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Copper, a vital mineral nutrient, possesses redox qualities that make it both beneficial and toxic to organisms. Excessive environmental copper exposure can result in neurological damage and cognitive decline in humans. Astrocytes, the predominant glial cells in the brain, are particularly vulnerable to pollutants, but the mechanism of copper-induced damage to astrocytes remains elusive. The aim of this study was to determine the role of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in initiating NLRP3 inflammasome-induced astrocyte pyroptosis and chronic inflammation under conditions of copper overload. Our findings indicated that copper exposure elevated mitochondrial ROS (mtROS) levels, resulting in mitochondrial damage in astrocytes. This damage caused the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activated the cGAS-STING pathway. This activation resulted in interactions between STING and NLRP3 proteins, facilitating the assembly of the NLRP3 inflammasome and inducing pyroptosis. Furthermore, depletion of mtROS mitigated copper-induced mitochondrial damage in astrocytes and reduced mtDNA leakage. Pharmacological inhibition of STING or STING transfection further reversed copper-induced pyroptosis and the inflammatory response. In conclusion, this study demonstrated that the leakage of mtDNA into the cytoplasm and the subsequent activation of the cGAS-STING-NLRP3 pathway may be potential mechanisms underlying copper-induced pyroptosis in astrocytes. These findings provided new insights into the toxicity of copper.

Angiotensin II (Ang II) is an effective vasoconstriction peptide, a major effector molecule of the renin–angiotensin–aldosterone system (RAAS) and one of the important causes of endothelial dysfunction. Ferroptosis is considered to be involved in the occurrence and development of cardiovascular diseases. This study is dedicated to exploring the role and mechanism of Ang II-induced ferroptosis in HUVECs and to finding molecular targets for vascular endothelial injury and dysfunction during the progression of hypertension. In this study, we found that with the increase in exposure concentration, the intracellular ROS content and apoptosis rate increased significantly, the NO release decreased significantly in the medium- and high-concentration groups and the ET-1 content in the high-concentration group increased significantly. The expression of ZO-1 protein was significantly decreased in the high-concentration group. The expression of p-eNOS, VE-cadherin and Occludin protein showed a dose-dependent downward trend, while the ICAM-1 protein showed an upward trend. Ang II caused lipid metabolism disorders in HUVECs, and the PL–PUFAs associated with ferroptosis were significantly increased. In addition, Ang II promoted a significant increase in intracellular free Fe2+ content and MDA and a significant decrease in GSH content. Furthermore, the expression of GPX4, SLC7A11 and SLC3A2 was down-regulated, the expression of ACSL4, LPCAT3 and ALOX15 was up-regulated, and the ratio of p-cPLA2/cPLA2 was increased. After the intervention of ferroptosis inhibitor Fer-1, the injury and dysfunction of HUVECs induced by Ang II were significantly rescued. Immunofluorescence results showed that the expression of CD36 showed a significant increasing trend and was localized in the cytoplasm. Over-expression of CD36 promoted Ang II-induced ferroptosis and endothelial dysfunction. In conclusion, Ang II induces the injury of HUVECs, decreases vascular diastole and endothelial barrier-related molecules, and increases vascular constriction and adhesion-related molecules, which may be related to CD36 and its mediated lipid peroxidation and ferroptosis signals.

IntroductionIntracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. MethodsAdult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays.ResultsOur study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. DiscussionOur findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.

BackgroundNoise and dust are the most widespread occupational hazards. Animal studies have shown that they may cause impaired fasting glucose (IFG) by disturbing glucose metabolism and impairing the function of pancreatic islet cells, which can lead to further development of diabetes. ObjectiveTo investigate the effects of occupational noise or industrial dust exposure on the risk of impaired fasting plasma glucose (FPG) or diabetes mellitus in workers and potential combined effect of the two variables, and to provide a scientific basis for the prevention and control of diabetes mellitus in occupational groups. MethodsData on occupational health surveillance of a total of 6836 workers in noise exposure group, productive dust exposure group, and control group were collected and collated from the occupational health examination case data of an occupational health examination institution in Jiangsu Province in 2020. χ2 test, logistic regression analysis, and additive interaction model were used to analyze the relationships between occupational noise and/or productive dust exposure and IFG and diabetes.ResultsThe mean age of the 6836 workers was (44.1±9.6) years. Among them, 568 were assigned in the control group, 1961 in the noise-only exposure group, 1048 in the dust-only exposure group, and 3259 in the simultaneous exposure group. The prevalence of IFG in this study population was 9.61%, and the prevalence of diabetes was 7.36%. The results of logistic regression showed that the odds ratios (OR) of IFG and their 95% confidence intervals (CI) for IFG were 1.55 (1.01, 2.37), 1.67 (1.06, 2.64), and 2.60 (1.4, 3.89) in workers with noise exposure only, dust exposure only, and both exposures, respectively. The OR (95%CI) values for diabetes in workers exposed to noise only, dust only, and both were 1.76 (1.04, 3.00), 1.92 (1.12, 3.30), and 2.80 (1.71, 4.60), respectively. The results of interaction analysis showed no multiplicative interaction between noise and dust exposure on IFG (OR=0.94, 95%CI: 0.58, 1.51) or diabetes (OR=0.75, 95%CI: 0.42, 1.33). The relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) for noise and dust exposure on IFG were 0.30 (95%CI: −0.31, 0.92), 0.11% (95%CI: −0.13%, 0.35%), and 1.21 (95%CI: 0.74, 1.99), respectively. The three indicators for noise and dust exposure on diabetes were -0.02 (95%CI: −0.91, 0.87), 0.01% (95%CI: −0.29%, 0.28%), and 0.99 (95%CI: 0.66, 1.50), respectively, suggesting no additive interaction. ConclusionOccupational noise and industrial dust exposure are risk factors for IFG and diabetes mellitus, and a combined effect of concurrent exposure to these two factors is identified but not an interactive effect. Health monitoring and regular screening should be targeted at workers exposed to occupational noise and industrial dust to reduce the prevalence of IFG and diabetes mellitus in occupational population.

Abstract Background Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. Results Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. Conclusion The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity. Graphical abstract

ObjectiveTo explore the prevalence and early health effects of occupational stress among employees in a petrochemical enterprise for providing evidence to the implementation of relevant interventions in the employees. MethodsAn online self-administered questionnaire survey was carried out among 4 066 working employees of a petrochemical enterprise in Nanjing, Jiangsu province during September – October 2021. The Core Occupational Stress Scale (COSS)， Patient Health Questionnaire-9 (PHQ-9), Self-Rating Anxiety Scale (SAS)，the Five-Item World Health Organization Well-Being Index (WHO-5), Self-Administrated Sleep Questionnaire (SSQ)，and scales for fatigue accumulation and musculoskeletal disorders assessment were used in the survey. ResultsFor the 3 763 employees finally included in the analysis, 1 143 (30.4%) were assessed as having occupational stress. Among all the occupationally stressed employees, 607 (53.1%), 256 (22.4%), and 280 (24.5%) were judged as having mild, moderate, and severe occupational stress; the number (percentage) of the employees detected with abnormal conditions was 1 670 (44.4%) for depressive symptoms, 1 338 (35.6%) for anxiety symptoms, 2 016 (53.6%) for low life satisfaction, 1 548 (41.1%) for insomnia, 2 377 (63.2%) for fatigue accumulation, and 2 934 (78.0%) for musculoskeletal disorders, respectively. After adjusting for gender, age, education, marital status, average monthly income, job title, job type, working years of specific job type, weekly working hours, and work shift status，the results of unconditional multivariate logistic regression analysis showed that compared to those without occupational stress, the employees with occupational stress of different severity were at significantly increased risks of depressive symptoms (odds ratio [OR] = 3.582, 6.114 and 14.016 for the employees with mild, moderate or severe occupational stress), anxiety symptoms (OR = 4.268, 4.429 and 9.365), low life satisfaction (OR = 2.790, 2.896 and 7.849), insomnia symptoms (OR = 2.425, 3.033 and 5.218), fatigue accumulation (OR = 4.806,8.818 and 18.017), and musculoskeletal disorders (2.189, 2.381 and 4.367). ConclusionThe detection rate of occupational stress was relatively high and the stress exerted early adverse effects on health among employees of a petrochemical enterprise in Nanjing city .

Defective erythropoiesis is one of the causes of anemia and leukemia. However, the mechanisms underlying defective erythropoiesis under a low-dose environment of benzene are poorly understood. In the present study, multiple omics (transcriptomics and metabolomics) and methods from epidemiology to experimental biology (e.g., benzene-induced (WT and HIF-1α + ) mouse, hiPSC-derived HSPCs) were used. Here, we showed that erythropoiesis is more easily impacted than other blood cells, and the process is reversible, which involves HIF-1 and NF-kB signaling pathways in low-level benzene exposure workers. Decreased HIF-1α expression in benzene-induced mouse bone marrow resulted in DNA damage, senescence, and apoptosis in BMCs and HSCs, causing disturbances in iron homeostasis and erythropoiesis. We further revealed that HIF-1α mediates CCL3/macrophage-related immunosurveillance against benzene-induced senescent and damaged cells and contributes to iron homeostasis. Mechanistically, we showed that m6A modification is essential in this process. Benzene-induced depletion of m6A promotes the mRNA stability of gene NFKBIA and regulates the NF-κB/CCL3 pathway, which is regulated by HIF-1α/METTL3/YTHDF2. Overall, our results identified an unidentified role for HIF-1α, m6A, and the NF-kB signaling machinery in erythroid progenitor cells, suggesting that HIF-1α/METTL3/YTHDF2-m6A/NF-κB/CCL3 axis may be a potential prevention and therapeutic target for chronic exposure of humans to benzene-associated anemia and leukemia.

Colorectal cancer is the second leading cause of global cancer-related deaths, and its precursor lesions are colorectal polyps (CAP). The study aimed to explore the effect of combinations of unhealthy lifestyles on CAP and investigate the mediation role of metabolic disorder in this process. A total of 1299 adults were recruited from a hospital in Jiangsu, China, including 811 cases and 488 adults without diseases. The information on demographic characteristics and lifestyles was collected through questionnaires and the medical record system. Serum biochemical parameters were determined using the automatic biochemical analyzer. Adjusted regression analysis showed that unhealthy lifestyles, including smoking, overnight meals, daily water intake, staying up late, and exercise associated with the risk of CAP. Furthermore, metabolic biomarkers, including BMI, triglycerides, and uric acid, were associated with the risk of CAP. Also, unhealthy lifestyle scores were positively associated with BMI, triglycerides, and CAP. The mediation effect of metabolic biomarkers, such as BMI and triglycerides on the association of unhealthy lifestyle scores with CAP was significant. Available data demonstrate the adverse effect of combinations of unhealthy lifestyle factors on CAP, and metabolic disorders to potentially mediate the association of unhealthy lifestyles with the risk of CAP.

Abstract Porcine circovirus‐like virus P1, like porcine circovirus type 2 (PCV2), is a potential pathogen of post‐weaning multisystemic wasting syndrome in swine. Yaks are a valuable species and an iconic symbol of the Tibet Plateau which is the highest and largest plateau in the world. In this study, a total of 105 yak diarrheal samples, collected from 13 farms in Linzhi in the Tibet Plateau from January 2019 to December 2021, that were screened for P1 and PCV2 by polymerase chain reaction, 10.48% (n = 11) were positive for P1, 4.76% (n = 5) for PCV2, and 5.71% (n = 6) were positive for coinfection of P1 and PCV2. In addition, the whole genomes of eight P1 strains and eight PCV2 strains were sequenced. Alignment of deduced amino acid sequences of P1 ORF1 and PCV2 ORF2 gene revealed that ON012566 had one unique amino acid mutation at residues 137 (T to P). This mutation has important implication for the study of virus virulence, tissue tropism, and immune response. Phylogenetic analysis shows that the yak‐origin P1 strains in this study with cattle‐origin P1 reference strains were grouped into one cluster. The yak‐origin PCV2 (ON012566) and a buffalo‐origin PCV2 (KM116514) reference strain clustered in the same branch in the PCV2b regions. Meanwhile, the remaining PCV2 strains and buffalo‐origin PCV2 reference strain (ON012565) clustered in the PCV2d regions. To summarize, to our knowledge, this is the first report on the molecular prevalence and genome characteristics of P1 and PCV2 in yaks in the world and will contribute to further study of the molecular epidemiology, source, and evolution of P1 and PCV2 strains.

BackgroundN6-methyladenosine (m6A) RNA methylation may play an important role in the process of malignant transformation of cells induced by environmental carcinogens. However, the specific roles and mechanisms need to be further explored.ObjectiveTo explore the role and mechanism of m6A binding protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the malignant transformation of human gastric mucosal epithelial cells GES-1 induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).MethodsBased on the GES-1 malignant transformation cells MC-30, a stable knockdown IGF2BP3 MC-30 cell line (MC30-shIGF2BP3, abbreviated as MC30-shI3) was constructed by lentiviral transfection technology, and a negative control group (MC30-NC) was also prepared. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the mRNA expression and protein levels of IGF2BP3. RNA binding protein immunoprecipitation (RIP-qPCR) was used to examine the combination between IGF2BP3 protein and MYC mRNA in malignant cells MC-30. Furthermore, the stability of MYC mRNA was detected by actinomycin D assay. CCK-8 and Transwell respectively were employed to detect cell proliferation, migration, and invasion. Western blotting was applied to detect the expression of EMT markers (N-cadherin, Vimentin, α-SMA, and Snail). The role of the downstream target gene MYC was further elucidated by a rescue assay in MC30-shI3 cells transfected with a plasmid overexpressing MYC to observe changes in cellular phenotypes (proliferation, migration, invasion) and expression of key EMT proteins.ResultsCompared with the control group, the expression of IGF2BP3 mRNA was up-regulated after 5, 10, 20, and 40 μmol·L−1 MNNG infection of GES-1 cells (P

Bacterial infections continue to pose a significant global health challenge, with the emergence of multidrug-resistant (MDR) bacteria and biofilms further complicating treatment options. The rise of pan-resistant bacteria, coupled with the slow development of new antibiotics, highlights the urgent need for new therapeutic strategies. Nanotechnology-based biosensors offer fast, specific, sensitive, and selective methods for detecting and treating bacteria; hence, it is a promising approach for the diagnosis and treatment of MDR bacteria. Through mechanisms, such as destructive bacterial cell membranes, suppression of efflux pumps, and generation of reactive oxygen species, nanotechnology effectively combats bacterial resistance and biofilms. Nano-biosensors and related technology have demonstrated their importance in bacteria diagnosis and treatment, providing innovative ideas for MDR inhibition. This review focuses on multiple nanotechnology approaches in targeting MDR bacteria and eliminating antimicrobial biofilms, highlighting nano-biosensors via photodynamics-based biosensors, eletrochemistry biosensors, acoustic-dynamics sensors, and so on. Furthermore, the major challenges, opportunities of multi-physical-field biometrics-based biosensors, and relevant nanotechnology in MDR bacterial theranostics are also discussed. Overall, this review provides insights and scientific references to harness the comprehensive and diverse capabilities of nano-biosensors for precise bacteria theranostics and MDR inhibition.

Abstract Background Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. Methods The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. Results RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. Conclusions Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

BackgroundOccupational stress and depressive symptoms of disease prevention and control personnel are serious.ObjectiveTo investigate the relationship between occupational stress, psychological capital, and depressive symptoms of disease prevention and control personnel, and analyze the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms.MethodsFrom July to September 2020, a cluster random sampling method was used to select 2201 employees from 21 centers for disease control and prevention as study subjects covering all levels of administrative divisions in Jiangsu Province. A total of 2036 valid questionnaires were collected with a recovery rate of 92.5%. The Core Occupational Stress Scale, Patient Health Questionnaire, and Psychological Capital Questionnaire were used to investigate their occupational stress, depressive symptoms, and psychological capital. Stratified regression analysis was used to explore the effects of occupational stress and psychological capital on depressive symptoms. A mediating effect model was used to analyze and verify the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms.ResultsThe total scores in M (P25, P75) of occupational stress, depressive symptoms, and psychological capital in the target population were 42.0 (37.0, 48.0), 8.0 (4.0, 9.0), and 4.6 (4.0, 5.0) respectively. The positive rate of occupational stress was 31.0% (631/2036), and the positive rate of depressive symptoms was 22.0% (448/2036). The dimensional scores of organization and reward, and demand and effort of occupational stress were positively correlated with the total score of depressive symptoms [Spearman correlation coefficients (rs) were 0.371 and 0.269, P

Microplastics and Nanoplastics (MNPLs) pollution has been recognized as the important environmental pollution caused by human activities in addition to global warming, ozone layer depletion and ocean acidification. Most of the current studies have focused on the toxic effects caused by plastics and have not actively investigated the mechanisms causing cell death, especially at the subcellular level. The main content of this paper focuses on two aspects, one is a review of the current status of MNPLs contamination and recent advances in toxicological studies, which highlights the possible concentration levels of MNPLs in the environment and the internal exposure of humans. It is also proposed to pay attention to the compound toxicity of MNPLs as carriers of other environmental pollutants and pathogenic factors. Secondly, subcellular toxicity is discussed and the modes of entry and intracellular distribution of smaller-size MNPLs are analyzed, with particular emphasis on the importance of organelle damage to elucidate the mechanism of toxicity. Importantly, MNPLs are a new type of environmental pollutant and researchers need to focus not only on their toxicity, but also work with governments to develop measures to reduce plastic emissions, optimize degradation and control plastic aggression against organisms, especially humans, from multiple perspectives.

The presence of anti-GQ1b antibodies in serum or cerebrospinal fluid is a diagnostic indicator of the Miller–Fisher variant of Guillain–Barré syndrome (GBS), whereas anti-GQ1b antibody syndrome is rarely presented as acute bilateral pain in the cheeks and masticatory muscle fatigue without ophthalmoplegia, ataxia, or limb weakness. Here, we report a case of a female patient diagnosed with GBS characterized only by the involvement of the facial and trigeminal nerves who was positive for serum anti-GQ1b antibodies secondary to Mycoplasma pneumoniae infection. The patient was treated with macrolide antibiotics and neurotrophic drugs, and her symptoms were significantly alleviated after 1 month. This case indicates a new clinical presentation of GBS and anti-GQ1b antibody syndrome with a differential diagnosis of multiple cranial nerve damage of which neurological physicians should be aware. Positive anti-GQ1b antibodies secondary to infection were observed in this case, and antibiotic treatment resulted in a favorable prognosis. The specific underlying mechanism requires further investigation.

Benzene is a common industrial chemical and environmental pollutant. However, the mechanism of hematotoxicity caused by exposure to low doses of benzene is unknown. Let-7e-5p pathway regulatory networks were constructed by bioinformatics analysis using a benzene-induced aplastic anemia (BIAA) mouse model. The MTT assay, EdU staining, flow cytometric analysis, dual luciferase reporter gene assay, and RIP assay were utilized to evaluate the effects of benzoquinone (1,4-BQ) on let-7e-5p pathway. This study consisted of 159 workers with a history of low-level benzene exposure and 159 workers with no history of benzene exposure. After the confounding factors were identified, the associations between let-7e-5p expression and hematotoxicity were assessed by multiple linear regression. Furthermore, we used four machine learning algorithms (decision trees, neural network, Bayesian network, and support vector machines) to construct a predictive model for detecting benzene-causing hematotoxicity in workers. In this study, compared with respective controls, let-7e-5p expression was decreased in BIAA mice and benzene-exposed workers. After 1,4-BQ exposure, let-7e-5p overexpression negatively regulated caspase-3 and p21 expression, protected cells from apoptosis, and facilitated cell proliferation. RIP assays, and dual luciferase reporter gene assays confirmed that let-7e-5p could target p21 and caspase-3 and regulate the cell cycle and apoptosis. The support vector machines classifier achieved the best prediction of benzene-induced hematotoxicity (prediction accuracy = 88.27, AUC = 0.83) by statistically characterizing the internal dose of benzene exposure and the oxidative stress index, as well as the expression levels of let-7e-5p pathway-related genes in benzene-exposed workers. Let-7e-5p may be a potential therapeutic target of benzene-induced hematotoxicity, provide a basis for evaluating the health hazards of long-term and low-dose benzene exposure in workers, and supply a reference for revising occupational health standards.

Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD+ in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.

Abstract Background In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of the middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM2.5 (fine particulate matter) and O3 (ozone) on non-accidental mortality and respiratory mortality of the middle-aged and elderly people in Lishui District of Nanjing and provide the evidence for potential prevention and control measures of air pollution. Method Using daily mortality and atmospheric monitoring data from 2015 to 2019, we applied a generalized additive model with time-series analysis to evaluate the association of PM2.5 and O3 exposure with daily non-accidental mortality and respiratory mortality in Lishui District. Using the population attributable fractions to estimate the death burden caused by short-term exposure to O3 and PM2.5。. Result For every 10 μg/m3 increase in PM2.5, non-accidental mortality increased 0.94% with 95% confidence interval (CI) between 0.05 and 1.83%, and PM2.5 had a more profound impact on females than males. For every 10 μg/m3 increase in O3, respiratory mortality increased 1.35% (95% CI: 0.05, 2.66%) and O3 had a more profound impact on males than females. Compared with the single pollutant model, impact of the two-pollutant model on non-accidental mortality and respiratory mortality slightly decreased. In summer and winter as opposed to the other seasons, O3 had a more obvious impact on non-accidental mortality. The population attributable fractions of non-accidental mortality were 0.84% (95% CI:0.00, 1.63%) for PM2.5 and respiratory mortality were 0.14% (95% CI:0.01, 0.26%) for O3. For every 10 μg/m3 decrease in PM2.5, 122 (95% CI: 6, 237) non-accidental deaths could be avoided. For every 10 μg/m3 decrease in O3, 10 (95% CI: 1, 38) respiratory deaths could be avoided. Conclusion PM2.5 and O3 could significantly increase the risk of non-accidental and respiratory mortality in the middle-aged and elderly people in Lishui District of Nanjing. Exposed to air pollutants, men were more susceptible to O3 damage, and women were more susceptible to PM2.5 damage. Reduction of PM2.5 and O3 concentration in the air may have the potential to avoid considerable loss of lives.

Health risks caused by crucial environmental carcinogens N-nitrosamines triggered ubiquitous attention. As the liver exerted vital function through metabolic process, lipid metabolism disorders have been confirmed as potential drivers for toxicological effects, and the mechanisms of lipid regulation related to hepatotoxicity induced by N-nitrosamines remained largely unclear. In this study, we comprehensively explored the disturbance of hepatic lipid homeostasis in mice induced by nitrosamines. The results implied that nitrosamines exposure induced hepatotoxicity accompanied by liver injury, inflammatory infiltration, and hepatic edema. Lipidomics profiling analysis indicated the decreased levels of phosphatidic acids (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), lyso-phosphatidylcholines (LPC), lyso-phosphatidylethanolamines (LPE), diacylglycerols (DAG) and triacylglycerols (TAG), the elevation of ceramides (Cer) and decomposition of free fatty acids (FFA) in high-dose nitrosamines exposure group. Importantly, nitrosamines exposure promoted fatty acid oxidation (FAO) by facilitating fatty acid uptake and decomposition, together with the upregulation of genes associated with FAO accompanied by the activation of inflammatory cytokines TNF-α, IL-1β and NLRP3. Furthermore, fatty acid translocase CD36-mediated fatty acid oxidation was correlated with the enhancement of oxidative stress in the liver caused by nitrosamines exposure. Overall, our results contributed to the new strategies to interpret the early toxic effects of nitrosamines exposure.

ObjectiveThis study aims to systematically evaluate the curative efficacy of different acupuncture methods in the treatment of obesity combined with insulin resistance in randomized clinical trials (RCTs) by network meta-analysis.MethodsFour Chinese databases (CNKI, WanFang Data, VIP, and SinoMed) and four English databases (PubMed, Embase, the Cochrane Library, and www.clinicaltrial.gov) were electronically searched to identify qualified studies. Two reviewers independently screened the literature in accordance with the inclusion/exclusion criteria by EndNote 20 software and extracted data by ADDIS1.16.8 software, and then the risk of bias of the included studies were evaluated by the Cochrane tool. Network meta-analysis was performed by Stata 15.1 software. The primary outcomes included fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment—insulin resistance (HOMA-IR), and body mass index (BMI). The secondary outcomes included waistline, waist–hip ratio, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL).ResultsFive RCTs with a total of 410 patients with obesity combined with insulin resistance were included. The results of the network meta-analysis showed that, compared with the control group, three kinds of acupuncture methods (electropuncture, acupoint catgut embedding, and acupuncture point patch) had significant efficacy in reducing FBG [electropuncture (MD = -0.44, 95% CI: -0.83, -0.05) and acupoint catgut embedding (MD = -0.36, 95% CI: -0.51, -0.21)], FINS [electropuncture (MD = -6.17, 95% CI: -9.69, -2.65), acupoint catgut embedding (MD = -5.87, 95% CI: -6.92, -4.82), and acupuncture point patch (MD = -5.86, 95% CI: -11.40, -0.32)], HOMA-IR [electropuncture (MD = -1.59, 95% CI: -2.73, -0.45) and acupoint catgut embedding (MD =-0.91, 95% CI: -1.07, -0.75)], BMI [electropuncture (MD = -1.68, 95% CI: -2.70, -0.66), acupoint catgut embedding (MD = -3.39, 95% CI: -4.38, -2.40), and acupuncture point patch [MD = -2.90, 95%CI: -4.93, -0.87)], and waistline [electropuncture (MD = -5.49, 95% CI: -8.56, -2.42) and acupoint catgut embedding (MD = -4.91, 95% CI: -7.51, -2.31)] in obese patients with insulin resistance, suggesting that their efficacy was better than that of the western medicine group in some of the outcome indicators. For the index related to blood lipid, the efficacy of electropuncture was significantly better than behavioral therapy and western medicine. Except that acupoint catgut embedding was superior to electroacupuncture in reducing the BMI, there was no statistically significant difference in efficacy among the three acupuncture methods.ConclusionsThe results showed that the therapeutic effect of acupuncture methods was superior to conventional western treatment alone. Acupuncture methods could serve as an alternative or adjunctive treatment in obese patients with insulin resistance.Systematic Review Registrationhttps://inplasy.com, identifier 202280075.

Lung cancer-specific clinical specimens, such as alveolar lavage fluid, are typically identified by microscopic biopsy, which has limited specificity and sensitivity and is highly susceptible to human manipulation. In this work, we present an ultrafast, specific, and accurate cancer cell imaging strategy based on dynamically self-assembling fluorescent nanoclusters. The presented imaging strategy can be used as an alternative or a complement to microscopic biopsy. First, we applied this strategy to detect lung cancer cells, and established an imaging method that can rapidly, specifically, and accurately distinguish lung cancer cells (e.g., A549, HepG2, MCF-7, Hela) from normal cells (e.g., Beas-2B, L02) in 1 min. In addition, we demonstrated that the dynamic self-assembly process that fluorescent nanoclusters formed by HAuCl4 and DNA are first generated at the cell membrane and then gradually enter the cytoplasm of lung cancer cells in 10 min. In addition, we validated that our method enables the rapid and accurate imaging of cancer cells in alveolar lavage fluid samples from lung cancer patients, whereas no signal was observed in the normal human samples. These results indicate that the dynamic self-assembling fluorescent nanoclusters-based cancer cells imaging strategy could be an effective non-invasive technique for ultrafast and accurate cancer bioimaging during liquid biopsy, thus providing a safe and promising cancer diagnostic platform for cancer therapy.

Nanoplastics, including polystyrene nanoplastics (PS-NPs), are widely existed in the atmosphere, which can be directly and continuously inhaled into the human body, posing a serious threat to the respiratory system. Therefore, it is urgent to estimate the potential pulmonary toxicity of airborne NPs and understand its underlying mechanism. In this research, we used two types of human lung epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) and (human pulmonary alveolar epithelial cells, HPAEpiC) to investigate the association between lung injury and PS-NPs. We found PS-NPs could significantly reduce cell viability in a dose-dependent manner and selected 7.5, 15 and 30 μg/cm2 PS-NPs as the exposure dosage levels. Microarray detection revealed that 770 genes in the 7.5 μg/cm2 group and 1951 genes in the 30 μg/cm2 group were distinctly altered compared to the control group. Function analysis suggested that redox imbalance might play central roles in PS-NPs induced lung injury. Further experiments verified that PS-NPs could break redox equilibrium, induce inflammatory effects, and triggered apoptotic pathways to cause cell death. Importantly, we found that PS-NPs could decrease transepithelial electrical resistance by depleting tight junctional proteins. Result also demonstrated that PS-NPs-treated cells increased matrix metallopeptidase 9 and Surfactant protein A levels, suggesting the exposure of PS-NPs might reduce the repair ability of the lung and cause tissue damage. In conclusion, nanoplastics could induce oxidative stress and inflammatory responses, followed by cell death and epithelial barrier destruction, which might result in tissue damage and lung disease after prolonged exposure.

Tri-n-butyl phosphate (TnBP), a typical alkyl organophosphate ester is widely used as an emerging flame retardant for polybrominated diphenyl ethers alternatives, but the potential toxicity and mechanism are unclear. In this study, the reproductive toxicity of TnBP and its related mechanisms were explored using the Caenorhabditis elegans (C. elegans) model. After TnBP (100–1000 μg/L) exposure, brood size and the number of fertilized eggs in the uterus in C. elegans were significantly reduced, the relative area of gonad arm and the number of total germline cells in C. elegans were significantly reduced, germ cell apoptosis and germ cell DNA damage in C. elegans were significantly increased, the level of ROS in C. elegans was significantly increased. Furthermore, TnBP exposure caused abnormal gene expressions of cell apoptosis (ced-9, ced-4 and ced-3), DNA damage (hus-1, clk-2, cep-1 and egl-1) and oxidative stress (mev-1 and gas-1). TnBP exposure can lead to reproductive ability decreased and gonad development impaired in C. elegans, the mechanism of TnBP reduced reproductive ability may be related to germ cell apoptosis, germ cell DNA damage and oxidative stress. Environmental exposure to TnBP may have potential reproductive toxicity.

Lithium-rich antiperovskites (LiRAPs) hold great promise to be the choice of solid-state electrolytes (SSEs) owing to their high ionic conductivity, low activation energy, and low cost. However, processing sheet-type solid-state Li metal batteries (SSLiB) with LiRAPs remains challenging due to the lack of robust techniques for battery processing. Herein, we propose a scalable slurry-based procedure to prepare a flexible composite electrolyte (CPE), in which LiRAP (e.g., Li2OHCl0.5Br0.5, LOCB) and nitrile butadiene rubber (NBR) serve as an active filler and as a polymer scaffold, respectively. The low-polar solvent helps to stabilize the LiRAP phase during slurry processing. It is found that the addition of LOCB into the NBR polymer enhances the Li ion conductivity for 2.3 times at 60°C and reduces the activation energy (max. 0.07 eV). The as-prepared LOCB/NBR CPE film exhibits an improved critical current of 0.4 mA cm−2 and can stably cycle for over 1000 h at 0.04 mA cm−2 under 60°C. In the SSLiB with the sheet-type configuration of LiFePO4(LFP)||LOCB/NBR CPE||Li, LFP exhibits a capacity of 137 mAh/g under 60 at 0.1°C. This work delivers an effective strategy for fabrication of LiRAP-based CPE film, advancing the LiRAP-family SSEs toward practical applications.

Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and H2O2. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.

(1) Background: Increasing evidence reveals that airborne plastic particles will continue to degrade into nanoplastics which are then inhaled by humans, causing injury to the respiratory system with controversial molecular mechanisms. (2) Methods: We used polystyrene nanoplastics (PS-NPs) as the representative pollutants to explore the inhalation toxicology of nanoplastics and identified the potential mechanism through high-throughput sequencing. (3) Results: PS-NPs inhibited cell viability in a dose-dependent manner and 0 μg/cm2, 7.5 μg/cm2 and 30 μg/cm2 PS-NP-treated groups were selected for RNA-seq. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that lung injuries caused by PS-NPs were mediated via redox imbalance, which was verified by reactive oxygen species (ROS) staining. Additionally, we obtained ten key transcription factors (TFs) governing differentially expressed genes (DEGs), nine of which were involved in the regulation of oxidative stress. An oxidative stress-associated TF-mRNA regulatory network was constructed on account of the findings above. Further joint analysis with animal experiment data from the GEO database identified a crucial oxidative stress-related molecule, TNFRSF12A. qRT-PCR was performed to confirm the results of RNA-seq. (4) Conclusions: Our study indicates the potential role of oxidative stress in the mechanism of nanoplastics-induced lung injuries, with several key genes being promising targets to analyze in future investigations.

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.

Benzene is a ubiquitous, occupational, and environmental hematotoxic and leukemogen. Damage to hematopoietic stem cells (HSCs) induced by benzene and its metabolites is a key event in bone marrow (BM) depression and leukemogenesis. There are no reports on transcriptome profiles of HSCs following benzene exposure. Here, Smart-seq2 single-cell transcriptome sequencing was used to detect transcriptomic alternations in BM HSCs and peripheral blood HSCs (PBSCs) in male C57B/6 mice exposed to benzene. We found that benzene caused hematotoxicity which was confirmed by routine blood test, pathological examination, and HSCs percentage analysis. A total of 1514 differentially expressed genes (DEGs) in BM HSCs and 1703 DEGs in PBSCs were screened after treatment with benzene. Weighted gene correlation network analysis revealed that pathways in cancer, transcriptional misregulation in cancer, and hematopoietic cell lineage are vital pathways involved in benzene-induced toxicity in BM HSCs, whereas hematopoietic cell lineage and leukocyte transendothelial migration are critical pathways in PBSCs. Of note, there were 164 common DEGs in both HSCs, out of which 53 genes were co-regulated in both types of HSCs. Subsequent pathway analysis of these 53 genes indicated that the most relevant pathways involved neutrophil degranulation and CD93 localized in the core of the network of the 53 genes, which are known to regulate leukemia stem cell self-renewal and quiescence. Our results could enhance our understanding of HSC responses to benzene, facilitate the identification of potential molecular biomarkers and future studies on its mechanism of toxicity toward HSCs.

Carbon dots (CDs) are a new class of carbon-based luminescence materials with fascinating properties. They have been given great expectations on superseding traditional semiconductor quantum dots due to their good dispersity and stability, relatively low toxicity, superior resistance to photobleaching, and excellent biocompatibility. The diversified luminescence properties of CDs are largely due to the synthetic strategies and precursors. In view of those described above, this study has explored the possibility to establish a facile one-step hydrothermal method for the one-pot synthesis of folic acid-modified cerium-doped CDs (Ce-CDs-FA), which could be further utilized as a sensitive fluorescent nanoprobe for biosensing. This investigation demonstrates that the Ce-CDs-FA nanocomposites have nice biocompatibility and bright fluorescent properties, which can be readily utilized to detect cancer cells through recognizing overexpressing folate receptors by virtue of folic acid. Meanwhile, it is noted that the Fe3+ ion can actualize a specific and hypersensitive quenching effect for these Ce-CDs-FA nanocomposites, which can be further explored for special ion recognition, including iron ions. It raises the possibility that the as-prepared Ce-CDs-FA nanocomposites could be extended as a dual fluorescence sensor for targeted cell imaging and Fe3+ ion detection.

Porcine circovirus-like virus P1 can infect many kinds of animals and mainly causes postweaning multisystemic wasting syndrome. In China, the genetic diversity, variation, and evolutionary processes of this virus have not been described yet. To improve our knowledge of its genetic diversity, evolution, and gene flow, we performed a bioinformatics analysis using the available nucleotide sequences of the P1 virus; among them, 12 nucleotide sequences were from ten pig farms in Jiangsu Province in this epidemiological survey, and 84 sequences were downloaded from GenBank. The P1 sequences showed a rich composition of AT nucleotides. Analyses of the complete genomic sequences were polymorphic and revealed high haplotype (gene) diversity and nucleotide diversity. A phylogenetic analysis based on the NJ method showed that all P1 virus sequences formed two distinct groups: A and B. High genetic differentiation was observed between strains from groups A and B. The codon usage pattern of P1 was affected by dinucleotide compositions. Dinucleotide UU/CC was overrepresented, and dinucleotide CG was underrepresented. The mean evolutionary rate of the P1 virus was estimated to be 3.64 × 10−4 nucleotide substitutions per site per year (subs/site/year). The neutrality tests showed negative values. The purifying selection and recombination events may play a major driving role in generating the genetic diversity of the P1 population. The information from this research may be helpful to obtain new insights into the evolution of P1.

Abstract Background miRNA clusters are widely expressed across species, accumulating evidence has illustrated that miRNA cluster functioned more efficiently than single miRNA in cancer oncogenesis. It is likely that miRNA clusters are more stable and reliable than individual miRNA to be biomarkers for diagnosis and therapy. We previously found low expression of miR-144/451 was closely related with the risk for esophageal cancer. Researches on miR-144/451 cluster were mostly focused on individual miRNA but not the whole cluster, the regulatory mechanism of miRNA cluster were largely unknown. Methods In present study, we firstly analysed biological functions of individual miRNAs of miR-144/451 in ECa9706 transfected with miRNA mimics. We further analysed the biological function of the whole cluster in stable transgenic cell overexpressing miR-144/451. We then performed genome-wide mRNA microarray to detect differentially expressed gene profiles in stable transgenic cells. Results Overexpression of miR-144-3p promoted early apoptosis of ECa9706 and inhibited cell migration, cell invasion and cell proliferation. miR-144-5p and miR-451a inhibited cell proliferation, at the same time, miR-451a inhibited cell migration. Overexpression of miR-144/451 leads to the arrest cell cycle from S to G2 and G2 to M,while the invasion ability was obviously inhibited. We further observed c-Myc, p-ERK were downregulated in cells overexpressing miR-144/451, while p53 was up-regulated. The downstream effectors of c-Myc, MMP9 and p-cdc2 were downregulated in miR-144/451 stable transgenic cell. miR-144/451 may or partly inhibited cell cycles and invasion of ECa9706 through inhibiting ERK/c-Myc signaling pathway. Conclusion Collectively, we analysed the function of miR-144/451 cluster from individual to overall level. miR-144/451 cluster played proto oncogene role in esophageal cancer by inhibiting cell invasion.

Abstract Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for Hepatocellular carcinoma (HCC) patients. This study aims to capture the current research hotspots of HCC, based on the analysis of publications related to HCC research from 2013 to 2017, and to identify a novel lncRNA signature for HCC prognosis through the data mining in The Cancer Genome Atlas (TCGA). “Prognosis” and “biomarker” were located in the core of the HCC research hotspot. Moreover, long noncoding RNA was the top one research frontier in HCC research. The associations between survival outcome and the expression of lncRNAs were evaluated by the univariate and multivariate Cox proportional hazards regression analyses. Four lncRNAs (LINC00261, TRELM3P, GBP1P1, and CDKN2B‐AS1) were identified as significantly correlated with overall survival (OS). These four lncRNAs were gathered as a single prognostic signature. There was a significant positive correlation between HCC patients with low‐risk scores and overall survival (HR = 1.802, 95%CI [1.224‐2.652], P = .003). Further analysis suggested that the prognostic value of this four‐lncRNA signature was independent in clinical features. The enrichment analysis of prognostic lncRNA‐related gene was performed to find out the related pathways. Our study indicates that this novel lncRNA expression signature may be a useful biomarker of the prognosis for HCC patients, based on bioinformatics analysis.

Currently, studies worldwide have comprehensively recognized the importance of Sphingomonadaceae bacteria and the mlrCABD gene cluster in microcystin (MC) degradation. However, knowledge about their degradation of nodularin (NOD) is still unclear. In this study, the degradation mechanism of NOD by Sphingopyxis sp. m6, an efficient MC degrader isolated from Lake Taihu, was investigated in several aspects, including degradation ability, degradation products, and potential application. The strain degraded NOD of 0.50 mg/L with a zero-order rate constant of 0.1656 mg/L/d and a half-life of 36 h. The average degradation rate of NOD was significantly influenced by the temperature, pH, and initial toxin concentrations. Moreover, four different biodegradation products, linear NOD, tetrapeptide H-Glu-Mdhb-MeAsp-Arg-OH, tripeptide H-Mdhb-MeAsp-Arg-OH, and dipeptide H-MeAsp-Arg-OH, were identified, of which the latter two are the first reported. Furthermore, the four mlr genes were upregulated during NOD degradation. The microcystinase MlrA encoded by the mlrA gene hydrolyzes the Arg-Adda bond to generate linear NOD as the first step of NOD biodegradation. Notably, recombinant MlrA showed higher degradation activity and stronger environmental adaptability than the wild strain, suggesting future applications in NOD pollution remediation. This research proposes a relatively complete NOD microbial degradation pathway, which lays a foundation for exploring the mechanisms of NOD degradation by MC-degrading bacteria.

Background Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and

Microcystins (MCs), which are produced by harmful cyanobacteria blooms, pose a serious threat to environmental health. However, the effect of MCs on the bacterial community under anaerobic conditions is still unclear. This study examined the dynamic changes of MC-degrading capacity, metabolic activity, and structure of the bacterial community in lake sediment repeatedly treated with 1 mg/L microcystin-LR (MC-LR) under anaerobic conditions. The results showed that the MC-degrading capacity of the bacterial community was increased nearly three-fold with increased treatment frequency. However, the metabolic profile behaved in exactly opposite trend, in which the overall carbon metabolic activity was inhibited by repeated toxin addition. Microbial diversity was suppressed by the first addition of MC-LR and then gradually recovered. The 16S amplicon sequencing showed that the dominant genera were changed from Exiguobacterium and Acinetobacter to Prosthecobacter, Dechloromonas, and Agrobacterium. Furthermore, the increase in the relative abundance of Dechloromonas, Pseudomonas, Hydrogenophaga, and Agrobacterium was positively correlated with the MC-LR treatment times. This indicates that they might be responsible for MC degradation under anaerobic conditions. Our findings reveal the relationship between MC-LR and the sediment bacterial community under anaerobic conditions and indicate that anaerobic biodegradation is an effective and promising method to remediate MCs pollution.

Objectives To comprehensively analyse the global scientific outputs of hepatocellular carcinoma (HCC) research. Methods Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace IV and Excel 2016 to analyse literature information, including journals, countries/regions, institutes, authors, citation reports and research frontiers. Results Until March 31, 2018, a total of 24,331 papers in HCC research were identified as published between 2008 and 2017. Oncotarget published the most papers. China contributed the most publications and the United States occupied leading positions in H-index value and the number of ESI top papers. Llovet JM owned the highest co-citations. The keyword “transarterial chemoembolization” ranked first in the research front-line. Conclusions The amount of papers published in HCC research has kept increasing since 2008. China showed vast progress in HCC research, but the United States was still the dominant country. Transarterial chemoembolization, epithelial-mesenchymal transition, and cancer stem cell were the latest research frontiers and should be paid more attention.

Microcystin-LR (MC-LR) is the most widely distributed microcystin (MC) that is hazardous to environmental safety and public health, due to high toxicity. Microbial degradation is regarded as an effective and environment-friendly method to remove it, however, the performance of MC-degrading bacteria in environmentally relevant pollution concentrations of MC-LR and the degradation pathways remain unclear. In this study, one autochthonous bacterium, Sphingopyxis sp. m6 which exhibited high MC-LR degradation ability, was isolated from Lake Taihu, and the degrading characteristics in environmentally relevant pollution concentrations were demonstrated. In addition, degradation products were identified by utilizing the full scan mode of UPLC-MS/MS. The data illustrated that strain m6 could decompose MC-LR (1⁻50 μg/L) completely within 4 h. The degradation rates were significantly affected by temperatures, pH and MC-LR concentrations. Moreover, except for the typical degradation products of MC-LR (linearized MC-LR, tetrapeptide, and Adda), there were 8 different products identified, namely, three tripeptides (Adda-Glu-Mdha, Glu-Mdha-Ala, and Leu-MeAsp-Arg), three dipeptides (Glu-Mdha, Mdha-Ala, and MeAsp-Arg) and two amino acids (Leu, and Arg). To our knowledge, this is the first report of Mdha-Ala, MeAsp-Arg, and Leu as MC-LR metabolites. This study expanded microbial degradation pathways of MC-LR, which lays a foundation for exploring degradation mechanisms and eliminating the pollution of microcystins (MCs).

This study was conducted to obtain the basic data of two common odorants—geosmin and 2-methylisoborneol (GSM and 2-MIB)—in environmental water. More specifically, the headspace solid-phase microextraction coupled to gas chromatography mass spectrometry (HS-SPME/GC-MS) was applied to determine the levels of GSM and 2-MIB in water samples, and the samples were collected depending on water sources, conventional treatment processes, and seasons. The significant difference was shown for the 2-MIB levels of source water P

Microcystin-LR (MC-LR) and microcystin-RR (MC-RR) produced by harmful cyanobacterial blooms (HCBs) pose substantial threats to the ecosystem and public health due to their potential hepatotoxicity. Degradation of microcystins (MCs) by indigenous bacteria represents a promising method for removing MCs from fresh water without harming the aquatic environment, but only a few microcystin (MC)-degrading bacteria have been isolated and had their mechanisms reported. This study aimed to isolate indigenous bacteria from Lake Taihu, and investigate the capability and mechanism of MC degradation by these bacteria. During a Microcystis bloom, an indigenous MC-degrading bacterium designated MC-LTH2 was successfully isolated from Lake Taihu, and identified as Stenotrophomonas acidaminiphila based on phylogenetic analysis. In the presence of MC-LR together with MC-RR, the strain MC-LTH2 was capable of totally degrading both simultaneously in 8 days, at rates of 3.0 mg/(L⋅d) and 5.6 mg/(L⋅d), respectively. The degradation rates of MCs were dependent on temperature, pH, and initial MC concentration. Adda (3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid) was detected as an intermediate degradation product of MCs using high performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). To the best of our knowledge, this is the first report of Stenotrophomonas acidaminiphila capable of degrading two MC analogues and other compounds containing Adda residue completely under various conditions, although the mlrA gene in the strain was not detected. These results indicate the Stenotrophomonas acidaminiphila strain MC-LTH2 possesses a significant potential to be used in bioremediation of water bodies contaminated by MC-LR and MC-RR, and is potentially involved in the degradation of MCs during the disappearance of the HCBs in Lake Taihu.

The pressing issue of earthy and musty odor compounds in natural waters, which can affect the organoleptic properties of drinking water, makes it a public health concern. A simple and sensitive method for simultaneous analysis of five odorants in environmental water was developed by headspace solid-phase microextraction (HS-SPME) coupled to chromatography-mass spectrometry (GC-MS), including geosmin (GSM) and 2-methylisoborneol (2-MIB), as well as dimethyl trisulfide (DMTS), β-cyclocitral, and β-ionone. Based on the simple modification of original magnetic stirrer purchased from CORNING (USA), the five target compounds can be separated within 23 min, and the calibration curves show good linearity with a correlation coefficient above 0.999 (levels = 5). The limits of detection (LOD) are all below 1.3 ng L−1, and the relative standard deviation (%RSD) is between 4.4% and 9.9% (n = 7) and recoveries of the analytes from water samples are between 86.2% and 112.3%. In addition, the storage time experiment indicated that the concentrations did not change significantly for GSM and 2-MIB if they were stored in canonical environment. In conclusion, the method in this study could be applied for monitoring these five odorants in natural waters.

Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

A technique was developed for simultaneous detection of fenitrothion (FNT) and chlorpyrifos-methyl (CLT) using a photonic suspension array based on silica colloidal crystal beads (SCCBs). The SCCBs were encoded with the characteristic reflection peak originating from the stop-band of colloidal crystal. This approach avoids the bleaching, fading or potential interference seen when encoding by fluorescence. SCCBs with a nanopatterned surface had increased biomolecule binding capacity and improved stability. Under optimal conditions, the proposed suspension array allowed simultaneous detection of the selected pesticides in the ranges of 0.25 to 1024 ng/mL and 0.40 to 735.37 ng/mL, with the limits of detection (LODs) of 0.25 and 0.40 ng/mL, respectively. The suspension array was specific and had no significant cross-reactivity with other chemicals. The mean recoveries in tests in which samples were spiked with target standards were 82.35% to 109.90% with a standard deviation within 9.93% for CLT and 81.64% to 108.10% with a standard deviation within 8.82% for FNT. The proposed method shows a potentially powerful capability for fast quantitative analysis of pesticide residues.

MicroRNAs (miRNAs), 18-24 nt non-coding RNAs, are thought to play important roles in cell proliferation, differentiation, apoptosis, and development. Recent studies suggest that some of the known microRNAs map to a single genomic locale within a single polycistronic transcript. But the roles of the cluster remain to be known. In order to understand the role and mechanism of a cluster of miR-143 and miR-145 in esophageal squamous cell carcinoma (ESCC), the association of mature miR-143 and miR-145 expression with the risk for esophageal cancer was evaluated in ESCC patients with a case-control study, and target protein regulated by mature miRNA was analyzed in ESCC cell lines with 3'UTR luciferase reporter assay. The expression levels of miR-143 and miR-145 were determined in 110 pairs of esophageal cancer tissues and adjacent normal tissues using real-time reverse transcription PCR. The relative expression of miR-143 and miR-145 were statistically different between cancer tissues and matched controls. The combined expression of miR-143 and miR-145 was significantly associated with the risk for esophageal cancer. Meanwhile, the reduced expression of two miRNAs in tumor patient was supposed to have a trend of lymph node metastases. The co-expression pattern of miR-143 and miR-145 was analyzed with Pearson correlation. It showed a significant correlation between these two miRNAs expression both in tissues and tumor cell lines. 3'UTR luciferase reporter assay indicated that Fascin Homolog 1 (FSCN1) could be co-regulated by miR-143 and miR-145. The protein level of FSCN1 showed no significant linear correlation with miR-143 and miR-145 expression in ESCC cell lines with Western blotting analysis. In conclusion, since miR-143 and miR-145 could regulate oncogenic FSCN1 and take part in the modulation of metastases, the result suggested the combination variable of miR-143 and miR-145 as a potential biomarker for earlier diagnosis and prognosis of esophageal cancer.

Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. However, it is still unclear which factors are involved in this downregulation. TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. Androgen stimulation can increase expression of the TMPRSS2-ERG fusion in fusion positive prostate cancer cells. The purpose of this investigation is to determine whether PSMA expression can be regulated by the TMPRSS2-ERG gene fusion. We employed two PSMA positive cell lines: VCaP cells, which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. After 24 hours of androgen treatment, TMPRSS2-ERG mRNA level was increased in VCaP cells. PSMA mRNA level was dramatically decreased in VCaP cells, while it only has moderate change in LNCaP cells. Treatment with the androgen antagonist flutamide partially restored PSMA expression in androgen-treated VCaP cells. Knocking down ERG by siRNA in VCaP cells enhances PSMA expression both in the presence and absence of synthetic androgen R1881. Overexpressing TMPRSS2-ERG fusions in LNCaP cells downregulated PSMA both in the presence or absence of R1881, while overexpressing wild type ERG did not. Using PSMA-based luciferase reporter assays, we found TMPRSS2-ERG fusion can inhibit PSMA activity at the transcriptional level. Our data indicated that downregulation of PSMA in androgen-treated VCaP cells appears partially mediated by TMPRSS2-ERG gene fusion.

Introduction: Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-bactivated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. Methods: Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays. Results: Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. Discussion: Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH. [ABSTRACT FROM AUTHOR]