[Preliminary Study on the Relationship between the Developmental Stage of Multiple Myeloma Disease and the Results of Bone Marrow Whole Exome Sequencing].

OBJECTIVE: To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients. METHODS: Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened. RESULTS: Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution. CONCLUSION: different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.

Transcriptomics-based investigation of manganese dioxide nanoparticle toxicity in rats' choroid plexus.

Manganese dioxide nanoparticles (MnO2-NPs) have a wide range of applications in biomedicine. Given this widespread usage, it is worth noting that MnO2-NPs are definitely toxic, especially to the brain. However, the damage caused by MnO2-NPs to the choroid plexus (CP) and to the brain after crossing CP epithelial cells has not been elucidated. Therefore, this study aims to investigate these effects and elucidate potential underlying mechanisms through transcriptomics analysis. To achieve this objective, eighteen SD rats were randomly divided into three groups: the control group (control), low-dose exposure group (low-dose) and high-dose exposure group (high-dose). Animals in the two treated groups were administered with two concentrations of MnO2-NPs (200 mg kg-1 BW and 400 mg kg-1 BW) using a noninvasive intratracheal injection method once a week for three months. Finally, the neural behavior of all the animals was tested using a hot plate tester, open-field test and Y-type electric maze. The morphological characteristics of the CP and hippocampus were observed by H&E stain, and the transcriptome of CP tissues was analysed by transcriptome sequencing. The representative differentially expressed genes were quantified by qRT-PCR. We found that treatment with MnO2-NPs could induce learning capacity and memory faculty decline and destroy the structure of hippocampal and CP cells in rats. High doses of MnO2-NPs had a more obvious destructive capacity. For transcriptomic analysis, we found that there were significant differences in the numbers and types of differential genes in CP between the low- and high-dose groups compared to the control. Through GO terms and KEGG analysis, high-dose MnO2-NPs significantly affected the expression of transporters, ion channel proteins, and ribosomal proteins. There were 17 common differentially expressed genes. Most of them were transporter and binding genes on the cell membrane, and some of them had kinase activity. Three genes, Brinp, Synpr and Crmp1, were selected for qRT-PCR to confirm their expression differences among the three groups. In conclusion, high-dose MnO2-NPs exposure induced abnormal neurobehaviour, impaired memory function, destroyed the structure of the CP and changed its transcriptome in rats. The most significant DEGs in the CP were within the transport system.

[Expression and Significance of PD-1, PD-L1 and CTLA-4 in the Bone Marrow of Patients with Multiple Myeloma].

OBJECTIVE: To study the expression and significance of PD-1, PD-L1 and CTLA-4 tumor-associated antigens in multiple myeloma. METHODS: Bone marrow specimens from 122 patients with multiple myeloma were collected and divided into new-onset group (NDMM), complete remission group (CRMM) and relapsed and refractory group (RRMM) according to the disease progression stage. The proportion of CD4+ T lymphocytes, CD8+ T lymphocytes, Treg cells and plasma cells in the specimens and the expressions of PD-1, PD-L1 and CTLA-4 were detected by multi-parameter flow cytometry. RESULTS: There was no significant difference in the proportion of CD8+T and Treg cells among the three groups (P>0.05), while the proportions of CD4+T cells and PC in NDMM group were significantly higher than those in the CRMM group (P<0.05), the ratios of CD4+ to CD8+T in the NDMM and RRMM groups were significantly higher than those in the CRMM group (P<0.05). The expressions of PD-1, PD-L1 and CTLA-4 in CD8+ T cells was no significant difference among NDMM, CRMM and RRMM groups (P>0.05). While the expressions of PD-1, PD-L1 and CTLA-4 in CD4+ T cells and PC in the NDMM group were significantly lower than that in the CRMM group (P<0.05). There was significantly difference among the three groups in the expression of PD-1 in Treg cells, of which the NDMM group was significantly lower than that of the CRMM group (all P<0.05). The expressions of PD-1 and CTLA-4 in PC were significantly higher than those in CD8+ T, CD4+ T and Treg cells (P<0.05), the expression of PD-L1 in CD8+ T cells was significantly higher than that in CD4+ T and Treg cells (P<0.05). CONCLUSION: There is a correlation between the immune status of multiple myeloma and the expressions of PD-1, PD-L1 and CTLA-4 in plasma cells and lymphocyte subsets in vivo.

Pulmonary Fibrosis Induced by CdSe Nanorods and the Therapy with Modified Procyanidinere.

The CdSe nanorod as a one-dimensional nanostructure has an excellent performance in many fields, such as healthcare, new energy, and environmental protection. Thus, it is crucial to investigate its potential adverse health effects prior to their wide exposure. The lung tissue would be the main target organ after CdSe nanorods enter living systems. Here, we showed that pulmonary instillation of CdSe nanorods could decrease the vitality of T-SOD and T-AOC in lung tissues of a rat, increase MDA and hydroxyproline levels and lipid peroxidation products, induce mitochondrial cristae breakage and vacuolization, cause inflammatory responses, and finally induce pulmonary fibrosis. The oral administration of modified procyanidinere could significantly increase the content of antioxidant enzymes, scavenge free radicals, reduce lipid peroxidation, and have protective effects on CdSe nanorods-induced pulmonary fibrosis. The benefit is not only in the early inflammatory stage but also in the later stages of the CdSe nanorods-induced pulmonary fibrosis.

[Application of CD138 Immunomagnetic Bead Sorting Combined with Fluorescence in Situ Hybridization in Multiple Myeloma].

OBJECTIVE: To compare the effects of direct fluorescence in situ hybridization (D-FISH) detection without sorting and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) on cytogenetic analysis of patients with multiple myeloma (MM). METHODS: FISH test results of 229 patients with initial MM were retrospectively analyzed. The patients were divided into two groups, 140 patients were tested with D-FISH and 89 patients with MACS-FISH. The combination probe was designed as P53, D13S319, RB1, 1q21, and IgH. Cytogenetic detection results were compared between the two groups. RESULTS: The total detection rate of cytogenetic abnormalities in D-FISH group was 52.9%, and that in MACS-FISH group was 79.8%. There was a significant difference in the cytogenetic abnormality rate between the two groups (P=0.020). The abnormal genes with the highest detection rate in the two groups were 1q21 and IgH, respectively, while the lowest was P53. There was no significant difference in the percentage of P53 positive cells (positive rate) between the two groups, while D13S319, RB1, 1q21, and IgH showed significant difference in positive cell rate (P=0.0002, P<0.0001, P=0.0033, P=0.0032). There was no significant correlation between the proportion of plasma cells (PC) detected by bone marrow morphology and cytogenetic abnormality rate in the D-FISH group, while there was a correlation between the proportion of PC detected by flow cytometry and cytogenetic abnormality rate (r=0.364). The PC proportion detected by bone marrow morphology and flow cytometry in the MACS-FISH group had no correlation with the cytogenetic abnormality rate and positive cell rate of the 5 genes mentioned above. Additionally, the PC proportion detected by bone marrow morphology and flow cytometry showed significant difference (P<0.0001). CONCLUSION: CD138 immunomagnetic bead sorting combined with FISH technology can significantly improve the abnormality detection rate of MM cytogenetics.

Effect and Mechanism of PINK1/Parkin-Mediated Mitochondrial Autophagy in Rat Lung Injury Induced by Nano Lanthanum Oxide.

Nano lanthanum oxide particles (La2O3 NPs) are important nanoparticle materials which are widely used in photoelectric production, but their potential health hazards to the respiratory system are not clear. The purpose of this study was to explore the possible mechanism of lung injury induced by La2O3 NPs. In this study, 40 SPF male SD rats were randomly divided into low-, medium-, and high-dose groups and control groups, with 10 animals in each group. Rats were poisoned by tracheal injection. The low-, medium-, and high-dose groups were given La2O3 NPs suspension of 25, 50, and 100 mg/kg, respectively, and the control group was given an equal volume of high-temperature sterilized ultrapure water. The rats in each group were exposed once a week for 12 consecutive times. The gene transcription and protein expression levels of PINK1 and parkin in rat lung tissue were mainly detected. Compared with the control group, the gene transcription and protein expression levels of PINK1 and Parkin in the exposed group were significantly higher (p < 0.05). La2O3 NPs may activate PINK1/parkin-induced mitochondrial autophagy.

Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes.

Cadmium sulfide quantum dots (CdS QDs) are being developed for sensors, fluorescent probes, and other platforms and are attracting increasing attention. Given the growing demand for QDs, it is clear that there is a need to understand their potential toxicity to organisms. However, little is known regarding the genotoxicity of CdS QDs to humans. Therefore, this study used CdS QDs as the research object, cultured human peripheral blood lymphocytes, and randomly divided them into a control group, CdS I group (CdS QDs), and CdS II group (CdS QDs coated with thioglycolic acid). After cultivation, we measured the olive tail distance, tail length, tail DNA%, lymphocyte micronucleus rate, and aneuploid rate. The comet test results indicated that the indices of the QD group were significantly larger than those of the control group (P < 0.05). The results of the micronucleus and chromosome aberration tests showed that the lymphocyte micronucleus rate and chromosome aneuploid rate in the QD group were significantly increased (P < 0.05) compared with those in the control group. In conclusion, CdS QDs have certain genotoxicity to human peripheral blood lymphocytes, and the DNA damage caused by CdS QDs encapsulated with thioglycolic acid is less severe than that caused by nonencapsulated CdS QDs.

Ecological and health risk assessment of heavy metals in soil and Chinese herbal medicines.

As medicinal plants can accumulate harmful metals from the native soil, people's consumption of these materials may cause the human body to accumulate toxic metal elements. This has given rise to people's concerns about the quality and safety of Chinese medicinal materials. This research aims to determine the levels of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in four medicinal plant species (Aster tataricus L.f., Salvia miltiorrhiza Bge, Radix Aucklandiae, Scutellaria baicalensis Georgi) and their native soil. All samples were collected from Qian'an city, beside Yanshan Mountain Range in Tangshan city, east Hebei Province, north China. The contents of heavy metals we detected in the soil conformed to the current limits. However, the Cd and Hg in the soil had a very high potential ecological risk because of their contents higher than the base level of local soil. The contents of Cu, Cd, Hg and Pb in some medicinal herbs exceeded the standards. The content of Cu in Radix Aucklandiae exceeded the standard by 3 times, and others exceeded the standard by less than one time. The comprehensive health risk assessment of heavy metals with chronic non-carcinogenic effects for human body showed that none of the four medicinal herbs can create a health risk. Thus, there is no strong positive correlation between heavy metal pollution in medicinal herbs and that in the native soil. Further research should be investigated to the connection between the heavy metal levels in the soil and plants, and the comprehensive effects of soil, air and irrigation water on heavy metal pollution of Chinese herbal medicines. We also recommend that Chinese herbal medicines should be cultivated and gathered only from controlled or uncontaminated areas.

miR-30e-5p Regulates Autophagy and Apoptosis by Targeting Beclin1 Involved in Contrast-induced Acute Kidney Injury.

AIMS: This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CIAKI). METHODS: Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription-polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl- tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal- deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. RESULTS: HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. CONCLUSION: Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.

Prevalence and genotype distribution of HPV infection among 214,715 women from Southern China, 2012-2018: baseline measures prior to mass HPV vaccination.

BACKGROUND: The epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination. METHODS: A retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People's Hospital for cervical screening during 2012-2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed. RESULTS: The overall HPV prevalence was 18.71% (95% confidence interval [CI], 18.55-18.88%) among Southern China females. During 2012-2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07-22.20%) in 2012 to 18.75% (95% CI, 18.35-19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13-35.15%), 20.07% (95% CI, 19.70-20.44%) among women aged 21-30 years, 17.29% (95% CI, 17.01-17.57%) among women aged 31-40 years, 17.23% (95% CI, 16.95-17.51%) among women aged 41-50 years, 21.65% (95% CI, 21.11-22.20%) among women aged 51-60 years, and 25.95% (95% CI, 24.86-27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11-22.20%), - 16 (2.96%; 95% CI, 2.89-3.03%), and - 58 (2.51%; 95% CI, 2.44-2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80-1.92%) and - 6 (0.69%; 95% CI, 0.66-0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study. CONCLUSIONS: This study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012-2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, - 16 and - 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.

Breakpoint mapping of a t(9;22;12) chronic myeloid leukaemia patient with e14a3 BCR-ABL1 transcript using Nanopore sequencing.

BACKGROUND: The genetic changes in chronic myeloid leukaemia (CML) have been well established, although challenges persist in cases with rare fusion transcripts or complex variant translocations. Here, we present a CML patient with e14a3 BCR-ABL1 transcript and t(9;22;12) variant Philadelphia (Ph) chromosome. METHODS: Cytogenetic analysis and fluorescence in situ hybridization (FISH) was performed to identify the chromosomal aberrations and gene fusions. Rare fusion transcript was verified by a reverse transcription-polymerase chain reaction (RT-PCR). Breakpoints were characterized and validated using Oxford Nanopore Technologies (ONT) (Oxford, UK) and Sanger sequencing, respectively. RESULTS: The karyotype showed the translocation t(9;22;12)(q34;q11.2;q24) [20] and FISH indicated 40% positive BCR-ABL1 fusion signals. The RT-PCR suggested e14a3 type fusion transcript. The ONT sequencing analysis identified specific positions of translocation breakpoints: chr22:23633040-chr9:133729579, chr12:121567595-chr22:24701405, which were confirmed using Sanger sequencing. The patient achieved molecular remission 3 months after imatinib therapy. CONCLUSIONS: The present study indicates Nanopore sequencing as a valid strategy, which can characterize breakpoints precisely in special clinical cases with atypical structural variations. CML patients with e14a3 transcripts may have good clinical course in the tyrosine kinase inhibitor era, as reviewed here.

Protective effect of astaxanthin against La2O3 nanoparticles induced neurotoxicity by activating PI3K/AKT/Nrf-2 signaling in mice.

Lanthanum oxide nanoparticles (La2O3 NPs) are used in photoelectric and catalytic applications. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant and anti-inflammatory properties, and the antioxidant activities promote neuroprotection. This study explored the effect of ASX supplementation on La2O3 NP-induced neurotoxicity in mice and the molecular mechanisms of such protective effects. Amongst our findings, we determined that ASX treatment significantly attenuated La2O3 NP-induced behavioural abnormalities, histopathological evidence of hippocampal injury and ultrastructural changes in the CA1 region of the hippocampus. ASX treatment also markedly inhibited the production of ROS and activated PI3K/AKT signaling, which facilitated the nuclear translocation of Nrf-2 and reversed the down-regulation of HO-1, NQO1 and GCLM proteins in the hippocampus that were induced by sub-chronic exposure to La2O3 NPs. Administration of ASX to mice receiving La2O3 NPs also resulted in decreased expression of iNOS, IL-1ß, TNF-α, COX-2, Bax and Caspase-3 and in increased expression of BDNF, NGF and Bcl-2 observed in response to La2O3 NPs. In conclusion, ASX had a markedly protective effect against the negative sequelae associated with La2O3 NP-induced neurotoxicity. This may result from the activation of the PI3K/AKT/Nrf-2 signaling and via the inhibition of oxidative stress, neuroinflammation and cellular apoptosis.

La2O3 Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice.

PURPOSE: Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in catalytic and photoelectric applications, but the reproductive toxicity is still unclear. This study evaluated the reproductive toxicity of two different-sized La2O3 particles in the testes. MATERIALS AND METHODS: Fifty Kunming mice were randomly divided into five groups. Mice were treated with La2O3 NPs by repeated intragastric administration for 90 days (control, nano-sized with 5, 10, 50 mg/kg BW and micro-sized with 50 mg/kg BW). Mice in the control group were treated with de-ionised water without La2O3 NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated. RESULTS: The body weight of mice treated with La2O3 NPs or not had no difference; sperm parameters and histological assessment showed that La2O3 NPs could induce reproductive toxicity in the testicle. Serum testosterone and gonadotropin-releasing hormone (GnRH) in the NH (nano-sized with 50 mg/kg BW) group were markedly decreased relative to control group, and an increase of luteinizing hormone (LH) in NH group was detected . Additionally, transmission electron microscopy revealed that the ultrastructural abnormalities induced by La2O3 NPs were more severe than La2O3 MPs in the testes. Furthermore, La2O3 NPs treatment inhibited the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm into the nucleus as well as the expression of downstream genes NAD(P)H quinone oxidoreductase1 (NQO1), hemeoxygenase 1 (HO-1) and (glutathione peroxidase) GSH-Px, thus abrogating Nrf-2-mediated defense mechanisms against oxidative stress. CONCLUSIONS: The results of this study demonstrated that La2O3 NPs improved the spermatogenesis defects in mice. La2O3 NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.

Prevalence and pollution characteristics of antibiotic resistant genes in one high anthropogenically-impacted river.

The objectives of this study were to comprehensively investigate the occurrence, distribution, and mobility of antibiotic resistant genes (ARGs) in the biofilm, water, and sediment from a section of the Weihe-river, in the northern Henan province, China. The abundances of nine ARGs belonging to four commonly used antibiotic classes (tetracyclines, sulfonamides, fluoroquinolones, and multidrug) and class 1 integron-integrase gene (intI1) were quantified. Sulfonamides gene (sulI) accounted for the highest percentage of detected ARGs in most sampling sites, including in water, biofilm, and sediment. Among the resistance genes, IntI1 and sul1 were significantly correlated (r>0.800, p<0.01) with a fecal coliform (FC) detected in the biofilm, and there was also a significantly positive correlation between the abundances of 16SrRNA and intI1 in the biofilms. Compared with the sediment and water samples, the biofilms contained sufficient nutrients to promote bacterial reproduction. Under sufficient total nitrogen and phosphorus concentrations, the horizontal gene transfer due to intI1 plays a key role in the formation and migration of ARGs within biofilms.

Activation of Nrf2 by lead sulfide nanoparticles induces impairment of learning and memory.

Lead sulfide nanoparticles (PbS NPs) are semiconductor materials that have been widely applied to light-emitting diodes (LEDs), biological fluorescent probes, infrared detection, solar receivers, ion-selective electrodes, and ion-sensitive materials. However, the effects of PbS NPs on the central nervous system are still unclear. Thus, this study aimed to determine, using rats, the mechanism of action of PbS NPs, exposure to which results in persistent alterations in nervous system function. The results of the Morris water maze test showed that PbS NPs significantly impaired learning and memory. Compared with that in the control group, the lead content in the hippocampal tissue was significantly elevated after PbS NP exposure. Exposure to PbS NPs led to increased oxidative damage in blood and hippocampal tissues, and significantly inhibited the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) while increasing the serum malondialdehyde (MDA) content. In addition, reactive oxygen species triggered the activation of Nrf2 and the antioxidant system, including HO-1, r-GCS, and GSH-Px. Moreover, we observed significant apoptosis in the hippocampi of the rats using the TUNEL assay and transmission electron microscopy. The MOD values from the TUNEL assay of the hippocampi were all significantly higher than those of the control group, which increased as the concentration of the PbS NPs increased. There were also changes in the ultrastructure of the hippocampal neurons and synapses in the PbS-treated rats, including a shorter synaptic active zone, smaller curvature of the synaptic interface, and thicker postsynaptic density. Therefore, PbS NP exposure could lead to increased brain lead content, oxidative damage, and apoptosis.

Exposure to PbSe Nanoparticles and Male Reproductive Damage in a Rat Model.

PbSe nanoparticles (PbSe-NPs) attract ever-growing interest owing to their great promise in various fields. However, potential toxic effects of PbSe-NPs on male reproductive systems have not been reported. This study aimed to determine whether early-life exposure to PbSe-NPs could affect male reproductive systems and other related health effects in rats. The male rats were intraperitoneally injected with 10 mg/kg/week PbSe-NPs for 60 days followed by a series of reproductive-related analyses. We found that the nanoparticles could accumulate in testes in a size-dependent manner. Furthermore, accumulation of PbSe-NPs resulted in oxidative stress and disorder of normal serum sex hormones. Endoplasmic reticulum and mitochondria-mediated cell apoptosis were triggered via oxidative stress, as shown by upregulation of cytoplasmic Cyt-c, Bax, cleaved Caspase-3, GRP78, and Caspase-12. Notably, PbSe-NP administration led to reduction in the quantity and quality of sperm, which caused a great fertility decrease. In contrast, released Pb2+ from PbSe-NPs did not result in any testis toxicity and fertility declines. These results demonstrate that PbSe-NPs could cause severe reproductive toxicity in a size-dependent manner and these toxic effects should be responsible for PbSe-NPs themselves rather than released Pb2+. The application of PbSe-NPs might be a double-edged sword, and corresponding measures should be taken before use.

Resveratrol alleviate the injury of mice liver induced by cadmium sulfide nanoparticles.

Cadmium sulfide nanoparticle (Nano-CdS) is a kind of important semiconductor material with special photochemistry property. With the Nano-CdS being widely used, the security problems it caused have been catching more and more attention. This study aims to explore the possible mechanism of liver injury induced by Nano-CdS and whether resveratrol can reduce the damage. In this study, male BALB/C mice were treated with Nano-CdS with a diameter of 20 to 30 nm and a length of 80 to 100 nm. It turned out that the mice liver inflammatory cells infiltrated, the liver tissue and the ultrastructure changed; The activities of T-AOC and GSH were suppressed (n = 6, P < 0.05) and the content of lipid peroxide (MDA) increased (n = 6, P < 0.05). Besides, Nano-CdS decreased the mRNA expression level of Sirt1 and FoxO1 genes in liver tissue (n = 3, P < 0.05). All the changes in the index were reversed by resveratrol. The mRNA expression level of FoxO3a showed no significant difference between the control group and the Nano-CdS group. But under the protection of resveratrol, the mRNA expression level of FoxO3a was higher than that in the control and Nano-CdS groups (n = 3, P < 0.05). Results suggest that Nano-CdS can cause oxidative damages to liver tissues in mice, in which process that the Sirt1 and FoxO1 genes may participate, and the damage can be reversed by resveratrol which may be a potential cure for oxidative damage to nanomaterials.

Neurotoxicity, behavioral changes and gene-expression profile of mice exposed to SnS2 nanoflowers.

Recently, interest in the potential applications of tin disulphide nanoflowers (SnS2 NFs) in the treatment of waste water and their antibacterial properties has increased. However, their effects on neurotoxicity, brain cognition and behavioural injury, as well as the underlying mechanisms of these effects have remained unknown. In the present study, we compared the neurotoxicity of SnS2 NFs (50 nm) administered intragastrically at different doses (5, 10, and 50 mg kg-1) in mice for 60 days. The results showed that the neurotoxicity of SnS2 NFs in mice is dose-dependent. Furthermore, expression levels of genes related to oxidative stress, metabolism and signal transduction were also modified in the brain tissues of mice exposed to SnS2 NFs, supporting the SnS2 NF-dependent neurotoxic phenotype. Additionally, SnS2 NF exposure resulted in an abnormal ultrastructure in the hippocampus of the treated mice. Nevertheless, their body weight, organ coefficient and behaviour assessed in an open-field test and learning and memory test results assessed using a Morris water maze test remained unaffected. This suggested that the increased risk of neurotoxicity in SnS2 NF-treated mice was dependent on the dosage of SnS2 NFs. The relative level of safety was <5 mg kg-1 for 50 nm SnS2 NFs. The present study provides an experimental basis for the safe application of SnS2 NFs; however, chronic behavioural effects of SnS2 NFs remain unknown.

The neurotoxicity induced by PM2.5 might be strongly related to changes of the hippocampal tissue structure and neurotransmitter levels.

Objective: The complex components of PM2.5 including metal elements transported through the blood brain barrier could induce nervous system damage. This study discusses the relationship between rats' learning and memory and changes in the hippocampal neuron histomorphology and neurotransmitter levels induced by PM2.5 exposure. Methods: Male rats were treated with different concentrations of PM2.5 by tracheal perfusion once per week for up to 12 weeks. After the rats were sacrificed, the main metal element contents (Al, Pb, Cu, Mn, As, Cr, Cd, and Ni) of the blood and whole hippocampus, levels of neurotransmitters released in the whole hippocampus and relative receptors, and changes in the hippocampal structure were detected. Results: The results showed that PM2.5 significantly reduced the cognitive learning abilities of rats. PM2.5 exposure increased the contents of hippocampal lead, manganese, and aluminum. The level of glutamic acid was increased in the hippocampal tissues of the 20 mg kg-1 group, in combination with the decreased N-methyl-d-aspartate glutamate receptor (NMDAR) and increased metabotropic glutamate receptor type1 (mGluR1) expression. Increased clearance, a mild disorder of arrangement, and mild edema could be observed in the rat hippocampal neurons treated with PM2.5. Conclusion: PM2.5-induced defects in learning and memory may be related to the morphological abnormalities of the hippocampus and the abnormal expression of neurotransmitters and their receptors.