[Effects of PM2.5 and O3 sub-chronic combined exposure on ATP amount and ATPase activities in rat nasal mucosa].

OBJECTIVE: To evaluate the effects of fine particle matter (PM2.5) and ozone (O3) combined exposure on adenosine triphosphate (ATP) amount and ATPase activities in nasal mucosa of Sprague Dawley (SD) rats. METHODS: Twenty male SD rats were divided into control group (n=10) and exposure group (n=10) by random number table method. The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team, respectively, and exposed for 208 d. During the exposure period, the concentrations of PM2.5 and O3 in the exposure system were monitored, and a comprehensive assessment of PM2.5 and O3 in the exposure system was conducted by combining self-measurement and site data. On the 208 d of exposure, the core, liver, spleen, kidney, testis and other major organs and nasal mucosal tissues of the rats were harvested. Each organ was weighed and the organ coefficient calculated. The total amount of ATP was measured by bioluminescence, and the activities of Na+-K+ -ATPase and Ca2+ -ATPase were detected by spectrophotometry. The t test of two independent samples was used to compare the differences among the indicator groups. RESULTS: From the 3rd week to the end of exposure duration, the body weight of the rats in the exposure group was higher than that in the control group (P < 0.05), and there was no significant difference in organ coefficients between the two groups. The average daily PM2.5 concentration in the exposure group was (30.68±19.23) µg/m3, and the maximum 8 h ozone concentration (O3-8 h) was (82.45±35.81) µg/m3. The chemiluminescence value (792.4±274.1) IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group (1 126.8±218.1) IU/L. The Na+-K+-ATPase activity (1.53±0.85) U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group (4.31±1.60) U/mg (P < 0.05). The protein content of nasal mucosa in the control group and the exposure group were (302.14±52.51) mg/L and (234.58±53.49) mg/L, respectively, and the activity of Ca2+-ATPase was (0.81±0.27) U/mg and (0.99±0.73) U/mg, respectively. There was no significant difference between the groups. CONCLUSION: The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2.5 and O3.

Management of Nontraumatic Spontaneous Renal Hemorrhage (Wünderlich Syndrome) through Robotic-Assisted Laparoscopic Nephrectomy: A Case Series.

BACKGROUND Wünderlich syndrome (WS) is a rare diagnosis of nontraumatic spontaneous renal hemorrhage into the subcapsular, perirenal, or pararenal spaces. Prompt and effective intervention is necessary for an accurate pathological diagnosis and preservation of life. In the current literature, open surgery is the primary option when conservative treatment fails, but there can be serious trauma and corresponding consequences. Herein, we present 3 cases of Wünderlich syndrome managed by robot-assisted laparoscopic nephrectomy via a retroperitoneal approach. CASE REPORT Patient 1 was a 44-year-old woman with right flank pain for 6 h. Patient 2 was a 53-year-old woman with a history of diabetes who had pain in her right flank pain and nausea for 1 day. Patient 3 was a 45-year-old man with left flank pain for 1 day. All cases of WS were confirmed by CT. All 3 patients were treated with retroperitoneal robot-assisted nephrectomy after conservative treatment failed. Pathological examination confirmed that patient 1 had angiomyolipoma, and patients 2 and 3 had renal clear cell carcinoma. At the 9-month follow-up, renal function was good and no evidence of recurrence or metastasis has been detected. CONCLUSIONS These cases have highlighted the importance of the clinical history and imaging findings in the diagnosis of Wünderlich syndrome, and show that rapid management can be achieved using robot-assisted laparoscopic nephrectomy. However, it is crucial to have a skilled surgical team and adequate preoperative preparation.

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Relationships between blood chromium exposure and liver injury: Exploring the mediating role of systemic inflammation in a chromate-exposed population.

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.

A rapid identification method for soft tissue markers of dentofacial deformities based on heatmap regression.

OBJECTIVE: The purpose of this study was to construct a facial deformity dataset and a network model based on heatmap regression for the recognition of facial soft tissue landmarks to provide a basis for clinicians to perform cephalometric analysis of soft tissue. MATERIALS AND METHODS: A 34-point face marker detection model, the Back High-Resolution Network (BHR-Net), was constructed based on the heatmap regression algorithm, and a custom dataset of 1780 facial detection images for orthognathic surgery was collected. The mean normalized error (MNE) and 10% failure rate (FR10%) were used to evaluate the performance of BHR-Net, and a test set of 50 patients was used to verify the accuracy of the landmarks and their measurement indicators. The test results were subsequently validated in 30 patients. RESULTS: Both the MNE and FR10% of BHR-Net were optimal compared with other models. In the test set (50 patients), the accuracy of the markers excluding the nose root was 86%, and the accuracy of the remaining markers reached 94%. In the model validation (30 patients), using the markers detected by BHR-Net, the diagnostic accuracy of doctors was 100% for Class II and III deformities, 100% for the oral angle plane, and 70% for maxillofacial asymmetric deformities. CONCLUSIONS: BHR-Net, a network model based on heatmap regression, can be used to effectively identify landmarks in maxillofacial multipose images, providing a reliable way for clinicians to perform cephalometric measurements of soft tissue objectively and quickly.

Potential mechanisms of lung injury and repair after hexavalent chromium [Cr(VI)] aerosol whole-body dynamic exposure.

Hexavalent chromium [Cr(VI)], known as "Top Hazardous Substances", poses a significant threat to the respiratory system. Nevertheless, the potential mechanisms of toxicity and the lung's repair ability after injury remain incompletely understood. In this study, Cr(VI) aerosol whole-body dynamic exposure system simulating real exposure scenarios of chromate workers was constructed to evaluate the lung injury and repair effects. Subsequently, miRNA sequencing, mRNA sequencing and metabolomics analyses on lung tissue were performed to explore the underlying mechanisms. Our results revealed that Cr(VI) exposure led to an increase in lactic dehydrogenase activity and a time-dependent decline in lung function. Notably, after 13 w of Cr(VI) exposure, alveolar hemorrhage, thickening of alveolar walls, emphysema-like changes, mitochondrial damage of alveolar epithelial cells and macrophage polarization changes were observed. Remarkably, a two-week repair intervention effectively ameliorated lung function decline and pulmonary injury. Furthermore, significant disruptions in the expressions of miRNAs and mRNAs involved in oxidative phosphorylation, glycerophospholipid metabolism and inflammatory signaling pathways were found. The two-week repair period resulted in the reversal of expression of oxidative phosphorylation related genes, and inhibited the inflammatory signaling pathways. This study concluded that the inhibition of the mitochondrial oxidative phosphorylation pathway and the subsequent enhancement of inflammatory response might be key mechanisms underlying Cr(VI) pulmonary toxicity, and timely cessation of exposure could effectively alleviate the pulmonary injury. These findings shed light on the potential mechanisms of Cr(VI) toxicity and provide crucial insights into the health protection for occupational populations exposed to Cr(VI).

Circ_0061140 Potentiates Clear Cell Renal Cell Carcinoma Progression Via the MicroRNA-126-5p/ADAM9 Axis.

Circular RNAs (circRNAs) function as new cancer biomarkers, but the role of circ_0061140 remains unknown in clear cell renal cell carcinoma (ccRCC). Therefore, we aimed to validate the functions of circ_0061140 in ccRCC and its potential as a prognostic biomarker. At first, circ_0061140 expression in ccRCC tissues and cells was detected, and circ_0061140 was upregulated in ccRCC tissues (p < 0.0001) and cells (p < 0.0001). Patients with high expression of circ_0061140 had a worse prognosis (p < 0.05). Then, siRNA against circ_0061140 was transfected into Caki-1 and UT14 cells to explore its roles in the biological functions of ccRCC cells, and suppressing roles of downregulated circ_0061140 were observed in the cell growth of Caki-1 and UT14 cells (p < 0.01). Next, circ_0061140 was found to be a sponge of miR-126-5p, and ADAM9 was determined to be a target of miR-126-5p. Finally, functional rescue experiments were conducted to observe their roles in ccRCC cell growth. It was suggested that suppressed miR-126-5p or overexpressed ADAM9 induced cell proliferation and restricted cell apoptosis in ccRCC cells based on si-circ_0061140 (p < 0.01). Altogether, this study highlights that circ_0061140 plays an oncogenic role in ccRCC through modulation of the miR-126-5p/ADAM9 axis.

Pediatric Mycotic Pseudoaneurysm of the Ascending Aorta: A Case Report.

Mycotic pseudoaneurysm of the ascending aorta is extremely uncommon, particularly in children with no prior cardiac surgery or trauma. We report a rare case of a mycotic pseudoaneurysm of the ascending aorta in a 2-year-old girl with no history of cardiac surgery. Investigations revealed a methicillin-resistant Staphylococcus aureus infection and significant pericardial effusion in the child who presented with persistent fever and altered mental state. Cardiac ultrasound revealed a disruption in the aortic wall and a tumor-like structure. Contrast-enhanced computed tomography confirmed an ascending aortic pseudoaneurysm with thrombus. The child underwent successful surgical treatment without implants. This case emphasizes the diagnostic significance of imaging, particularly the advantages of ultrasound in pediatric settings, and the need for timely and accurate diagnosis using appropriate imaging modalities in children.

From WSI-level to patch-level: Structure prior-guided binuclear cell fine-grained detection.

Accurate and quick binuclear cell (BC) detection plays a significant role in predicting the risk of leukemia and other malignant tumors. However, manual counting of BCs using microscope images is time consuming and subjective. Moreover, traditional image processing approaches perform poorly due to the limitations in staining quality and the diversity of morphological features in binuclear cell (BC) microscopy whole-slide images (WSIs). To overcome this challenge, we propose a multi-task method inspired by the structure prior of BCs based on deep learning, which cascades to implement BC coarse detection at the WSI level and fine-grained classification at the patch level. The coarse detection network is a multitask detection framework based on circular bounding boxes for cell detection and central key points for nucleus detection. Circle representation reduces the degrees of freedom, mitigates the effect of surrounding impurities compared to usual rectangular boxes and can be rotation invariant in WSIs. Detecting key points in the nucleus can assist in network perception and be used for unsupervised color layer segmentation in later fine-grained classification. The fine classification network consists of a background region suppression module based on color layer mask supervision and a key region selection module based on a transformer due to its global modeling capability. Additionally, an unsupervised and unpaired cytoplasm generator network is first proposed to expand the long-tailed distribution dataset. Finally, experiments are performed on BC multicenter datasets. The proposed BC fine detection method outperforms other benchmarks in almost all evaluation criteria, providing clarification and support for tasks such as cancer screenings.

Modified hood technique for single-port robot-assisted radical prostatectomy contributes to early recovery of continence.

Background and purpose: Urinary incontinence is one of the common side effects of robot-assisted radical prostatectomy (RARP). Here, we described the modified Hood technique for single-port RARP (sp-RARP) and assessed the interest of this new technique for early continence recovery. Methods: We retrospectively reviewed 24 patients who underwent sp-RARP modified hood technique from June 2021 to December 2021. The pre-and intraoperative variables, postoperative functional and oncological outcomes of patients were collected and analyzed. The continence rates were estimated at 0 day, 1 week, 4 weeks, 3 months and 12 months after catheter removal. Continence was defined as wearing no pad over a 24 h period. Results: Mean time of operation and estimated blood loss were 183 min and 170 ml, respectively. The postoperative continence rates at 0 day, 1 week, 4 weeks, 3 months and 12 months after catheter removal were 41.7%, 54.2%, 75.0%, 91.7% and 95.8%, respectively. There were two patients who detected positive surgical margins and no patients observed complications requiring further treatment. Conclusion: The modified hood technique is a safe and feasible method that provides better outcomes in terms of early return of continence, without increasing estimated blood loss and compromising oncologic outcomes.

[Observation of early clinical efficacy of unilateral biportal endoscopy technique in the treatment of lumbar postoperative adjacent segmental diseases].

OBJECTIVE: To investigate early clinical efficacy of unilateral biportal endoscopy technique for the treatment of lumbar postoperative adjacent segmental diseases. METHODS: Fourteen patients with lumbar postoperative adjacent segmental diseases were treated with unilateral biportal endoscopy technique from June 2019 to June 2020. Among them, there were 9 males and 5 females, aged from 52 to 73 years old, and the interval between primary and revision operations ranged from 19 to 64 months. Adjacent segmental degeneration occurred after lumbar fusion in 10 patients and after lumbar nonfusion fixation in 4 patients. All the patients received unilateral biportal endoscopy assisted posterior unilateral lamina decompression or unilateral approach to the contralateral decompression. The operation time, postoperative hospital stay and complications were observed. The visual analogue scale (VAS) of low back pain and leg pain, Oswestry Disability Index (ODI), modified Japanese Orthopaedic Association (mJOA) score were recorded before operation and at 3 days, 3 months, and 6 months after operation. RESULTS: All procedures were successfully completed. Surgical duration ranged from 32 to 151 min. Postoperative CT showed adequate decompression and preservation of most joints. Out of bed walking 1 to 3 days after surgery, postoperative hospital stay was 1 to 8 days, and postoperative follow-up was 6 to 11 months. All 14 patients returned to normal life within 3 weeks after surgery, and VAS, ODI, and mJOA scores improved significantly at 3 days and 3, 6 months after surgery. One patient occurred cerebrospinal fluid leak after operation, received local compression suture, and the wound healed after conservative treatment. One patient occurred postoperative cauda equina neurologic deficit, which was gradually recovered about 1 month after rehabilitation therapy. One patients advented transient pain of lower limbs after surgery, and the symptoms were relieved after 7 days of treatment with hormones, dehydration drugs and symptomatic management. CONCLUSION: Unilateral biportal endoscopy technique has a good early clinical efficacy in the treatment of lumbar postoperative adjacent segmental diseases, which may provide a new minimally invasive, non-fixation option for the treatment of adjacent segment disease.

Relationship between systemic inflammation and lung injury induced by chromate exposure: A cross-sectional study in workers.

Hexavalent chromium [Cr(VI)] compounds, known as "Group I Human Carcinogen" and "Category I Respiratory Sensitizer", posed great challenges to the respiratory system. A cross-sectional study was undertaken among chromate workers. Serum club cell protein 16 (CC16) and soluble urokinase-type plasminogen activator receptor (suPAR) were measured using ELISA. Thirteen macrophage-related mediators were tested using cytometric bead array. After controlling for sex, age, smoking status, drinking status and BMI, each increase of one-unit of Ln-transformed blood Cr was related to the increase of IL-1beta [Beta (95% CI), 7.22(1.14, 13.29)%, P = 0.021], IL-23 [8.5(1.15, 15.85)%, P = 0.021], IFN-gamma [3.14(0.15, 6.13)%, P = 0.040], and suPAR [9.31(2.5, 16.12) %, P = 0.008], as well as the increase of CC16 by 3.88(0.42, 7.34) % (P = 0.029). Moreover, these inflammatory mediators played an mediation role in the rise of CC16 caused by Cr(VI). The exposure-response curve analysis revealed a substantial nonlinear association of IFN-gamma and suPAR with CC16, thus the mediation effect of INF-gamma and suPAR required cautious interpretation. The positive connection between macrophage-related mediators was stronger in the high exposure group than in the low exposure group, suggesting that high concentration of chromate might promote a complex interplay within the immune system.

Two-week repair alleviates hexavalent chromium-induced hepatotoxicity, hepatic metabolic and gut microbial changes: A dynamic inhalation exposure model in male mice.

Hexavalent chromium [Cr(VI)] has been identified as a "Group I human carcinogen" with multisystem and multiorgan toxicity. A dynamic inhalation exposure model in male mice, coupled with the hepatic metabolome and gut microbiome, was used to explore hepatotoxicity, and hepatic metabolic and gut microbial changes under the exposure scenarios in the workspace and general environment. The present study set up an exposure group (EXP) that inhaled 150 µg Cr/m3 for 13 weeks, a control group (CONT) that inhaled purified air, as well as a two-week repair group (REXP) after 13 weeks of exposure and the corresponding control group (RCONT). Cr(VI) induced elevation of hepatic Cr accumulation, the ratio of ALT and AST, and folate in serum. Inflammatory infiltration in the liver and abnormal mitochondria in hepatocytes were also induced by Cr(VI). Glutathione, ascorbate, folic acid, pantetheine, 3'-dephospho-CoA and citraconic acid were the key metabolites affected by Cr(VI) that were associated with significant pathways such as pantothenate and CoA biosynthesis, hypoxia-inducible factor-1 signaling pathway, antifolate resistance, alpha-linolenic acid metabolism and one carbon pool by folate. g_Allobaculum was identified as a sensitive biomarker of Cr(VI) exposure because g_Allobaculum decreased under Cr(VI) exposure but increased after repair. The gut microbiota might be involved in the compensation of hepatotoxicity by increasing short-chain fatty acid-producing bacteria, including g_Lachnospiraceae_NK4A136_group, g_Blautia, and f_Muribaculaceae. After the two-week repair, the differential metabolites between the exposed and control groups were reduced from 73 to 29, and the KEGG enrichment pathways and differential microbiota also decreased. The mechanism for repair was associated with reversion of lipid peroxidation and energy metabolism, as well as activation of protective metabolic pathways, such as the AMPK signaling pathway, longevity regulating pathway, and oxidative phosphorylation. These findings might have theoretical and practical implications for better health risk assessment and management.

How many cases are required to achieving early proficiency in purely off-clamp robot-assisted partial nephrectomy?

Background and purpose: Off-clamp robot-assisted partial nephrectomy (Offc-RAPN) is a technically challenging procedure that can effectively avoid renal ischemia owing to the absence of hilar vessel preparation and clamping. However, data on the learning curve (LC) for this technique are limited. The purpose of this study was to assess the LC of Offc-RAPN and compare the perioperative outcomes between different learning phases. Methods: This retrospective study included 50 consecutive patients who underwent purely Offc-RAPN between January 2022 and April 2023. Multidimensional cumulative sum (CUSUM) analysis method was used to assess LC. Spearman's correlation and LOWESS analysis were performed to analyze the continuous variables of perioperative outcomes. Baseline characteristics and perioperative outcomes were compared using χ2-test, t-test and U-test. Results: CUSUM analysis identified two LC phases: phase I (the first 24 cases) and phase II (the subsequent 26 cases). Phase II showed significant reductions in mean operative time (133.5 vs. 115.31 min; p = 0.04), mean console time (103.21 vs. 81.27 min; p = 0.01), and mean postoperative length of stay (5.33 vs. 4.30 days; p = 0.04) compared to phase I. However, no significant differences were observed in other perioperative outcomes or baseline characteristics between the two LC phases. Conclusions: Offc-RAPN performed by a surgeon with experience in laparoscopic and robotic surgeries achieved early proficiency in 24 cases. Moreover, Offc-RAPN alone is safe and feasible even in the initial phase of the LC for an experienced surgeon.

Long Non-Coding RNA Expression Profile Alteration Induced by Titanium Dioxide Nanoparticles in HepG2 Cells.

The liver is considered the major target organ affected by oral exposure to titanium dioxide nanoparticles (TiO2 NPs), but the mechanism of hepatotoxicity is not fully understood. This study investigated the effect of TiO2 NPs on the expression profile of long non-coding RNA (lncRNA) in hepatocytes and tried to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. The human hepatocellular carcinoma cells (HepG2) were treated with TiO2 NPs at doses of 0-200 µg/mL for 48 h and then RNA sequencing was implemented. The differential lncRNAs between the control and TiO2 NPs-treated groups were screened, then the lncRNA-mRNA network and enrichment pathways were analyzed via multivariate statistics. As a result, 46,759 lncRNAs were identified and 129 differential lncRNAs were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the targeted mRNAs of those differential lncRNAs were enriched in the Hedgehog signaling pathway, Vasopressin-regulated water reabsorption, and Glutamatergic synapse. Moreover, two lncRNA-mRNA networks, including lncRNA NONHSAT256380.1-JRK and lncRNA NONHSAT173563.1-SMIM22, were verified by mRNA detection. This study demonstrated that an alteration in the lncRNA expression profile could be induced by TiO2 NPs and epigenetics may play an important role in the mechanism of hepatotoxicity.

Genetic damage and potential mechanism exploration under different air pollution patterns by multi-omics.

Ambient air pollution was classified as carcinogenic to humans (Group 1) for lung cancer. DNA damage was an important first step in the process of carcinogenesis, and could also be induced by air pollution. In this study, intratracheal instillation and real-time air exposure system were combined to establish SHP (short-term high-level PM2.5) and LLPO (long-term low-level PM2.5 and O3) exposure patterns, respectively. Hierarchical levels of genetic biomarkers were analyzed to explore DNA damage effects in rats. Representative DNA repair genes from different repair pathways were selected to explore the relative expression levels. The methylation level of differentially expressed repair genes were also determined. Besides, miRNA sequencing and non-targeted metabolomic analysis were performed in rat lungs. KEGG and multi-omics analysis were used to explore the potential mechanism of genetic damage under different air pollution patterns. We found that LLPO exposure induced DSBs and chromosome damage. SHP exposure could induce DSBs and DNA oxidative damage, and the effects of genetic damage under this pollution pattern could be repaired by natural repair. Repair genes involved in two pattern were different. SHP exposure could induce higher methylation levels of RAD51, which might be a potential epigenetic mechanism for high-level PM2.5 induced down-regulated expression of RAD51 and DSBs. Besides, 29 overlapped alterations in metabolic pathways were identified by metabolomic and miRNA sequencing, including purine metabolism and pyrimidine metabolism after LLPO exposure. Differential miRNAs expression in lung tissue were associated with apoptosis, DNA damage and damage repair. We concluded that under different air pollution patterns, DNA damage biomarkers and activated targets of DNA damage repair network were both different. The genetic damage effects caused by high-level short-term PM2.5 can be alleviated by natural repair. We provided possible mechanisms by multi-omics which could explain the increased carcinogenic risk caused by air pollution.

DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles.

The genotoxicity of nanomaterials has attracted great attention in recent years. As a possible occupational carcinogen, the genotoxic effects and underlying mechanisms of titanium dioxide nanoparticles (TiO2 NPs) have been of particular concern. In this study, the effect of TiO2 NPs (0, 25, 50 and 100 µg/mL) on DNA damage and the role of oxidative stress were investigated using human bronchial epithelial cells (BEAS-2B) as an in vitro model. After detailed characterization, the cytotoxicity of TiO2 NPs was detected. Through transmission electron microscopy (TEM), we found that TiO2 NPs entered the cytoplasm but did not penetrate deep into the nucleus of cells. The intracellular levels of reactive oxygen species (ROS) significantly increased in a dose-dependent manner and the ratios of GSH/GSSG also significantly decreased. The results of the normal comet assay were negative, while the Fpg-modified comet assay that specifically detected DNA oxidative damage was positive. Meanwhile, N-acetyl-L-cysteine (NAC) intervention inhibited the oxidative stress and genotoxicity induced by TiO2 NPs. Therefore, it was suggested that TiO2 NPs could induce cytotoxicity, oxidative stress and DNA oxidative damage in BEAS-2B cells. DNA oxidative damage may be a more sensitive genetic endpoint to detect the genotoxicity of TiO2 NPs.

Screening of Serum Biomarkers of Coal Workers' Pneumoconiosis by Metabolomics Combined with Machine Learning Strategy.

Pneumoconiosis remains one of the most serious global occupational diseases. However, effective treatments are lacking, and early detection is crucial for disease prevention. This study aimed to explore serum biomarkers of occupational coal workers' pneumoconiosis (CWP) by high-throughput metabolomics, combining with machine learning strategy for precision screening. A case-control study was conducted in Beijing, China, involving 150 pneumoconiosis patients with different stages and 120 healthy controls. Metabolomics found a total of 68 differential metabolites between the CWP group and the control group. Then, potential biomarkers of CWP were screened from these differential metabolites by three machine learning methods. The four most important differential metabolites were identified as benzamide, terazosin, propylparaben and N-methyl-2-pyrrolidone. However, after adjusting for the influence of confounding factors, including age, smoking, drinking and chronic diseases, only one metabolite, propylparaben, was significantly correlated with CWP. The more severe CWP was, the higher the content of propylparaben in serum. Moreover, the receiver operating characteristic curve (ROC) of propylparaben showed good sensitivity and specificity as a biomarker of CWP. Therefore, it was demonstrated that the serum metabolite profiles in CWP patients changed significantly and that the serum metabolites represented by propylparaben were good biomarkers of CWP.

Advances in genotoxicity of titanium dioxide nanoparticles in vivo and in vitro.

Titanium dioxide nanoparticles (TiO2 NPs) are currently one of the most widely used nanomaterials. Due to an increasing scope of applications, the exposure of humans to TiO2 NP is inevitable, such as entering the body through the mouth with food additives or drugs, invading the damaged skin with cosmetics, and entering the body through the respiratory tract during the process of production and handling. Compared with TiO2 coarse particles, TiO2 NPs have stronger conductivity, reaction activity, photocatalysis, and permeability, which may lead to greater toxicity to organisms. Given that TiO2 was classified as a category 2B carcinogen (possibly carcinogenic to humans), the genotoxicity of TiO2 NPs has become the focus of attention. There have been a series of previous studies investigating the potential genotoxicity of TiO2 NPs, but the existing research results are still controversial and difficult to conclude. More than half of studies have shown that TiO2 NPs can cause genotoxicity, suggesting that TiO2 NPs are likely to be genotoxic to humans. And the genotoxicity of TiO2 NPs is closely related to the exposure concentration, mode and time, and experimental cells/animals as well as its physicochemical properties (crystal type, size, and shape). This review summarized the latest research progress of related genotoxic effects through in vivo studies and in vitro cell tests, hoping to provide ideas for the evaluation of TiO2 NPs genotoxicity.