Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors. METHODS: We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM. RESULTS: We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis. CONCLUSIONS: Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

MPC-n (IgG) improves long-term cognitive impairment in the mouse model of repetitive mild traumatic brain injury.

BACKGROUND: Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. METHODS: We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. RESULTS: Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. CONCLUSIONS: In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.

Phosphogypsum/titanium gypsum coupling for enhanced biochar immobilization of lead: Mineralization reaction behavior and electron transfer effect.

The hazards caused by Pb pollution have received worldwide attention. Phosphogypsum (PG) and titanium gypsum (TG) have the disadvantage of limited adsorption capacity and poor dispersion when used as heavy metal adsorbents on their own. The excellent pore and electron transfer capacity of biochar makes it possible to combine with PG and TG to solidify/stabilize Pb2+. In this study, the mechanism of Pb2+ adsorption/immobilization by rice husk biochar (BC) combined with PG/TG was investigated in terms of both mineral formation and electron transfer rate. The removal rate of Pb2+ by BC composite PG (BC/PG-Pb) or TG (BC/TG-Pb) was as high as 97%-98%, an increase of 120.9% and 122.5% over BC. Adsorption kinetics and mineral precipitation results indicate that the main removal of Pb2+ from BC/PG-Pb and BC/TG-Pb is achieved by PG/TG induced Pb-sulfate and Pb-phosphate formation. The addition of PG/TG significantly enhances the formation of stable Pb-minerals on the biochar surface, with the proportion of non-bioaccessible forms exceeding 50%. The four-step extraction results confirm that P and F in PG/TG are key in facilitating the conversion of Pb minerals to pyromorphite. The rich pore structure of biochar not only disperses the easily agglomerated PG/TG onto the biochar surface, but also attracts Pb2+ for uniformly dispersed precipitation. Furthermore, the excellent electrical conductivity and smooth electron transfer channels of biochar facilitate the reaction rate of Pb2+ mineralization. Overall, the use of biochar in combination with PG/TG is a promising technology for the combination of solid waste resourceisation and Pb remediation.

Interactions effects of nano-microplastics and heavy metals in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).

The interaction between microplastics and contaminants has potentially generated new undefined risks on animals and ecosystems, and nano-microplastics are considered to be more harmful than microplastics. This experiment investigated the interactions and effects of nano-microplastics with heavy metals cadmium in hybrid snakehead. Different concentrations of nano-microplastics 80 nm (50 µg/L and 500 µg/L) and Cd (50 µg/L) were used for exposure, and four sampling points were set for 24 h, 48 h, 96 h and clear-48 h. Results indicated that the morphology of gill was altered under the influence of nano-microplastics and cadmium, and the damage was aggravated with time. Nano-microplastics and Cd can cause oxidative damage to fish liver partly by effect the activities of antioxidant enzyme, and significantly suppressed the expressions of genes related to the inflammation (IL-1ß and TNF-α) and as well as significantly up-regulated the expression of genes HSP70 and SOD. Additionally, the mRNA levels of MT gene can be speculated that the heavy metal cadmium may accumulated in the body over time. And the concentration of heavy metals will also affect their accumulation in the body. Our study elucidated the nano-microplastics and Cd will increase the impact on environmental and organisms that the nano-microplastics contribute to the bioaccumulation of metals, which served as a new support for study the interaction between environmental contaminants.

Antibiotic resistance bacteria and antibiotic resistance genes survived from the extremely acidity posing a risk on intestinal bacteria in an in vitro digestion model by horizontal gene transfer.

Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants posing risk to human health. To investigate the pathogenic ARBs and the horizontal gene transfer (HGT) via both extracellular ARGs (eARGs) and intracellular ARGs (iARGs), an in vitro digestion simulation system was established to monitoring the ARB and ARGs passing through the artificial digestive tract. The results showed that ARB was mostly affected by the acidity of the gastric fluid with about 99% ARB (total population of 2.45 × 109-2.54 × 109) killed at pH 2.0 and severe damage of bacterial cell membrane. However, more than 80% ARB (total population of 2.71 × 109-3.90 × 109) survived the challenge when the pH of the gastric fluid was 3.0 and above. Most ARB died from the high acidity, but its ARGs, intI1 and 16 S rRNA could be detected. The eARGs (accounting for 0.03-24.56% of total genes) were less than iARGs obviously. The eARGs showed greater HGT potential than that of iARGs, suggesting that transformation occurred more easily than conjugation. The transferring potential followed: tet (100%) > sul (75%) > bla (58%), related to the high correlation of intI1 with tetA and sul2 (p < 0.01). Moreover, gastric juice of pH 1.0 could decrease the transfer frequency of ARGs by 2-3 order of magnitude compared to the control, but still posing potential risks to human health. Under the treatment of digestive fluid, ARGs showed high gene horizontal transfer potential, suggesting that food-borne ARBs pose a great risk of horizontal transfer of ARGs to intestinal bacteria.

The role of extracellular vesicles in traumatic brain injury-induced acute lung injury.

Acute lung injury (ALI), a common complication after traumatic brain injury (TBI), can evolve into acute respiratory distress syndrome (ARDS) and has a mortality rate of 30%-40%. Secondary ALI after TBI exhibits the following typical pathological features: infiltration of neutrophils into the alveolar and interstitial space, alveolar septal thickening, alveolar edema, and hemorrhage. Extracellular vesicles (EVs) were recently identified as key mediators in TBI-induced ALI. Due to their small size and lipid bilayer, they can pass through the disrupted blood-brain barrier (BBB) into the peripheral circulation and deliver their contents, such as genetic material and proteins, to target cells through processes such as fusion, receptor-mediated interactions, and uptake. Acting as messengers, EVs contribute to mediating brain-lung cross talk after TBI. In this review, we aim to summarize the mechanism of EVs in TBI-induced ALI, which may provide new ideas for clinical treatment.

Precise Control of Customized Macrophage Cell Robot for Targeted Therapy of Solid Tumors with Minimal Invasion.

Injecting micro/nanorobots into the body to kill tumors is one of the ultimate ambitions for medical nanotechnology. However, injecting current micro/nanorobots based on 3D-printed biocompatible materials directly into blood vessels for targeted therapy is often difficult, and mistakes in targeting can cause serious side effects, such as blood clots, oxidative stress, or inflammation. The natural affinity of macrophages to tumors, and their natural phagocytosis and ability to invade tumors, make them outstanding drug delivery vehicles for targeted tumor therapy. Hence, a magnetically controlled cell robot (MCR) based on a macrophage drug carrier is proposed. Here, living macrophages are converted into MCRs through endocytosis of specially-designed magnetic nanoparticles loaded with doxorubicin and indocyanine green. Following this, the MCRs can be transported to tumors through the blood vessels using external magnetic fields, and penetrate the blood vessels into the interior of the tumor due to their deformability. With the MCR's cascaded drug release, targeted killing of tumors in mice is demonstrated, with minimal effects on the normal surrounding tissue. The ability to impart precise drug doses onto natural cells, such as macrophages, and load various functional components into the MCRs, offers an efficient method for precise targeted therapy.

Effects of mixed antimicrobial peptide on the growth performance, antioxidant and immune responses and disease resistance of Pengze crucian carp (Carassius auratus var. Pengze).

Antimicrobial peptides have broad-spectrum antibacterial properties and low drug resistance, and they demonstrate great potential as antibiotic substitutes. In this study, five dietary mixed antimicrobial peptide supplement groups were set and fed to Pengze crucian carp for 10 weeks. The 6 groups were G0 (control group) and 5 additional groups: G1 (100 mg/kg), G2 (200 mg/kg), G3 (400 mg/kg), G4 (800 mg/kg) and G5 (1600 mg/kg). The results showed that the final body weight (FBW), weight gain rate (WGR) and specific growth rate (SGR) of fish in G1 and G2 were higher than those of fish in the control group, and G1 was significantly higher than G0 (P < 0.05). In addition, the FBW, WGR, and SGR of the G3 group were significantly lower than those of the G0 group. The chymotrypsin, lipase and amylase activities of G1 and G2 were significantly upregulated compared with G0 and reached peak values in G1. The activity of T-AOC and SOD in the addition group was higher (except G2 and G4) than that in the control groups, and significantly increased in G3 compared to the control group. The activity of MDA in the addition group was lower than that in the control group (p > 0.05). The expression levels of TLR-4, MYD88 and TNF-α in the three organs of the addition group were higher than those in G0 and reached the peak value in G3 (p < 0.05). Furthermore, the expression levels of TLR-4, MYD88 and TNF-α in the three organs of G3 were significantly lower than those in G0 and lower than those in the other supplemented groups. The expression levels of IL-10 and IL-11 tended to be upregulated after A. hydrophila challenge, and G3 in different organs was significantly higher than that in other supplemented groups and G0. The results of this study show that an appropriate amount of mixed antimicrobial peptides can improve the growth performance and antioxidant and immune capabilities of Pengze crucian carp and can also play a positive role in the treatment of A. hydrophila infection.

A dosage-effect assessment of acute toxicology tests of microplastic exposure in filter-feeding fish.

Abundant microplastics was found in aquatic ecosystem and aquatic organisms, which raised many concerns in public. Silver carp (Hypophthalmichthys molitrix), a species filter-feeding planktivorous fish, feed on particle between 4 and 85 µm in size, and the respiratory process works together with feeding mechanism when filtering plankton from water. The aim of this study was to assess the physiological response of silver carp exposed to 5 µm polystyrene microspheres during 48 h of exposure followed by 48 h of depuration through the gill histology, and oxidative stress biomarkers in intestine. The results revealed that microplastics can pass through the whole digestive tract of silver carp and be excreted by feces. Low microplastic concentration (80 µg/L) induced oxidative stress and up-regulation of TUB84 and HSP70 gene in intestine, and silver carp have ability to recover after the exposure to microplastic was removed. High microplastic concentration (800 µg/L) definitely cause significant damage to gills and intestines, in this situation, far beyond the possibility of fish own repair, and even when the threaten removed, silver carp can't recovery soon. Our studies assessed the dosage-effect relationship with physiological stress on silver carp when exposure to microplastics.

Characterization and spatial distribution of microplastics in two wild captured economic freshwater fish from north and west rivers of Guangdong province.

As a new type of pollutant, microplastics are of emerging widespread concern, while amount of research done in freshwater environments and organisms is litter compared to that in marine. Following this reality, the categories of MPs in two economic freshwater fish at 25 sites from 11 cities in the north and west rivers of Guangdong province were documented. Here, 76 individuals belong Oreochromis niloticus and Cirrhinus molitorella were investigated and microplastics were found in the GITs of 43.4% and gills of 25%. The average abundances of microplastics have significant difference between Oreochromis niloticus (0.015 items/ g) and Cirrhinus molitorella (0.031 items/g), while no difference by individual (~1.9 items). The plastics were dominated by white in color (61%), fragment in shape (67%), and lass than 1 mm in size (74%). The spatial distribution of microplastics revealed that there are significant differences between different cities in average abundances, and the highest average abundances of MPs were found in Zhanjiang city (4.25 items/individual) and Guangzhou city (0.044 items/g), respectively. Our results fully proved that the microplastics was widely ingested by wild fish species and suggested that the abundance and distribution of microplastics are positively related with the development of economy, tourism, industry, agriculture, and fishery.

Paroxetine suppresses reactive microglia-mediated but not lipopolysaccharide-induced inflammatory responses in primary astrocytes.

BACKGROUND: Astrocytes are the most abundant glial cells in a brain that mediate inflammatory responses and provide trophic support for neurons. We have previously disclosed that paroxetine, a common selective serotonin reuptake inhibitor, ameliorates LPS-induced microglia activation. However, it remains elusive for the role of paroxetine in astrocytic responses. METHODS: Isolated primary astrocytes were pretreated with paroxetine and stimulated with different stimuli, lipopolysaccharide (LPS) or microglia conditioned medium pre-activated with LPS (M/Lps). Inflammatory and neurotrophic responses, underlying mechanisms and the impact on neuronal survival were assessed. RESULTS: Paroxetine had no impact on LPS-stimulated iNOS, TNF-α, and IL-1ß expression, but inhibited M/Lps-induced TNF-α and IL-1ß expression in primary astrocytes. Paroxetine suppressed M/Lps- but not LPS-induced activation of NF-κB and had no impact on the activation of MAPKs and STAT3. Incubation with the resulted astrocyte conditioned media caused no change in the viability of SH-SY5Y cells. BDNF and MANF mRNA expressions were upregulated by M/Lps and paroxetine, respectively. However, M/Lps- or LPS-induced extracellular releases of NO, TNF-α, and/or BDNF in astrocytes were in minor amount compared to those by microglia. CONCLUSIONS: Paroxetine ameliorates the reactive microglia-mediated inflammatory responses in astrocytes partially via inhibition of the NF-κB pathway but has no impact on LPS-stimulated astrocyte activation. While the effects of paroxetine on secondary astrocytic responses are not robust compared to its effect on the innate immune responses of microglia, the results together may implicate a therapeutic potential of paroxetine against neuroinflammation-associated neurological disorders such as Parkinson's disease.

Expression of HSP70 family mRNAs in albino northern snakehead, Channa argus: Response to extreme temperature stress and bacterial infection.

The wild albino northern snakehead, Channa argus, has only been found in Jialing Rivers System of China so far. It is easy to be affected by the environmental factors such as temperature changes and bacterial infection, thus causing a huge economic loss. Therefore, this study cloned a 2,213 bp cDNA that encodes a protein of heat shock protein 70 (CaHSP70), which has an open reading frame (ORF) that encodes 639 amino acids and the corresponding polypeptides of 70.50 kDa. And the oretical isoelectric point (pI) of CaHSP70 is 5.79. Additionally, we also cloned a cDNA for heat shock cognate protein 70 (CaHSC70) with a total length of 2,300 bp. And the ORF of CaHSC70 encodes 648 amino acids and 71.18 kDa peptides. The pI of CaHSC70 is 5.22. Moreover, the cDNA length of stress-70 protein mitochondrial (CaHSPA9) is 2,944 bp with an ORF that encodes 679 amino acids, polypeptides of 73.74 kDa, and a pI of 6.68. The quantitative real-time PCR (qRT-PCR) analysis showed that the mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9 genes were tissue-specific in the control groups. After the heat shock at 37 °C, the mRNA expression levels of CaHSP70 were extremely significantly upregulated in the kidney, liver, spleen, and brain tissues, while fewer mRNA expression levels of CaHSC70 and CaHSPA9 showed a relatively induction in these tissues. In contrast, after the cold shock at 8.5 °C, fewer mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9 showed the changes of expression in all the tissues, compared to heat shock. In addition, CaHSP70, CaHSC70, and CaHSPA9 mRNA expression levels showed an overall trend of first upregulating and then falling after Edwardsiella tarda (strain No. DL1,476) challenge. In conclusion, this study demonstrated that temperature had a great effect on the mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9, and the mRNA expression levels of these three genes were also sensitive to pathogen infection, especially CaHSP70 in the albino C. argus.

Efficient removal of triclosan via peroxymonosulfate activated by a ppb level dosage of Co(II) in water: Reaction kinetics, mechanisms and detoxification.

Triclosan (TCS), an extensively used broad-spectrum antimicrobial agent, has raised significant environmental concerns regarding its widespread occurrence in waters. In this study, the removal of TCS in aqueous solution via peroxymonosulfate (PMS) activated by an extremely low-level Co2+ (0.02 µM) was systematically investigated. During preliminary test, TCS (10 µM) was totally degraded in 30 min by using 0.1 µM Co2+ and 40 µM PMS at pH 7.0 with a degradation rate constant of 0.1219 min-1. A first-order apparent degradation rate of TCS was found with respect to the PMS concentrations. At extremely low dosage of Co2+ (0.02 µM), the presence of NO3-, HCO3-, PLFA, and SRHA within test concentrations significantly inhibited TCS removal, while a dual effect of Cl- on the degradation rate of TCS was observed. The quenching experiments verified that SO4- was the dominant reactive oxygen species (ROS) rather than OH. Six major intermediates were identified using TOF-LC-MS, based on which we proposed three associated reaction pathways including hydroxylation, ether bond breakage, and dechlorination. Toxicity predictions by ECOSAR software exhibited aquatic toxicity reduction of TCS after Co2+/PMS treatment. We outlook these findings to advance the feasibility of organic contaminants removal via Co2+/PMS system with Co2+ at extremely low levels.

Transverse microvibrations-based guide wires drag reduction evaluation for endovascular interventional application.

When conducting endovascular interventional surgery, doctors usually experience high viscous resistance resulting from direct contact with blood when operating the guide wire in blood vessels, which reduces the operational efficiency. Improper operation can cause vascular injuries and greatly reduce surgical safety, sometimes leading to the death of the patient. This paper presents a new method that applies transverse microvibrations at the proximal end of a conventional passive guide wire to reduce viscous resistance. The effect of the proposed method in reducing the viscous resistance in the fluid is studied. The influences of the tube diameter, medium density, and applied vibration frequency on the viscous force are investigated. Finally, for endovascular therapy, a mathematical model of the viscous force of the guide wire based on the proposed method is established in the environment of human blood vessels to predict the magnitude of the viscous force exerted on the guide wire and analyze the drag reduction effect of the proposed method. The effectiveness of the proposed method in drag reduction and its feasibility in improving surgical safety are experimentally demonstrated. The experimental results indicate that the proposed method can assist the doctor during complicated and variable operation conditions.

[The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture ( EA) on the related protein expression of the signaling pathway of the toll-like receptor2 (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Fifty male SD rats were randomly divided into 5 groups: normal group, SMD group, AGA model group, medication group and EA group, 10 rats in each group. SMD group established model by inducing SMD, other groups established AGA model by inducing monosodium urate, except the normal group. Two days before model was established, normal and SMD and AGA model groups were lavaged with normal saline (20 mL/kg), medication group was lavaged with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once daily, continuously for 9 days. Then the join sewlling index was observed periodically, the protein expression of TLR2 and MYD88 was determined by immunohistochemistry. RESULTS: Compared to the normal group, the join sewlling of the SMD group in test join increased significantly (P<0. 05) and the protein expression of TLR2 and MYD88 in synovial tissue has not statistically significant (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial tissue of model group increased significantly P<0. 05); The medication and EA group compared to the model group, the protein expression of TLR2 and MYD88 in synovial tissue decreased significantly (P <0. 05), the join sewlling in test join decreased significantly P<1. 05); There were not statistically significant between the EA group and the medication group (P>0.05). CONCLUSION: EA can alleviate the symptoms of AGA, which may be related to regulation of the protein expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

The effects of nanoplastics and microcystin-LR coexposure on Aristichthys nobilis at the early developmental stages.

Nanoplastics (NPs) and microcystin-LR (MC-LR) are two common and harmful pollutants in water environments, especially at aquafarm where are full of plastic products and algae. It is of great significance to study the toxic effects and mechanisms of the NPs and/or MC-LR on fish at the early stage. In this study, the embryo and larvae of a filtering-feeding fish, Aristichthys nobilis, were used as the research objects. The results showed that the survival and hatching rates of the embryo were not significantly affected by the environmental concentration exposure of these two pollutants. Scanning electron microscopy (SEM) observation displayed that NPs adhered to the surface of the embryo membrane. Transcriptomic and bioinformatic analyses revealed that the NPs exposure activated neuromuscular junction development and skeletal muscle fiber in larvae, and affected C5-Branched dibasic acid metabolism. The metabolic and biosynthetic processes of zeaxanthin, xanthophyll, tetraterpenoid, and carotenoid were suppressed after the MC-LR exposure, which was harmful to the retinol metabolism of fish. Excessive production of superoxide dismutase (SOD) was detected under the MC-LR exposure. The MC-LR and NPs coexposure triggered primary immunodeficiency and adaptive immune response, leading to the possibility of reduced fitness of A.nobilis during the development. Collectively, our results indicate that environmental concentration NPs and MC-LR coexposure could cause toxic damage and enhance sick risk in A.nobilis, providing new insights into the risk of NPs and MC-LR on filtering-feeding fish.

Plasma von Willebrand factor levels in patients with cancer: A meta­analysis.

von Willebrand Factor (VWF) is well recognized for being dysregulated in various malignancies and has emerged as a potential biomarker for cancer detection. The present meta-analysis aimed to elucidate the association between plasma VWF and the incidence and metastasis of cancer. For this purpose, a comprehensive search was conducted across multiple databases from their inception until March 3, 2023. This culminated in the selection of 15 original studies on various types of cancer, including a collective sample of 1,403 individuals. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed as statistical parameters to determine the association between plasma VWF and the incidence and metastasis of cancer. These were estimated using a random-effects model. The pooled data revealed that the plasma VWF levels of patients with cancer were significantly elevated compared with those of healthy controls (SMD, 0.98; 95% CI, 0.59-1.36), and a significant association was observed between plasma VWF levels and cancer metastasis (SMD, 0.69; 95% CI, 0.33-1.06). The symmetry of the Begg's funnel plots indicated that no significant bias was present in the analyses of VWF in cancer and its metastasis. In summary, the results of the present meta-analysis support the hypothesis that increased plasma VWF levels may serve as a biomarker for cancer and metastatic progression.

Toxic effects of nanoplastics and microcystin-LR coexposure on the liver-gut axis of Hypophthalmichthys molitrix.

Plastic products and nutrients are widely used in aquaculture facilities, resulting in copresence of nanoplastics (NPs) released from plastics and microcystins (MCs) from toxic cyanobacteria. The potential effects of NPs-MCs coexposure on aquatic products require investigation. This study investigated the toxic effects of polystyrene (PS) NPs and MC-LR on the gut-liver axis of silver carp Hypophthalmichthys molitrix, a representative commercial fish, and explored the effects of the coexposure on intestinal microorganism structure and liver metabolic function using traditional toxicology and multi-omics association analysis. The results showed that the PS-NPs and MC-LR coexposure significantly shortened villi length, and the higher the concentration of PS-NPs, the more obvious the villi shortening. The coexposure of high concentrations of PS-NPs and MC-LR increased the hepatocyte space in fish, and caused obvious loss of gill filaments. The diversity and richness of the fish gut microbes significantly increased after the PS-NPs exposure, and this trend was amplified in the copresence of MC-LR. In the coexposure, MC-LR contributed more to the alteration of fish liver metabolism, which affected the enrichment pathway in glycerophospholipid metabolism and folic acid biosynthesis, and there was a correlation between the differential glycerophospholipid metabolites and affected bacteria. These results suggested that the toxic mechanism of PS-NPs and MC-LR coexposure may be pathological changes of the liver, gut, and gill tissues, intestinal microbiota disturbance, and glycerophospholipid metabolism imbalance. The findings not only improve the understanding of environmental risks of NPs combined with other pollutants, but also provide potential microbiota and glycerophospholipid biomarkers in silver carp.

In vitro assessment of the bacterial stress response and resistance evolution during multidrug-resistant bacterial invasion of the Xenopus tropicalis intestinal tract under typical stresses.

The intestinal microbiome might be both a sink and source of resistance genes (RGs). To investigate the impact of environmental stress on the disturbance of exogenous multidrug-resistant bacteria (mARB) within the indigenous microbiome and proliferation of RGs, an intestinal conjugative system was established to simulate the invasion of mARB into the intestinal microbiota in vitro. Oxytetracycline (OTC) and heavy metals (Zn, Cu, Pb), commonly encountered in aquaculture, were selected as typical stresses for investigation. Adenosine 5'-triphosphate (ATP), hydroxyl radical (OH·-) and extracellular polymeric substance (EPS) were measured to investigate their influence on the acceptance of RGs by intestinal bacteria. The results showed that the transfer and diffusion of RGs under typical combined stressors were greater than those under a single stressor. Combined effect of OTC and heavy metals (Zn, Cu) significantly increased the activity and extracellular EPS content of bacteria in the intestinal conjugative system, increasing intI3 and RG abundance. OTC induced a notable inhibitory response in Citrobacter and exerted the proportion of Citrobacter and Carnobacterium in microbiota. The introduction of stressors stimulates the proliferation and dissemination of RGs within the intestinal environment. These results enhance our comprehension of the typical stresses effect on the RGs dispersal in the intestine.

Triclosan-loaded aged microplastics exacerbate oxidative stress and neurotoxicity in Xenopus tropicalis tadpoles via increased bioaccumulation.

Microplastics and chlorine-containing triclosan (TCS) are widespread in aquatic environments and may pose health risks to organisms. However, studies on the combined toxicity of aged microplastics and TCS are limited. To investigate the toxic effects and potential mechanisms associated with co-exposure to TCS adsorbed on aged polyethylene microplastics (aPE-MPs) at environmentally relevant concentrations, a 7-day chronic exposure experiment was conducted using Xenopus tropicalis tadpoles. The results showed that the overall particle size of aPE-MPs decreased after 30 days of UV aging, whereas the increase in specific surface area improved the adsorption capacity of aPE-MPs for TCS, resulting in the bioaccumulation of TCS under dual-exposure conditions in the order of aPE-TCS > PE-TCS > TCS. Co-exposure to aPE-MPs and TCS exacerbated oxidative stress and neurotoxicity to a greater extent than a single exposure. Significant upregulation of pro-symptomatic factors (IL-ß and IL-6) and antioxidant enzyme activities (SOD and CAT) indicated that the aPE-TCS combination caused more severe oxidative stress and inflammation. Molecular docking revealed the molecular mechanism of the direct interaction between TCS and SOD, CAT, and AChE proteins, which explains why aPE-MPs promote the bioaccumulation of TCS, causing increased toxicity upon combined exposure. These results emphasize the need to be aware of the combined toxicity caused by the increased ability of aged microplastics to carry contaminants.