A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

HIF-1α/m6A/NF-κB/CCL3 axis-mediated immunosurveillance participates in low level benzene-related erythrohematopoietic development toxicity.

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.

Polystyrene micro- and nanoplastics induce gastric toxicity through ROS mediated oxidative stress and P62/Keap1/Nrf2 pathway.

Microplastics (MPs) exist widely in the environment and can enter the human body indirectly through the food chain or directly through inhalation or ingestion. The primary organ that MPs contaminated food or water enters the human body through the digestive tract is the stomach. However, at present, the effects of MPs on the stomach and the related mechanism remain unclear. In this study, our results indicated that 50 nm and 250 nm polystyrene MPs (PS-MPs) at environmental related dose significantly decreased stomach organ coefficient, inhibited gastric juice secretion and mucus secretion, disrupted gastric barrier function and suppressed antioxidant ability in mice. In vitro experiments showed that PS-MPs inhibited cell viability, increased ROS generation, and induced apoptosis through mitochondria-dependent pathway. Simultaneously, PS-MPs also decreased mitochondrial membrane potential, ATP level, disrupted mitochondrial kinetic homeostasis, and activated P62 / Nrf2 / Keap1 pathway. Furthermore, blocking ROS (NAC) partially alleviated ROS and apoptosis caused by PS-MPs. Based on above findings, the potential adverse outcome pathway (AOP) of PS-MPs-caused gastric toxicity was proposed which provides a new insight into the risk assessment of MP related gastric damage. Our study unveils the gastric injury induced by PS MPs is dependent on ROS - mediated P62 / Nrf2 / Keap1 signaling pathway, and provides scientific basis for further exploration the mechanism of gastric toxicity of PS MPs.

Metabolic risk factors link unhealthy lifestyles to the risk of colorectal polyps in China.

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.

Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease.

Excessive accumulations of reactive oxygen species (ROS) and amyloid-ß (Aß) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aß fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aß fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood-brain barrier penetration and Aß binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aß plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aß deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.

Effects of tri-n-butyl phosphate (TnBP) on neurobehavior of Caenorhabditis elegans.

As an emerging flame retardant, organic phosphate flame retardants have been extensively used worldwide. The aim of this study is to determine the effects of TnBP on neurobehavior of Caenorhabditis elegans (C. elegans) and its mechanisms. L1 larvae of wild-type nematodes (N2) were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours. Then, we observed that the body length and body width were inhibited, the head swings were increased, the pump contractions and chemical trend index were reduced, the production of reactive oxygen species (ROS) was increased, and the expression of mitochondrial oxidative stress related genes (mev-1 and gas-1) and P38 MAPK signal pathway-related genes (pmk-1, sek-1, and nsy-1) was altered. After reporter gene strains BZ555, DA1240, and EG1285 were exposed to TnBP of 0, 0.1, 1, 10, and 20 mg/L for 72 hours, the synthesis of dopamine, glutamate, and Gamma-Amino Butyric Acid (GABA) was increased. In addition, the pmk-1 mutants (KU25) led to the sensitivity of C. elegans to TnBP in terms of head swings. The results showed that TnBP had harmful effects on the neurobehavior of C. elegans, oxidative stress might be one of the mechanisms of its neurotoxicity, and P38 MAPK signal pathway might play an important regulatory role in this process. The results revealed the potential adverse effects of TnBP on the neurobehavior of C. elegans.

Characterization of lymphocyte subsets and intestinal short-chain fatty acids in benzene-induced immunosuppressive mice.

Exposure to benzene causes immunosuppression, but the mechanism has not been clarified. In this study, mice were subcutaneously injected with different concentrations (0, 6, 30 and 150 mg/kg) of benzene for four weeks. The lymphocytes of bone marrow (BM), spleen and peripheral blood (PB) and the level of short-chain fatty acids (SCFAs) in mouse intestine were measured. The results showed that benzene exposure led to a reduction in CD3+ and CD8+ lymphocytes in mouse BM, spleen and PB, and CD4+ lymphocytes were increased in mouse spleen but decreased in mouse BM and PB after 150 mg/kg benzene exposure. In addition, Pro-B lymphocytes were reduced in mouse BM in the 6 mg/kg group. Besides, the levels of IgA, IgG, IgM, IL-2, IL-4, IL-6, IL-17a, TNF-α and IFN-γ in mouse serum were reduced after benzene exposure. Furthermore, the levels of acetic, propionic, butyric and hexanoic acid were reduced in mouse intestine, and the AKT-mTOR signaling pathway was activated in mouse BM cells after benzene exposure. Our results demonstrate that benzene induced immunosuppression in mice, and the B lymphocytes in BM are more sensible to benzene-induced toxicity. The reduction in mouse intestinal SCFAs as well as the activation of AKT-mTOR signaling may be related to the occurrence of benzene immunosuppression. Our study provides new insight for further mechanistic research on benzene-induced immunotoxicity.

Research progress on the cellular toxicity caused by microplastics and nanoplastics.

Microplastics (MPs) are plastic particles of a diameter of less than 5 mm and a major carrier of pollution. In accordance with its diameter range, MPs can be divided into microplastics (100-5 mm) and nanoplastics (<100 nm). In recent years, in addition to the impact of MPs on the environment, the ways in which MPs affect the body has also attracted continuous attention. However, relevant studies on the cytotoxicity of MPs are not comprehensive. Based on the current research, this paper summarizes four main cytotoxic mechanisms of MPs, inducing oxidative stress, damaging cell membrane organelles, inducing immune response, and genotoxicity. Generally, MPs cause cytotoxicity such as oxidative stress, damage to cell membranes and organelles, activation of immune responses, and genotoxicity through mechanical damage or induction of cells to produce reactive oxygen species. Understanding these toxic mechanisms is helpful for the evaluation and prevention of human toxicity of MPs. This paper also analyzes the limitations of current research and prospects for future research into cellular MPs, with the aim of providing a scientific basis and reference for further research into the toxic mechanism of MPs.

Research advances of microplastics and potential health risks of microplastics on terrestrial higher mammals: a bibliometric analysis and literature review.

Microplastics (MPs) have become increasingly serious global problems due to their wide distribution and complicated impacts on living organisms. To obtain a comprehensive overview of the latest research progress on MPs, we conducted a bibliometric analysis combined with a literature review. The results showed that the number of studies on MPs has grown exponentially since 2010. Recently, the hotspot on MPs has shifted to terrestrial ecosystems and biological health risks, including human health risks. In addition, the toxic effects, identification and quantification of MPs are relatively new research hotspots. We subsequently provide a review of MPs studies related to health risks to terrestrial higher mammals and, in particular, to humans, including detection methods and potential toxicities based on current studies. Currently, MPs have been found existing in human feces, blood, colon, placenta and lung, but it is still unclear whether this is associated with related systemic diseases. In vivo and in vitro studies have demonstrated that MPs cause intestinal toxicity, metabolic disruption, reproductive toxicity, neurotoxicity, immunotoxicity through oxidative stress, apoptosis and specific pathways, etc. Notably, in terms of combined effects with pollutants and neurotoxicity, the effects of MPs are still controversial. Future attention should be paid to the detection and quantification of MPs in human tissues, exploring the combined effects and related mechanisms of MPs with other pollutants and clarifying the association between MPs and the development of pre-existing diseases. Our work enhances further understanding of the potential health risks of MPs to terrestrial higher mammals.

Microplastics induce neurotoxicity in aquatic animals at environmentally realistic concentrations: A meta-analysis.

Microplastics (MPs) draw international attention owing to their widespread distribution in water ecosystems, but whether MPs cause neurotoxic effects in aquatic animals at environmentally realistic concentrations is still controversial. This meta-analysis recompiled 35 studies to determine whether MPs could change the levels of brain (in vivo) neurotransmitters in aquatic animals at environmentally realistic concentrations (≤1 mg/L, median = 0.100 mg/L). Then, a group comparison was conducted to compare the effects of different factors on the effect size and to explore the significant factors affecting the neurotoxicity of MPs. The results demonstrated that MP exposure could considerably decrease the levels of acetylcholinesterase (AchE) in the brain of aquatic animals by 16.2%. However, the effects of MPs on cholinesterase (CHE), acetylcholine (ACh), dopamine (DA) and γ-aminobutyric acid (GABA) were not statistically significant due to the small number of studies and samples. The neurotoxicity of MPs was closely linked with particle size and exposure time but independent of animal species, MP compositions, MP morphology and MP concentrations. Further literatures review indicated that MP-induced neurotoxicity and behavioral changes are related with multiple biological processes, including nerve damage, oxidative stress, intestinal flora disturbance and metabolic disorder. Furthermore, some factors influencing MP neurotoxicity in the real environment (e.g. the aging of MPs, the release of MP additives, and the co-exposure of MPs and pollutants) were discussed. Overall, this study preliminarily explored whether MPs induced changes in neurotoxicity-related indicators in aquatic animals through meta-analysis and provided scientific evidence for evaluating the health risks and neurotoxicity of MPs at the environmental level.

CIRCKLHL2 KNOCKDOWN ALLEVIATES SEPSIS-INDUCED ACUTE LUNG INJURY BY REGULATING MIR-29B-3P MEDIATED ROCK1 EXPRESSION DOWN-REGULATION.

ABSTRACT: Background: Acute lung injury (ALI) induced by sepsis is distinguished by an inflammatory progression. Herein, we investigated the action of circular RNA kelch like family member 2 (circKlhl2) in sepsis-induced ALI. Methods: The animal or cell model of sepsis ALI was established by LPS stimulation. The contents of circKlhl2, microRNA-29b-3p (miR-29b-3p), rho-associated coiled-coil containing protein kinase 1 (ROCK1), CyclinD1, B-cell lymphoma-2 (Bcl-2), and cleaved-caspase 3 (C-caspase-3) were detected by quantitative real-time polymerase chain reaction and western blot, respectively. Cell viability was assessed by cell counting kit 8 assay. Cell cycle and apoptosis were evaluated by flow cytometry. The abundances of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay. Besides, the targeted relationship between miR-29b-3p and circKlhl2 or ROCK1 was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Results: Loss of circKlhl2 mitigated lung injury and proinflammatory cytokine expression in sepsis-ALI mice model and alleviated LPS-induced apoptosis and inflammatory response in microvascular endothelial cell (MPVECs) in vitro . The abundances of circKlhl2 and ROCK1 were boosted, while the miR-29b-3p level was diminished in the animal or cell model of sepsis-ALI. MiR-29b-3p inhibition abrogated circKlhl2 knockdown-mediated effects on MPVECs injury. Moreover, miR-29b-3p overexpression promoted cell proliferation and inhibited apoptosis and inflammation in LPS-treated MPVECs, while ROCK1 enhancement reversed these effects. Conclusion: CircKlhl2 expedited the sepsis-induced ALI by adjusting miR-29b-3p/ROCK1 axis.

Let-7e-5p, a promising novel biomarker for benzene toxicity, is involved in benzene-induced hematopoietic toxicity through targeting caspase-3 and p21.

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.

Microcystin-LR exposure enhances toxin-degrading capacity and reduces metabolic diversity of sediment microbial communities.

Substantial outbreaks of cyanobacterial harmful algal blooms (cyanoHABs) are accompanied by the prevalent existence of microcystins (MCs) in eutrophic freshwater worldwide, which can compromise the safety of aquatic ecosystems and public health. However, the response of the sediment microbial community to MCs exposure remains unclear. In this study, the sediment microbial communities of Lake Taihu were continuously exposed to environmentally relevant concentration (10 µg/L) of microcystin-LR (MC-LR) in microcosms for three months to mimic MCs contamination during cyanoHABs. Meanwhile, the MC-LR degradation characteristics, metabolic profiles, functional genes, and structures of microbial communities were analyzed periodically. The results showed that the MC-LR degradation capacities of microbial communities significantly increased with prolonged toxin exposure time. The enhanced MC-LR degradation rate was positively correlated with the increase in the abundance of mlr genes, which corresponds to the MC-degrading bacterial community. However, the MC-LR degradation pathway was maintained, and one new biodegradation intermediate (Adda-Glu) was first identified. Moreover, the metabolic profiles of the microbial communities indicated that overall carbon metabolic activity displayed a stimulation-suppression trend, and the exposure led to different carbon utilization patterns. Furthermore, microbial community structure analysis showed that long-term MC-LR exposure enriched microbes associated with MC degradation (Pseudomonas, Stenotrophomonas, Sphingopyxis and Sphingomonas) but inhibited MC-sensitive bacterial genera. This study clearly elucidates that MC-LR exposure alters the function, metabolism, and structure of the sediment microbial community to adapt to polluted environments.

High expression of HIF-1α alleviates benzene-induced hematopoietic toxicity and immunosuppression in mice.

Benzene exposure can cause pancytopenia and immunosuppression, leading to serious diseases such as aplastic anemia (AA) or acute myeloid leukemia (AML), but the underlying mechanism has not been fully elucidated. Hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that regulates many downstream target genes. In this study, we reported a novel mechanism by which high expression of HIF-1α alleviated benzene toxicity. Mice with high expression of HIF-1α (HIF-1α+) were obtained by the Tet-on system and doxycycline induction, and they and wild-type (WT) mice were exposed to 150 mg/kg benzene for 0, 1, 3, 7, 10, 14, and 28 days. Dynamic changes in hematopoietic and immune-related indicators and the role of HIF-1α were explored. The level of white blood cells in mice reached the highest level on the third day, and immunity was activated and then suppressed within 10 days. Significant pancytopenia and immunosuppression occurred at 14 days and were more pronounced at 28 days. The levels of HIF-1α, EPO, VEGF, RORγt, and IL-17 in WT mice gradually decreased with increasing benzene exposure days, while the levels of Foxp3 and IL-10 increased. These changes were alleviated in HIF-1α+ mice. High expression of HIF-1α increased the levels of EPO and VEGF, which helped to maintain the stability of the hematopoietic microenvironment. Simultaneously, it attenuated benzene-induced immunosuppression by alleviating the Th17/Treg imbalance. HIF-1α is expected to be a new target for benzene-induced diseases such as AA and AML.

Ferroptosis is involved in the benzene-induced hematotoxicity in mice via iron metabolism, oxidative stress and NRF2 signaling pathway.

Benzene is a pollutant that widely exists in the environment and in occupational workplaces. Its exposure is closely associated with hematological disorders and even leukemia, which poses a significant threat to public health. Thus, the underlying mechanisms should be explored. In the current study, it was investigated whether ferroptosis plays a role in benzene hematopoietic toxicity and related mechanisms. Mice were subcutaneously injected with benzene at 150 mg/kg b.w. to establish a hematotoxicity model. Four weeks later, the mice exposed to benzene exhibited a decrease in white blood cells, red blood cells, and hemoglobin level, as well as reduction in frequency of hematopoietic stem and progenitor cells (HS/PCs) and the colony forming abilities of CFU-G, CFU-M, CFU-GM, and CFU-GEMM. Simultaneously, apart from ferroptosis features in the mitochondrial morphology, decreased ATP and mitochondrial membrane potential, alterations in biochemical indices and gene expression were also observed, such as increased intracellular iron and lipid peroxidation, glutathione (GSH) depletion, and reduced glutathione peroxidase (GSH-Px) level, and upregulated PTGS2. Meanwhile, markedly altered expression of SLC7A11, GPX4, GCLC, NOX1, TFRC, FTH1, and FTL hinted that redox imbalance and dysfunction of iron uptake and storage are vital to induce ferroptosis. Additionally, decreased cytoplasmic NRF2 and increased nuclear NRF2 were also found, suggesting the activation of the NRF2 pathway. More importantly, inhibition of ferroptosis with ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially relieved the hematopoietic injuries. Our findings imply that dysregulation in the system Xc-/GPX4 axis, iron metabolism, and activation of the NRF2 pathway play a crucial role in benzene-induced ferroptosis, and reveals that taking ferroptosis as a target may be a potential intervention strategy for benzene-induced hematotoxicity.

Neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate in Caenorhabditis elegans.

As a new type of flame retardant, Organic Phosphate Flame Retardant has been widely used worldwide. The purpose of our research is to determine the neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate (TDCPP) to Caenorhabditis elegans and its mechanism. L1 larvae wild-type C. elegans were exposed to different concentrations of TDCPP, and the effects on motor behavior (head thrashes, body bends, pumping times, chemotaxis index), ROS levels, and p38MAPK signaling pathway-related gene expression levels were measured. Three transgenic nematode strains, BZ555, DA1240, and EG1285, were also used to study the effects of TDCPP on nematode dopamine neurons, glutamate neurons, and GABA neurons. The results showed that TDCPP can inhibit the head thrashes and body bends of the nematode, reduce dopamine production, increase the level of ROS in the body, and affect the expression of genes related to the p38MAPK signaling pathway. We next employed ROS production and motor behavior as toxicity assessment endpoints to determine the involvement of p38 MAPK signaling in the regulation of response to TDCPP. The results showed that the nematodes with low expression of pmk-1 were less sensitive to the TDCPP. It was suggested that TDCPP had neurotoxicity and regulated neurotoxicity to C. elegans by activating the p38-MAPK signaling pathway. The research in this article provides important information for revealing the environmental health risks of organophosphorus flame retardants and their toxic mechanism of action.

Effects of Serum C-Peptide Level on Blood Lipid and Cardiovascular and Cerebrovascular Injury in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis.

Objective: This study aims to investigate the effects of serum C-peptide levels on blood lipid and cardiovascular and cerebrovascular injury in patients with type 2 diabetes mellitus (T2DM). Methods: China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Web of Science, and Embase databases were searched for relevant studies published from January 2010 to June 2021. All retrieved randomized controlled trials that evaluated the effect of serum C-peptide levels on blood lipids or cardiovascular and cerebrovascular injuries in T2DM patients were included in our study. Patients in the included studies were divided into normal C-peptide group (control group) and low C-peptide group (treatment group) according to fasting C-peptide levels. Meta-analysis was performed using Stata16.0. Results: A total of 7 studies were included for the meta-analysis. Compared with the control group, the treatment group was associated with a higher incidence of coronary heart disease (OR = 4.89; 95% CI: 1.13, 21.24; P < 0.05) and cerebral infarction (OR = 3.24; 95% CI: 0.59, 17.66; P < 0.05). In addition, patients in the treatment group had significantly higher levels of total cholesterol (SMD = 0.01; 95% CI: -0.38, 0.39; P < 0.05), triglyceride (SMD = 0.62; 95% CI: 0.24, 1.00; P < 0.05), glycated hemoglobin (SMD = 0.25; 95% CI: -0.50, 1.00; P < 0.05), and low-density lipoprotein cholesterol (SMD = 0.23; 95% CI: -0.00, 0.46; P < 0.05). However, there was no significant difference in high-density lipoprotein cholesterol levels between the two groups (SMD = 0.30; 95% CI: -0.26, 0.86; P > 0.05). Conclusions: Low serum C-peptide level significantly increases the incidence of coronary heart disease and cerebral infarction. Additionally, low serum C-peptide increases blood lipid level and promotes lipid deposition. Collectively, low serum C-peptide has a negative impact on the occurrence and development of T2DM and therefore serum C-peptide level needs to be adjusted timely.

Hematological effects of glyphosate in mice revealed by traditional toxicology and transcriptome sequencing.

The herbicide glyphosate is being used worldwide. Hematological toxicity caused by glyphosate exposure has been reported, but the underlying mechanisms remain unclear. In this study, classical toxicology methods and RNA sequencing were performed to explore the molecular mechanisms related to glyphosate hematotoxicity. We found that 500 mg/kg b.w. glyphosate-based herbicide (GBH) significantly decreased leukocyte, neutrophil, lymphocyte and monocyte counts, as well as inhibited colony-forming abilities of CFU-GM, CFU-G and CFU-GEMM. RNA sequencing identified 82 and 48 differentially expressed genes (DEGs) in BM cells after treatment with 250 mg/kg and 500 mg/kg GBH, respectively. Meanwhile, GO and KEGG analyses revealed that the MAPK signaling pathway, hematopoietic cell lineage and cytokine-cytokine receptor interactions were vital pathways involved in GBH-induced toxicity in BM cells. Notably, Nr4a, Fos, Thbs1 and tnfrsf19 contributed to the hematotoxicity of GBH by regulating hematopoietic stem cell functions. In summary, our efforts enhance the understanding of the glyphosate hematotoxic responses and facilitate future studies on its corresponding mechanisms.