diffusion-weighted imaging (DWI) using diffusion-weighted echo-planar imaging sequence and DCE-MRI using fast spoiled gradient recalled-based sequence at 3.0 T. ASSESSMENT: All rats were randomly divided into the control group (Sham), the simple ischemia group, the ischemia-reperfusion (IR) group (IR1h, IR2h, IR3h, and IR4h) in a model of secondary hepatic injury caused by IIR, and IIR was induced by clamping the superior mesenteric artery for 60 minutes and then removing the vascular clamp. Advanced Workstation (AW) 4.6 was used to calculate the imaging parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], perfusion-related diffusion [D* ] and volume fraction [f]) of IVIM. OmniKinetics (OK) software was used to calculate the DCE imaging parameters (Ktrans , Kep , and Ve ). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with an automatic biochemical analyzer. Superoxide dismutase (SOD) activity was assessed using the nitro-blue tetrazolium method. Malondialdehyde (MDA) was determined by thiobarbituric acid colorimetry. Histopathology was performed with hematoxylin and eosin staining. STATISTICAL TESTS: One-way analysis of variance (ANOVA) and Bonferroni post-hoc tests were used to analyze the imaging parameters and biochemical indicators among the different groups. Pearson correlation analysis was applied to determine the correlation between imaging parameters and biochemical indicators or histological score. RESULTS: ALT and MDA reached peak levels at IR4h, while SOD reached the minimum level at IR4h (all P < 0.05). ADC, D, D* , and f gradually decreased as reperfusion continued, and Ktrans and Ve gradually increased (all P < 0.05). The degrees of change for f and Ve were greater than those of other imaging parameters at IR1h (all P < 0.05). All groups showed good correlation between imaging parameters and SOD and MDA (r[ADC] = 0.615, -0.666, r[D] = 0.493, -0.612, r[D* ] = 0.607, -0.647, r[f] = 0.637, -0.682, r[Ktrans ] = -0.522, 0.500, r[Ve ] = -0.590, 0.665, respectively; all P < 0.05). However, the IR groups showed poor or no correlation between the imaging parameters and SOD and MDA (P [Ktrans and MDA] = 0.050, P [D and SOD] = 0.125, P [the remaining imaging parameters] < 0.05). All groups showed a positive correlation between histological score and Ktrans and Ve (r = 0.775, 0.874, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.739, -0.821, -0.868, -0.841, respectively; all P < 0.05). For the IR groups, there was a positive correlation between histological score and Ktrans and Ve (r = 0.747, 0.802, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.567, -0.712, -0.715, -0.779, respectively; all P < 0.05). DATA CONCLUSION: The combined application of IVIM and DCE-MRI has the potential to be used as an imaging tool for monitoring IIR-induced hepatic histopathology. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Oxygen vacancy-rich 2D/0D BiO1-XBr/AgBr Z-scheme photocatalysts for efficient visible light driven degradation of tetracycline.

Semiconductor-based photocatalytic technology, as a green and promising avenue in response to the abuse of antibiotic pollution and human health crisis, is restricted by the limited photo-absorption and fast recombination of photogenerated carriers. In this paper, all these challenges were settled by AgBr particles incorporated into oxygen-deficient BiOBr nanosheets, forming novel oxygen vacancy (OV)-rich 2D/0D Z-scheme heterojunctions. Z-scheme photocatalytic system has an effective separation rate of photogenerated carriers and an ability to maintain original redox capacity. Moreover, introducing OVs in the Z-scheme can not only improve the visible light absorption ability, but also serve as recombination centers, thus promoting the separation of electrons and holes. Notably, the photocatalytic activity of 2D/0D BiO1-XBr/AgBr (2:1) was significantly improved under the irradiation of visible light, removing 81% of tetracycline after 25 min, which was about 2.62 times and 2.03 times as high as those of BiO1-XBr and AgBr, respectively. In addition, the 2D/0D BiO1-XBr/AgBr (2:1) indicated high photocatalytic stability and reusability, and its tetracycline degradation efficiency remained stable after five cycles. In summary, this work suggests that the photocatalysts have a great potential to remove TC and provides a possible strategy for purifying water.

Line imaging of a terahertz zero-order Mathieu-Gauss beam.

Thestudy of terahertz (THz) structured beams has become an interesting subject. Here, we use 3D printed diffractive plates to generate a THz zero-order Mathieu-Gauss beam at a frequency of 0.1 THz and simulate its line-imaging effect. According to the nondiffraction property of the beam, we conduct a transmission imaging test by placing the imaging plate at different positions along the direction of beam propagation. The results show that the THz zero-order Mathieu-Gauss beam has a good imaging effect in the depth of field of about 130-380 mm. This can be used in large depth of field THz line imaging.

A novel urine cell-free DNA preservation solution and its application in kidney transplantation.

AIM: Urine cell-free DNA (cfDNA) is a new type of liquid biopsy biomarker used in tumours and allograft injury detection but is highly susceptible to degradation by the high nuclease activity of urine. This study presents a newly developed urine cfDNA preservation solution (AlloU), efficient for examining allograft injury in kidney transplant recipients (KTx). METHODS: We established urine-preserve solution called AlloU based on the response-surface methodology, with two commercial collection reagents (Streck and K2 EDTA preservation solution) included for analysis. A total of 120 urine samples from KTx patients, including morning, nocturnal and random urine from specific storage time were subjected to investigation. The urine total cfDNA concentration was quantified by fluorometry, fragment distribution was analysed by qPCR, and donor-derived cfDNA (ddcfDNA) was detected by next-generation sequencing. RESULTS: Urine total cfDNA concentration and fragment size of samples preserved with AlloU and Streck did not change significantly within 5 days whereas the ddcfDNA also did not change significantly within 7 days. However, compared with EDTA, the total cfDNA concentration increased significantly on the third day. When compare with different urine types, it was found that samples preserved with AlloU showed no significant differences in total cfDNA concentration, fragment size, and ddcfDNA concentration, however, the SD for morning urine was significantly smaller in total cfDNA and ddcfDNA concentration. CONCLUSION: To the best of our knowledge, this is the first report to verify the dynamics of urine cfDNA in KTx, especially in the analysis impact of different urine types on cfDNA detection.

The application of oncolytic viruses in cancer therapy.

Oncolytic therapy is a treatment method used to directly combat tumor cells by modifying the genes of naturally occurring low pathogenic viruses to form "rhizobia" virus. By taking the advantage of abnormal signal pathways in cancer cells, it selectively replicates in tumor cells leading to tumor cell lysis and death. At present, clinical studies widely employ biomolecular technology to transform oncolytic viruses to exert stronger oncolytic effects and reduce their adverse reactions. This review summarizes the current progresses and the molecular mechanism of oncolytic viruses towards tumor treatment and management.

Dysregulation of autophagy acts as a pathogenic mechanism of non-alcoholic fatty liver disease (NAFLD) induced by common environmental pollutants.

Non-alcoholic fatty liver disease (NAFLD) has been the most common chronic liver disease in the world, including the developing countries. NAFLD is metabolic disease with significant lipid deposition in the hepatocytes of the liver, which is usually associated with oxidative stress, inflammation and fibrogenesis, and insulin resistance. Progressive NAFLD can develop into non-alcoholic steatohepatitis (NASH) or hepatocellular carcinoma. The current evidence proposes that environmental pollutants promote development and progression of NAFLD, and autophagy plays a vital role but is multifactorial affected in NAFLD. In this review, we analyzed on the regulations of common environmental pollutants on autophagy in NAFLD. To clarify the involved roles of autophagy, we discussed the dysregulation of autophagy by environmental pollutants in adipose tissue and gut, and their interactions with liver, as well as epigenetic regulation on autophagy by environmental pollutants. Furthermore, protective roles of potential therapeutic treatments on the multiple-hits of autophagy in NAFLD were descripted.

Cadmium induces epithelial-mesenchymal transition and migration of renal cancer cells by increasing PGE2 through a cAMP/PKA-COX2 dependent mechanism.

Environmental or occupational exposure of Cadmium (Cd) is concerned to be a threat to human health. The kidney is main target of Cd accumulation, which increases the risk of renal cell carcinoma (RCC). In addition, low content of Cd had been determined in kidney cancer, however, the roles of presence of Cd in renal tumors progression are still unclear. The present study is proposed to determine the effect of low-dose Cd exposure on the renal cancer cells and aimed to clarify the underlying mechanisms. The cell viability, cytotoxicity, and the migratory effect of low-dose Cd on the renal cancer cells were detected. Moreover, the roles of reactive oxygen species (ROS), Ca2+, and cyclic AMP (cAMP)/protein kinase A (PKA)-cyclooxygenase2 (COX2) signaling, as well as COX2 catalytic product prostaglandin E2 (PGE2) on cell migration and invasion were identified. Our results suggested that low dose Cd exposure promoted migration of renal cancer Caki-1 cells, which was not dependent on Cd-induced ROS and intracellular Ca2+ levels. Cd exposure induced cAMP/PKA-COX2, which mediated cell migration and invasion, and decreased expressions of epithelial-mesenchymal transition (EMT) marker, E-cadherin, but increased expressions of N-cadherin and Vimentin. Moreover, Cd-induced secretion of PGE2 feedback on activation of cAMP/PKA-COX2 signaling, also promoted EMT, migration and invasion of renal cancer Caki-1 cells. This study might contribute to understanding of the mechanism of Cd-induce progression of renal cancer and future studies on the prevention and therapy of renal cell carcinomas.

Enhanced computed tomography radiomics-based machine-learning methods for predicting the Fuhrman grades of renal clear cell carcinoma.

OBJECTIVE: To develop and test an optimal machine learning model based on the enhanced computed tomography (CT) to preoperatively predict pathological grade of clear cell renal cell carcinoma (ccRCC). METHODS: A retrospective analysis of 53 pathologically confirmed cases of ccRCC was performed and 25 consecutive ccRCC cases were selected as a prospective testing set. All patients underwent routine preoperative abdominal CT plain and enhanced scans. Renal tumor lesions were segmented on arterial phase images and 396 radiomics features were extracted. In the training set, seven discrimination classifiers for high- and low-grade ccRCCs were constructed based on seven different machine learning models, respectively, and their performance and stability for predicting ccRCC grades were evaluated through receiver operating characteristic (ROC) analysis and cross-validation. Prediction accuracy and area under ROC curve were used as evaluation indices. Finally, the diagnostic efficacy of the optimal model was verified in the testing set. RESULTS: The accuracies and AUC values achieved by support vector machine with radial basis function kernel (svmRadial), random forest and naïve Bayesian models were 0.860±0.158 and 0.919±0.118, 0.840±0.160 and 0.915±0.138, 0.839±0.147 and 0.921±0.133, respectively, which showed high predictive performance, whereas K-nearest neighborhood model yielded lower accuracy of 0.720±0.188 and lower AUC value of 0.810±0.150. Additionally, svmRadial had smallest relative standard deviation (RSD, 0.13 for AUC, 0.17 for accuracy), which indicates higher stability. CONCLUSION: svmRadial performs best in predicting pathological grades of ccRCC using radiomics features computed from the preoperative CT images, and thus may have high clinical potential in guiding preoperative decision.

[Endometrial Injury and Preservation after Magnetic Resonance-guided Focused Ultrasound Ablation of Uterine Fibroids].

Objective To explore the risk factors for incident endometrial injury and 3-month endometrial injury after magnetic resonance-guided focused ultrasound(MRgFUS)ablation of uterine fibroids(UF). Methods UF patients who were diagnosed in Peking Union Medical College Hospital and underwent MRgFUS ablation in Amcare Women's and Children's Hospital from August 2016 to October 2020 were retrospectively enrolled in this study.Clinical data of 66 UF patients were collected and compared between endometrial injury group and non-injury group.Stepwise regression was employed to determine the risk factors for the incident endometrial injury and 3-month endometrial injury.Multivariate logistic regression analysis was performed to explore the relationship of endometrial injury with age,pre-ablation tumor size,multiple UF,International Federation of Gynecology and Obstetrics(FIGO)classification,T2WI signal intensity,and treatment time.Results In terms of incident endometrial injury,the 66 patients included 41(62.1%)cases with no injury,4 cases(6.1%) with grade 1 injury,5 cases(7.6%)with grade 2 injury,and 16 cases(24.2%)with grade 3 injury.In terms of 3-month endometrial injury,the 66 patients included 49 cases(74.2%)with no injury,5 cases(7.6%)with grade 1 injury,2 cases(3.0%)with grade 2 injury,and 10 cases(15.2%)with grade 3 injury.Stepwise regression analysis indicated that FIGO classification was significantly associated with incident endometrial injury(B=-0.121,SE=0.045,ß=-0.326,t=-2.670,P=0.010)and 3-month endometrial injury(B=-0.125,SE=0.042,ß=-0.375,t=-2.989,P=0.004).Multivariate logistic regression analysis showed that FIGO classification was an independent risk factor for incident endometrial injury[OR=0.518(0.307-0.873),P=0.014]and 3-month endometrial injury[OR=0.456(0.253-0.824),P=0.009].Conclusions Endometrial injury could be controlled after MRgFUS ablation of UF and recover to some extent after 3 months.FIGO classification was an independent risk factor for both incident and 3-month endometrial injury.