Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study.

BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

Pericarotid Adipose Tissue is Associated with Circulatory Markers of Inflammation and Carotid Atherosclerosis.

Perivascular adipose tissue plays roles in vascular inflammation and atherosclerosis. The present study aimed to evaluate the association between pericarotid fat density (PFD) and circulatory inflammatory indicators, internal carotid artery (ICA) stenosis, and vulnerable carotid plaques. We retrospectively screened 498 consecutive patients who underwent both computed tomography angiography of the neck between January 2017 and December 2020. The PFD, ICA stenosis, and vulnerable carotid plaques were analyzed using established approaches. Laboratory data including C-reactive protein (CRP) levels, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were recorded. PFD was positively correlated with CRP, NLR, PLR, and SII, and negatively correlated with LMR. A higher PFD was independently associated with extracranial ICA stenosis (1.179 [1.003-1.387], P = .040) and vulnerable carotid plaques (1.046 [1.021-1.072], P = .001) after adjusting for systemic inflammatory indicators. These findings suggested higher PFD is independently associated with circulating inflammatory indicators, extracranial ICA stenosis, and vulnerable carotid plaque.

MdTPR16, an apple tetratricopeptide repeat (TPR)-like superfamily gene, positively regulates drought stress in apple.

The Tetratricopeptide repeat (TPR)-like superfamily with TPR conserved domains is widely involved in the growth and abiotic stress in many plants. In this report, the gene MdTPR16 belongs to the TPR family in apple (Malus domestica). Promoter analysis reveal that MdTPR16 incorporated various stress response elements, including the drought stress response elements. And different abiotic stress treatments, drought especially, significantly induce the response of MdTPR16. Overexpression of MdTPR16 result in better drought tolerance in apple and Arabidopsis by up-regulating the expression levels of drought stress-related genes, achieving a higher chlorophyll content level, more material accumulation, and overall better growth compared to WT in the drought. Under drought stress, the overexpressed MdTPR16 also mitigate the oxidative damage in cells by reducing the electrolyte leakage, malondialdehyde content, and the H2O2 and O2- accumulation in apples and Arabidopsis. In conclusion, MdTPR16 act as a beneficial regulator of drought stress response by regulating the expression of related genes and the cumulation of reactive oxygen species (ROS).

Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism.

Background: Plant essential oils have long been regarded as repositories of antimicrobial agents. In recent years, they have emerged as potential alternatives or supplements to antimicrobial drugs. Although literature reviews and previous studies have indicated that cinnamon essential oil (CIEO) and its major component, cinnamaldehyde (CID), possess potent antibacterial activities, their antibacterial mechanisms, especially the in vivo antibacterial mechanisms, remain elusive. Methods: In this study, we utilized the in vivo assessment system of Caenorhabditis elegans (C. elegans) to investigate the effects and mechanisms of high dose (100 mg/L) and low dose (10 mg/L) CIEO and CID in inhibiting Pseudomonas aeruginosa (P. aeruginosa). In addition, we also examined the in vitro antibacterial abilities of CIEO and CID against other common pathogens including P. aeruginosa and 4 other strains. Results: Our research revealed that both high (100 mg/L) and low doses (10 mg/L) of CIEO and CID treatment significantly alleviated the reduction in locomotion behavior, lifespan, and accumulation of P. aeruginosa in C. elegans infected with the bacteria. During P. aeruginosa infection, the transcriptional expression of antimicrobial peptide-related genes (lys-1 and lys-8) in C. elegans was upregulated with low-dose CIEO and CID treatment, while this trend was suppressed at high doses. Further investigation suggested that the PMK-1 mediated p38 signaling pathway may be involved in the regulation of CIEO and CID during nematode defense against P. aeruginosa infection. Furthermore, in vitro experimental results also revealed that CIEO and CID exhibit good antibacterial effects, which may be associated with their antioxidant properties. Conclusion: Our results indicated that low-dose CIEO and CID treatment could activate the p38 signaling pathway in C. elegans, thereby regulating antimicrobial peptides, and achieving antimicrobial effects. Meanwhile, high doses of CIEO and CID might directly participate in the internal antimicrobial processes of C. elegans. Our study provides research basis for the antibacterial properties of CIEO and CID both in vivo and in vitro.

PIEZO mediates a protective mechanism for nematode Caenorhabditis elegans in response to nanoplastics caused dopaminergic neurotoxicity at environmentally relevant concentrations.

Studies have probed nanoplastic toxicity on environmental organisms, but the regulatory role of animal PIEZO-type mechanosensitive ion channel component (PIEZO) remains unclear. Herein, we identified the sole PIEZO in Caenorhabditis elegans (C. elegans), utilizing amino acid homology analysis and Trans-Membrane prediction using Hidden Markov Models (TMHMM). In C. elegans, RNAi knockdown of pezo-1 had no impact on lifespan, body length, lethality, locomotion behaviors, or oxidative response (P > 0.05). However, exposure to 15 µg/L nanopolystyrene in the pezo-1 RNAi group resulted in severe locomotion changes: head trashes (P < 0.01), body bends (P < 0.05), forward turns (P < 0.05), backward turns (P < 0.01), and impaired sensory perception, including abnormal chemotaxis to NaCl (P < 0.01) and diacetyl (P < 0.01), as well as aversive responses (P < 0.05) to nanopolystyrene compared to the wild-type group. Dopaminergic neuron damage explains these behaviors, with GST-4 (P < 0.01) and SKN-1/Nrf2 (P < 0.01) activation mitigating nanoplastic-induced damage. Our results emphasize that even at the environmentally relevant concentrations (ERC), nanoplastics can impact neurotoxicity-related endpoints, with PIEZO mediating the regulation of oxidative and antioxidative systems in response to these effects. PIEZO may be applied for assessing the neurotoxicity or oxidative stress induced by other environmental toxicants besides nanoplastics.

Exposure to epoxy-modified nanoplastics in the range of µg/L causes dysregulated intestinal permeability, reproductive capacity, and mitochondrial homeostasis by affecting antioxidant system in Caenorhabditis elegans.

Although surface chemically modified nanopolystyrene (PS) has been reported to have potential toxicity toward organisms, the impact of epoxy modification on the toxicity of PS remains largely unknown. In this study, we first investigated the prolonged exposure effects of epoxy-modified PS (PS-C2H3O) in the range of µg/L on Caenorhabditis elegans (C. elegans) including general toxicity, target organ toxicity, and organelle toxicity. Our data revealed that C. elegans exposed to PS-C2H3O led to the alterations in increased lethality (≥ 1000 µg/L), shortened body length (≥ 100 µg/L), and decreased locomotion capacity (≥ 1 µg/L). In addition, toxicity analysis on target organs and organelles indicated that exposure to PS-C2H3O enhanced intestinal permeability (≥ 100 µg/L) by inhibiting the transcriptional levels of acs-22 (encoding fatty acid transport protein) (≥ 100 µg/L) and hmp-2 (encoding α-catenin) (≥ 1000 µg/L), reduced reproductive capacity (≥ 10 µg/L), and dysregulated mitochondrial homeostasis (≥ 1 µg/L). Moreover, the activation of antioxidant enzyme system could help nematodes against the toxicity caused by PS-C2H3O exposure (≥ 10 µg/L). Furthermore, we also compared the toxicity of PS-C2H3O with other chemically modified derivatives of PS, and the toxicity order was PS-NH2 > PS-SOOOH > PS-C2H3O > PS-COOH > PS > PS-PEG. Our study highlights the potential environmental impact of PS and its derivatives on organisms and suggests that the toxicity of nanoplastics may be charge-dependent.

LncRNA KCNQ1OT1/miR-496/HMGB1 Signaling Axis Promotes Invasion and Migration of Non-small Cell Lung Cancer Cells.

Enhanced invasion and migration of non-small cell lung cancer (NSCLC) cells is the major cause of metastasis and poor prognosis in NSCLC. This study was conducted to investigate the role and mechanism of lncRNA KCNQ1OT1 in the proliferation, invasion, and migration of NSCLC cells. The expression of KCNQ1OT1 in NSCLC was analyzed in the StarBase database, and the target miRNA of KCNQ1OT1 as well as the target genes of the miRNA was predicted. Then, the mRNA expression levels of KCNQ1OT1, miR-496, and HMGB1 were detected in clinical tissue samples and cells by qRT-PCR assay. Besides, the protein levels of HMGB1 were detected by Western blot. MTT assay, transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration ability of NSCLC cells, respectively. Correlation analysis was performed to assess the correlation between the expression of KCNQ1OT1, miR-496, and HMGB1 in clinical NSCLC samples. Dual-luciferase reporter gene assay was conducted to analyze the interaction between KCNQ1OT1 and miR-496 and between miR-496 and HMGB1. The database results showed that KCNQ1OT1 was highly expressed in NSCLC. Similarly, we found that the expression level of KCNQ1OT1 was significantly higher in NSCLC tissues and cells than that in the corresponding normal tissues and cells. The results of MTT assay, transwell assay, and scratch assay demonstrated that KCNQ1OT1 significantly enhanced the proliferation, invasion, and migration of NSCLC cells. Further mechanism exploration revealed that KCNQ1OT1 could sponge miR-496, and miR-496 directly targeted and regulated the expression of HMGB1. The expression of miR-496 and either KCNQ1OT1 or HMGB1 were negatively correlated in NSCLC, while the expression of KCNQ1OT1 and HMGB1 were positively correlated. Compared with normal paracancer tissues, miR-496 was much lower and HMGB1 was much higher expressed in NSCLC tissues. The results of cotransfection also further demonstrated that miR-496 inhibitor or sh-HMGB1 cotransfected with sh-KCNQ1OT1 could significantly decrease or increase the ability of sh-KCNQ1OT1 to inhibit the proliferation, invasion, and migration of H1299 cells, respectively. In conclusion, lncRNA KCNQ1OT1 promotes the invasion and migration of NSCLC cells through miR-496/HMGB1 signaling axis.

Association between vertebrobasilar artery geometry and vertebrobasilar stenosis, recurrence, and death in posterior circulation stroke and transient ischemic attack.

BACKGROUND: Intracranial atherosclerosis is one of the primary causes of posterior circulation stroke and transient ischemic attack (TIA), particularly in people of South and East Asian heritage. Focal vessel geometry may play a role in atherosclerosis progression. Thus, we investigated the relevance of vertebrobasilar artery (VBA) geometry and vertebrobasilar atherosclerotic stenosis, recurrence, and death in posterior circulation stroke and TIA. METHODS: Four hundred and twenty patients with posterior circulation ischemic stroke or TIA were included. The VBA geometric features, comprising the geometric configurations (Tuning fork, Walking, Lambda, and No confluence), vascular bends (multi-bending and oligo-bending), and VBA stenosis degrees, were defined based on computed tomography angiography (CTA) images. Recurrence of stroke or TIA and death were assessed through a 1-year follow-up. Additionally, the relationship between VBA geometric features, VBA stenosis, and prognosis were analyzed. RESULTS: Walking type and vascular multi-bending showed significant associations with more severe VBA stenosis and distribution, and these were also more frequently observed in patients with large-artery atherosclerosis (LAA) stroke (all P < 0.05). Sixty-four patients exhibited recurrent stroke or TIA, and 31 died during the 1-year follow-up. In the binary logistic regression analysis, Walking type (P = 0.018), Lambda type (P = 0.021), and multi-bending type (P = 0.004) were found to be independently associated with stroke recurrence, while No confluence type was independently associated with death (P = 0.010). CONCLUSIONS: The geometric characteristics of the VBA are associated with vertebrobasilar stenosis, LAA stroke, 1-year recurrence, and death in posterior circulation stroke and TIA. VBA geometry may be used to stratify the risk of stroke and TIA in the posterior circulation.

LDHA and LDHB overexpression promoted the Warburg effect in malignantly transformed GES-1 cells induced by N-nitroso compounds.

N-nitroso compounds (NOCs) exposure is a major risk factor for the development of gastric cancer. However, the carcinogenic mechanisms by which NOCs induce gastric and other cancers, especially the NOCs-induced Warburg effect, have not been comprehensively studied. Lactate dehydrogenase (LDH), which has two subunits (LDHA and LDHB), plays an important role in the Warburg effect of tumor cells. Therefore, we hypothesized that LDHA and LDHB could promote Warburg effect in malignant transformed GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). GES-1 cells were exposed to 1 µmol/L MNNG and cultured for 40 passages. During the culturing process, cell proliferation, migration, and soft agar colony formation significantly increased after 30 passages. Following MNNG exposure, lactate, LDH, glucose uptake, and the expression levels of key enzymes in glycolysis were significantly increased. Knocking down LDHA or LDHB alone reduced lactate secretion, inhibited cell viability, and impaired migratory capacities. Knocking down LDHA and LDHB together fully suppressed lactate secretion and effectively suppressed the malignant phenotype of cells transformed by long-term MNNG exposure. Finally, we demonstrated that overexpression of LDHA and LDHB promotes the malignant transformation of GES-1 cells by enhancing the Warburg effect during long-term exposure to NOCs.

Potential Effect of Combined Exposure of Crystalline Silica Dust and Cigarette Smoking on the Incidence of Silicosis among Chinese Male Stone Processing Workers: A Cross-Sectional Study.

Background: Silicosis is a progressive and irreversible disease primarily caused by exposure to crystalline silica dust and, to a lesser extent, cigarette smoking. However, further research is needed to validate the potential combined effect of these risk factors on the increased incidence of the disease. Methods: A total of 1688 male workers employed at a Chinese stone processing plant between 1 January 1999 and 31 December 2019, were included in the study. Cumulative exposure to industrial crystalline silica dust and packyears of smoking were collected through health surveillance, and odds ratios (ORs) with 95% confidence intervals (CIs) for silicotic changes due to industrial silica exposure and cigarette smoking were estimated using logistic regression models. Results: Among all participants, a significant exposure-response relationship was observed between long-term exposure to industrial silica dust and radiographic findings resembling silicosis (OR 1.74, 95% CI 1.25 to 2.41). However, among middle-aged workers, a weak and statistically insignificant relationship was found between prolonged cigarette smoking and X-ray evidence of lung silicosis (OR 1.59, 95% CI 1.00 to 2.53). Furthermore, significant combined effects, exceeding the additive models, were identified in each age group and employment sector (relative risk due to interaction 0.51, 95% CI 0.08 to 3.42). Conclusions: It is critically important to implement effective dust removal measures and tobacco control strategies in order to enhance respiratory health among employees across all age groups in the stone processing industry.

SKN-1/Nrf2-dependent regulation of mitochondrial homeostasis modulates transgenerational toxicity induced by nanoplastics with different surface charges in Caenorhabditis elegans.

The toxic effects of nanoplastics on transgenerational toxicity in environmental organisms and the involved mechanisms remain poorly comprehended. This study aimed to identify the role of SKN-1/Nrf2-dependent regulation of mitochondrial homeostasis in response to transgenerational toxicity caused by changes in nanoplastic surface charges in Caenorhabditis elegans (C. elegans). Our results revealed that compared with the wild-type control and PS exposed groups, exposure to PS-NH2 or PS-SOOOH at environmentally relevant concentrations (ERC) of ≥ 1 µg/L caused transgenerational reproductive toxicity, inhibited mitochondrial unfolded protein responses (UPR) by downregulating the transcription levels of hsp-6, ubl-5, dve-1, atfs-1, haf-1, and clpp-1, membrane potential by downregulating phb-1 and phb-2, and promoted mitochondrial apoptosis by downregulating ced-4 and ced-3 and upregulating ced-9, DNA damage by upregulating hus-1, cep-1, egl-1, reactive oxygen species (ROS) by upregulating nduf-7 and nuo-6, ultimately resulting in mitochondrial homeostasis. Additionally, further study indicated that SKN-1/Nrf2 mediated antioxidant response to alleviate PS-induced toxicity in the P0 generation and dysregulated mitochondrial homeostasis to enhance PS-NH2 or PS-SOOOH-induced transgenerational toxicity. Our study highlights the momentous role of SKN-1/Nrf2 mediated mitochondrial homeostasis in the response to nanoplastics caused transgenerational toxicity in environmental organisms.

Dramatic Response to Pyrotinib and T-DM1 in HER2-Negative Metastatic Breast Cancer With 2 Activating HER2 Mutations.

HER2 signaling is activated in response to somatic HER2 mutations, which are often found in invasive lobular breast cancer (ILC) and are associated with poor prognosis. Tyrosine kinase inhibitors (TKIs) have demonstrated considerable antitumor activity in patients with HER2-mutated advanced breast cancer (BC). Further, several clinical trials have indicated that HER2-targeted antibody-drug conjugates (ADCs) exhibit promising efficacy in lung cancer with HER2 mutations, and the efficacy of ADCs against HER2-mutated BC is currently being evaluated. Several preclinical studies have demonstrated that the therapeutic efficacy of ADCs in HER2-mutated cancer can be enhanced by the addition of irreversible TKIs, but the potential of such a combined treatment regimen for the treatment of HER2-mutated BC has not been reported. Herein, we describe a case in which a patient with estrogen receptor-positive/HER2-negative metastatic ILC with 2 activating HER2 mutations (D769H and V777L) exhibited a significant and durable response to anti-HER2 treatment with pyrotinib (an irreversible TKI) in combination with ado-trastuzumab emtansine, which was administered after multiple lines of therapy that had resulted in disease progression. Further, based on the evidence from the present case, TKI plus ADC seems to be a promising combination anti-HER2 regimen for patients with HER2-negative/HER2-mutated advanced BC, although further rigorous studies are warranted to confirm these findings.

Organismal response to micro(nano)plastics at environmentally relevant concentrations: Toxicity and the underlying mechanisms.

The toxic effects of micro(nano)plastics are long-standing, flourishing and fadeless as a research topic because of its' underlying threats to the ecology and human health. Nevertheless, in most of the existing studies, some model organisms are exposed to micro(nano)plastics at a high concentration unlikely to occur in the real environment, and there is limited data available on the impact of micro(nano)plastics at environmentally relevant concentrations (ERC) on environmental organisms. To gain a better insight into micro(nano)plastic toxicity to the environmental organisms, here we integrate the related publications of micro(nano)plastic research at ERC in the past 10 years using a bibliometric analysis, and focus on the analysis of publication trends, research focuses, collaborations, and research status. In addition, we further analyze the 33 final filtered literature, and elucidate the organismal response to micro(nano)plastics at ERC from the perspective of in vivo toxic effects and mechanisms involved. This paper also puts forward some limitations of the current study and some suggestions for future research. Our study may be of great significance in further understanding the ecotoxicity of micro(nano)plastics.

Mesothelioma Due to Workplace Exposure: A Comprehensive Bibliometric Analysis of Current Situation and Future Trends.

Background: This article provides an overview of the current status and research progress of mesothelioma. Methods: A total of 2638 documents published from 1 January 2004 to 30 November 2022 were retrieved from the Web of Science Core Collection and analyzed via Microsoft Office Excel 2019, VOSviewer 1.6.18, and Tableau 2022.2. Results: There was an obvious increase in the number of publications regarding mesothelioma in the last 18 years, with the United States dominating the research field with 715 publications and 23,882 citations, while the University of Turin contributed the most (118). Occupational & Environmental Medicine was the most popular journal (80), with Corrado Magnani being the most prolific author (52) and Michele Carbone obtaining the most citations (4472). "Oncology" and "Health Science of Environment & Occupation" were the two main subjects, while the keywords "asbestos", "lung cancer", "gene expression", "apoptosis", "survival", and "cisplatin" were the most popular. Conclusions: The containment of mesothelioma calls for more participation from low- and middle-income countries, and further attention needs to be paid to clinical research.

Predictive and prognostic value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors: A systematic review and meta-analysis.

This systematic review and meta-analysis study investigates the predictive and prognostic value of PIK3CA mutations for HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs). A search of the Medline, Embase, and Cochrane Library databases yielded 17 eligible studies (1706 patients). In 10 neoadjuvant studies, the pathological complete response rate was significantly higher in wild-type PIK3CA (WT) patients than in mutated PIK3CA (MT) patients (OR = 0.45; 95% CI = 0.31-0.65; P < 0.001). In five metastasis studies, the pooled objective response rate was significantly higher in WT patients than in MT patients (OR = 0.40; 95% CI = 0.23-0.70; P = 0.001). Four metastasis studies indicated that PIK3CA mutations had a marginally significant relationship with poor progression-free survival and overall survival. Thus, PIK3CA mutations have predictive value for the treatment response of early/advanced-stage HER2-positive breast cancer treated with TKI-containing regimens.

Exposure to nanopolystyrene and its 4 chemically modified derivatives at predicted environmental concentrations causes differently regulatory mechanisms in nematode Caenorhabditis elegans.

Nanoplastics represented by nanopolystyrene (NPS) and its chemically modified derivatives are environmentally ecotoxicological hotpots in recent years, but their toxicity and underlying mechanisms have not been fully identified. Here we employed Caenorhabditis elegans as an animal model to systematically compare the toxicity between nanopolystyrene and its 4 chemically modified derivatives (PS-PEG, PS-COOH, PS-SOOOH and PS-NH2) at predicted environmental concentrations. Our study demonstrated that compared with PS exposed group, PS-NH2 exposure (15 µg/L) caused a significant decline in lifespan by suppressed DAF-16/insulin signaling and shortened body length by inhibiting DBL-1/TGF ß signaling. Different from PS-NH2 exposed group, PS-SOOOH exposure (15 µg/L) could not cause changes in lifespan, but shortened body length by inhibiting DBL-1/TGF ß signaling. In addition, PS-COOH, PS-SOOOH or PS-NH2 exposure (1 µg/L or 15 µg/L) caused more serious toxicity in reducing locomotion behavior and causing gut barrier deficit. Hence the rank order in toxicity of PS-NH2＞PS-SOOOH＞PS-COOH＞PS＞PS-PEG was identified. Furthermore, we also presented evidence to support the contention that the observed toxic effects on nematodes were linked to oxide stress and activation of anti-oxidative molecules for reversing the adverse effects induced by nanopolystyrene and its 4 chemically modified derivatives. Our data highlighted nanoplastics may be charge-dependently toxic to environmental organisms, and the screened low toxic modification may support polystyrene nanoparticles continued application for daily consumer goods and biomedicine.

Nanoplastics and Human Health: Hazard Identification and Biointerface.

Nanoplastics are associated with several risks to the ecology and toxicity to humans. Nanoplastics are synthetic polymers with dimensions ranging from 1 nm to 1 µm. They are directly released to the environment or secondarily derived from plastic disintegration in the environment. Nanoplastics are widely detected in environmental samples and the food chain; therefore, their potentially toxic effects have been widely explored. In the present review, an overview of another two potential sources of nanoplastics, exposure routes to illustrate hazard identification of nanoplastics, cell internalization, and effects on intracellular target organelles are presented. In addition, challenges on the study of nanoplastics and future research areas are summarized. This paper also summarizes some approaches to eliminate or minimize the levels of nanoplastics to ensure environmental safety and improve human health.

Cerebral vasculitis caused by Talaromyces marneffei and Aspergillus niger in a HIV-positive patient: a case report and literature review.

Cerebral vasculitis is a long-standing but flourishing and fadeless research topic. Infections are a frequent cause of cerebral vasculitis, vital to diagnose due to involvement of specific anti-infection treatments. A 65-year-old man visited the hospital for his neurological symptoms without obvious inducements. After admission, radiological examination and comprehensive conventional microbiological tests (CMTs) revealed suspected intracranial infectious vasculitis. Metagenomic next-generation sequencing (mNGS) and reverse transcription-polymerase chain reaction further confirmed that his cerebral vasculitis was caused by Talaromyces marneffei (T. marneffei) and Aspergillus niger (A. niger) co-infection. The patient's final diagnosis changed from initial herpetic encephalitis, due to the past history of cephalosome and facial herpes and non-significant antiviral therapeutic effects, to fungal cerebral vasculitis. The patient was discharged after use of targeted antifungal therapies on day 18 of his admission, and his associated symptoms disappeared completely at follow-up 3 weeks later. We first illustrated the presence of uncommon cerebral vasculitis caused by T. marneffei and A. niger in a human immunodeficiency virus-positive patient. In clinically suspected patients with infectious cerebral vasculitis, mNGS should be performed to detect potential pathogens if CMTs may not provide useful pathogenic clues, highlighting the importance of mNGS in the diagnosis and treatment of infectious diseases.

Reproductive toxicity and underlying mechanisms of di(2-ethylhexyl) phthalate in nematode Caenorhabditis elegans.

DEHP (di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability (0.1, 1 and 10 mg/L), and egg-laying rate (1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus (1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration-dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration (10 mg/L) DEHP can inhibit the expression of autophagy genes (atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations (0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.

Response of tyramine and glutamate related signals to nanoplastic exposure in Caenorhabditis elegans.

Neurotransmission related signals are involved in the control of response to toxicants. We here focused on the tyramine and the glutamate related signals to determine their roles in regulating nanoplastic toxicity in Caenorhabditis elegans. In the range of µg/L, exposure to nanopolystyrene (100 nm) increased the expression of tdc-1 encoding a tyrosine decarboxylase required for synthesis of tyramine, and decreased the expression of eat-4 encoding a glutamate transporter. Both TDC-1 and EAT-4 could act in the neurons to regulate the nanopolystyrene toxicity. Meanwhile, neuronal RNAi knockdown of tdc-1 induced a susceptibility to nanopolystyrene toxicity, and neuronal RNAi knockdown of eat-4 induced a resistance to nanopolystyrene toxicity. In the neurons, TYRA-2 functioned as the corresponding receptor of tyramine and acted upstream of MPK-1 signaling to regulate the nanopolystyrene toxicity. Moreover, during the control of nanopolystyrene toxicity, GLR-4 and GLR-8 were identified as the corresponding glutamate receptors, and acted upstream of JNK-1 signaling and DBL-1 signaling, respectively. Our results demonstrated the crucial roles of tyramine and glutamate related signals in regulating the toxicity of nanoplastics in organisms.