Zwitterionic Biomaterials.

The term "zwitterionic polymers" refers to polymers that bear a pair of oppositely charged groups in their repeating units. When these oppositely charged groups are equally distributed at the molecular level, the molecules exhibit an overall neutral charge with a strong hydration effect via ionic solvation. The strong hydration effect constitutes the foundation of a series of exceptional properties of zwitterionic materials, including resistance to protein adsorption, lubrication at interfaces, promotion of protein stabilities, antifreezing in solutions, etc. As a result, zwitterionic materials have drawn great attention in biomedical and engineering applications in recent years. In this review, we give a comprehensive and panoramic overview of zwitterionic materials, covering the fundamentals of hydration and nonfouling behaviors, different types of zwitterionic surfaces and polymers, and their biomedical applications.

Mitochondria: An Emerging Unavoidable Link in the Pathogenesis of Periodontitis Caused by Porphyromonas gingivalis.

Porphyromonas gingivalis (P. gingivalis) is a key pathogen of periodontitis. Increasing evidence shows that P. gingivalis signals to mitochondria in periodontal cells, including gingival epithelial cells, gingival fibroblast cells, immune cells, etc. Mitochondrial dysfunction affects the cellular state and participates in periodontal inflammatory response through the aberrant release of mitochondrial contents. In the current review, it was summarized that P. gingivalis induced mitochondrial dysfunction by altering the mitochondrial metabolic state, unbalancing mitochondrial quality control, prompting mitochondrial reactive oxygen species (ROS) production, and regulating mitochondria-mediated apoptosis. This review outlines the impacts of P. gingivalis and its virulence factors on the mitochondrial function of periodontal cells and their role in periodontitis.

Polystyrene nanoplastics aggravates lipopolysaccharide-induced apoptosis in mouse kidney cells by regulating IRE1/XBP1 endoplasmic reticulum stress pathway via oxidative stress.

Nanoplastics (NPs) pollution poses a huge threat to the ecosystem and has become one of the environmental pollutants that have attracted much attention. There is increasing evidence that both oxidative stress and endoplasmic reticulum stress (ERS) are associated with polystyrene nanoplastics (PS-NPs) exposure. Lipopolysaccharide (LPS) has been shown to induce apoptotic damage in various tissues, but whether PS-NPs can aggravate LPS-induced apoptosis in mouse kidneys through oxidative stress-regulated inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) ERS pathway remains unclear. In this study, based on the establishment of in vitro and in vivo PS-NPs and LPS exposure models alone and in combination in mice and HEK293 cells, the effects and mechanisms of PS-NPs on LPS-induced renal cell apoptosis were investigated. The results showed that PS-NPs could aggravate LPS-induced apoptosis. PS-NPs/LPS can induce ERS through oxidative stress, activate the IRE1/XBP1 pathway, and promote the expression of apoptosis markers (Caspase-3 and Caspase-12). Kidney oxidative stress, ERS, and apoptosis in PS-NPs + LPS combined exposure group were more severe than those in the single exposure group. Interestingly, 4-phenylbutyric acid-treated HEK293 cells inhibited the expression of the IRE1/XBP1 ERS pathway and apoptotic factors in the PS-NPs + LPS combined exposure group. N-acetyl-L-cysteine effectively blocked the activation of the IRE1/XBP1 ERS pathway, suggesting that PS-NPs-induced oxidative stress is an early event that triggers ERS. Collectively, these results confirmed that PS-NPs aggravated LPS-induced apoptosis through the oxidative stress-induced IRE1/XBP1 ERS pathway. Our study provides new insights into the health threats of PS-NPs exposed to mammals and humans.

Polystyrene nanoplastics exacerbated lipopolysaccharide-induced necroptosis and inflammation via the ROS/MAPK pathway in mice spleen.

Plastics are novel environmental pollutants with potential threats to the ecosystem. At least 5.25 trillion plastic particles in the environment, of which nanoplastics are <100 nm in diameter. Polystyrene nanoplastics (PS-NPs) exposure damaged the spleen's immune function. Lipopolysaccharide (LPS) induced other toxicants to damage cells and organs, triggering inflammation. However, the mechanism of PS-NPs aggravated LPS-induced spleen injury remains unclear. In this study, the PS-NPs or/and LPS mice exposure model was replicated by intraperitoneal injection of PS-NPs or/and LPS, and PS-NPs or/and LPS were exposed to RAW264.7 cells. The histopathological and ultrastructural changes of the mice spleen were observed by H&E staining and transmission electron microscope. Western Blot, qRT-PCR, and fluorescent probes staining were used to detect reactive oxygen species (ROS), oxidative stress indicators, inflammatory factors, and necroptosis-related indicators in mice spleen and RAW264.7 cells. The results showed that PS-NPs or LPS induced oxidative stress, activated the MAPK pathway, and eventually caused necroptosis and inflammation in mice spleen and RAW264.7 cells. Compared with the single treatment group, the changes in PS-NPs + LPS group were more obvious. Furthermore, ROS inhibitor N-Acetyl-L-cysteine (NAC) significantly inhibited the activation of the mitogen-activated protein kinase (MAPK) signaling pathway caused by co-treatment of PS-NPs and LPS, reducing necroptosis and inflammation. The results demonstrated that PS-NPs promoted LPS-induced spleen necroptosis and inflammation in mice through the ROS/MAPK pathway. This study increases the data on the damage of PS-NPs to the organism and expands the research ideas and clues.

Clinical efficacy of melatonin as adjunctive therapy to non-surgical treatment of periodontitis: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of adjunctive melatonin supplementation on clinical outcomes after non-surgical periodontal treatment. METHODS: PubMed, Embase, and Web of Science databases were systematically searched for randomised controlled trials (RCTs) of melatonin adjuvant therapy for periodontitis from inception until May 2021. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021250630). The risk of bias of included studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. The pooled effect estimates were calculated by a random-effects model, and results were expressed as weighted mean differences (WMD). RESULTS: Seven RCTs comprising 412 participants were included in the meta-analysis. The pooled results showed that adjuvant use of melatonin for non-surgical periodontal treatment significantly improved the probing depth (PD) [WMD = - 1.18, 95% CI (- 1.75, - 0.62) I2 = 85.7%], clinical attachment loss (CAL) [WMD = - 1.16, 95% CI (- 1.60, - 0.72) I2 = 76.7%] and gingival index (WMD = - 0.29, 95%CI [- 0.48, - 0.11], I2 = 63.6%) compared with non-surgical treatment alone. In addition, subgroup analysis showed that higher doses of melatonin (3-10 mg) significantly improved PD [WMD = - 1.32, 95%CI (- 2.31, - 0.15) I2 = 93%] and CAL [WMD = - 1.30, 95%CI (- 1.80, - 0.81) I2 = 73.7%] compared with lower doses of melatonin (< 3 mg). CONCLUSIONS: We found that adjunctive melatonin supplementation can significantly improve the periodontal status after non-surgical treatment, suggesting that melatonin may be a new adjuvant therapy for periodontitis when non-surgical periodontal treatment alone cannot achieve the desired improvement.

Preparation of bioactive glass nanoparticles with highly and evenly doped calcium ions by reactive flash nanoprecipitation.

Nanoscale bioactive glass particles have greater bioactivity than microscale bioactive glass particles, due to their high-specific surface area and fast ion release rate in body fluid. However, preparation of bioactive glass nanoparticles (BGNPs) is difficult since calcium is not easy to be highly doped into the forming silica atom network, leading to an uneven distribution and a low content of calcium. In addition, BGNPs are usually prepared in a dilute solution to avoid agglomeration of the nanoparticles, which decreases the production efficiency and increases the cost. In this work, BGNPs are prepared by a method of the reactive flash nanoprecipitation (RFNP) as well as a traditional sol-gel method. The results indicate that the BGNPs by the RFNP present a smaller size, narrower size distribution, more uniform composition, and better bioactivity than those by the traditional sol-gel method. The obtained BGNPs have uniform compositions close to the feed values. The high and even doping of calcium in the BGNPs is achieved. This successful doping of calcium into nanoparticles by the RFNP demonstrates a promising way to effectively generate high-quality BGNPs for bone repairs.

Exploring the toxicity of the aged styrene-butadiene rubber microplastics to petroleum hydrocarbon-degrading bacteria under compound pollution system.

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

[Research Progress in Biomimetic Synthesis of Nano-Hydroxyapatite in Bone Tissue Engineering].

Nano hydroxyapatite (nHAp), a main component of the inorganic composition of human bones and teeth, is widely used in bone tissue engineering, bone defect repair and replacement, for example, for its biocompatibility, bioactivity, bioaffinity and the ability to induce bone regeneration. Nano hydroxyapatite contains calcium and phosphorus, elements that can be replaced through the normal metabolic channels of the human body. Therefore, after implantation, it can be partially or completely absorbed and replaced by human tissues and can effectively assist bone regeneration, which makes it an ideal material for bone repair. However, traditional nHAp material is brittle and hard to be degraded in human body. In addition, nHAp has poor stability due to its high surface energy and tendency for agglomeration, which causes rapid attenuation of its mechanical strength and limits its clinical application. At present, the mechanical properties and biocompatibility of nHAp can be effectively improved by loading the related growth factors, proteins, peptides and other bioactive molecules, so as to better meet the biological requirements of bone repair materials. However, the traditional physicochemical modification methods are complicated and may interfere with the bioactivity of nHAp. It is simple to biomimetically synthesize nanomaterials by direct utilization of the molecular recognition and self-assemble capabilities of biomolecules or living microorganisms. Furthermore, the properties of the synthesized nanomaterials are stable, and the method has been extensively studied in recent years. Due to the unique crystaline structure and physicochemical properties of nHAp, results of a large number of studies have shown that its affinity with biological molecules can be used to produce bioactive nHAp by biomimetic synthesis methods. Biomimetically synthesized nHAp is expected to become the mainstream bone tissue engineering scaffold material. Analyzing and summarizing the biomimetic synthetic process and the characteristics of different nHAp materials will facilitate further development of bone defect repair materials with better mechanical and biological properties. Herein we reviewed methods of biomimetic synthesis of nHAp based on different biomolecular templates. Furthermore, we also discussed applications of biomimetic synthesized nHAp in bone tissue engineering, which can used as reference information for further research and development of new-generation bone repair biomaterials.

The role of USP34 in the fixation of titanium implants in murine models.

Ubiquitin-specific protease 34 (USP34), a member of the ubiquitin-specific protease family, regulates osteogenic differentiation of bone marrow mesenchymal stem cells via bone morphogenetic protein signaling. This study aimed to investigate the role of USP34 in fixation of titanium implants in mouse models. Eight-week-old Usp34-knockout (Prx1-Cre;Usp34f/f ) mice and their Usp34 wild-type (Usp34f/f ) control littermates were used. Experimental titanium implants were inserted into the distal ends of femurs and the edentulous area of maxillae. Two and four weeks after surgery, samples of femur and maxilla were obtained, and micro-computed tomography scanning, histomorphometric analyses, and push-in tests were performed on the samples. Compared with controls, Prx1-Cre;Usp34f/f mice showed reduced bone volume for both femurs and maxillae; a decreased femoral bone-implant contact ratio (BIC) at 2 wk [mean (standard error of the mean): 62.17% (2.15%) vs. 44.06% (3.45%)] and 4 wk [72.46% (1.61%) vs. 64.53% (1.93%)]; decreases in femoral bone volume fraction (BV/TV) and push-in resistance; and lower BIC and BV/TV of the maxillae. Taken together, our data demonstrate that specific deletion of Usp34 in mesenchymal stem cells impairs fixation of titanium implants in mice.

Salivary microbiome in patients undergoing hemodialysis and its associations with the duration of the dialysis.

BACKGROUND: Chronic kidney disease (CKD) patients, especially those with end stage renal disease (ESRD) undergoing hemodialysis (HD), exhibit high prevalence of periodontitis. This cross-sectional study aimed to investigate the periodontal status of HD patients and its relationship with salivary microbiome. METHODS: One hundred eight HD patients and one hundred healthy control individuals were recruited. They were subjected to periodontal examination followed by saliva samples collection for 16S rRNA gene sequencing. RESULTS: The HD patients were with worse periodontal health status, and exhibited higher salivary microbial diversity and lower richness. The periodontal pathogens were significantly enriched in the HD patients. The inferred functional analyze showed microbes enriched in the HD patients were mainly related to metabolism. Despite the periodontal status and overall structure of the microbiome were not significantly altered as the HD duration prolonged, the abundance of Lachnospiraceae [G-2] sp. |HMT_096| is positively correlated with the duration of HD and the community periodontal index (CPI). Five OTUs (operational taxonomic units) belonging to the phyla Firmicutes were enriched as the duration prolonged, and four OTUs originated from the phyla Proteobacteria were negatively related with the CPI index. ESRD patients undergoing HD exhibited microbiota structural, compositional and functional differences compared with the healthy controls. And the species changed as the duration of hemodialysis prolonged. CONCLUSIONS: End stage renal disease changes salivary microbiome and is a risk factor for oral dysbiosis.

Periodontal disease and Helicobacter pylori infection in oral cavity: a meta-analysis of 2727 participants mainly based on Asian studies.

OBJECTIVES: To assess the association between periodontal disease and Helicobacter pylori (H. pylori) infection in oral cavity. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, Cochrane library, Gray literature, and clinicaltrials.gov for eligible studies up to September 25, 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The random-effects model was used with the software STATA 13.0. The Newcastle-Ottawa-Scale was used for quality evaluation. RESULTS: Twelve observational studies (eight from Asia, one from Europe, and three from the South America) involving 2727 participants were included in the meta-analysis. The overall pooled results showed that H. pylori infection in oral cavity was associated with periodontal disease (OR 2.53, 95% CI 1.86-3.44, P < 0.05). No significant heterogeneity among the articles was observed (I2 = 44.3%, P < 0.05). The sensitivity analysis indicated that the result of our meta-analysis was generally stable. The Begg test and the Egger test both showed no publication bias was observed (P = 0.45 and P = 0.18 respectively). CONCLUSIONS: Based on current available evidence, it seemed there was a correlation between oral H. pylori infection and the occurrence of periodontal disease. However, since most of the data comes from Asia, more large-scale investigations with high quality from all over the world are needed to confirm the association. CLINICAL RELEVANCE: H. pylori infection in oral may have a positive association with the prevalence of periodontal disease mainly in Asian populations.

Distinct gene expression characteristics in epithelial cell-Porphyromonas gingivalis interactions by integrating transcriptome analyses.

Porphyromonas gingivalis is a pivotal periodontal pathogen, and the epithelial cells serve as the first physical barrier to defend the host from bacterial attack. Within this host-bacteria interaction, P. gingivalis can modify the host immune reaction and adjust the gene expression, which is associated with periodontitis pathogenesis and developing strategies. Herein, a meta-analysis was made to get the differential gene expression profiles in epithelial cells with or without P. gingivalis infection. The network-based meta-analysis program for gene expression profiling was used. Both the gene ontology analysis and the pathway enrichment analysis of the differentially expressed genes were conducted. Our results determined that 290 genes were consistently up-regulated in P. gingivalis infected epithelial cells. 229 gene ontology biological process terms of up-regulated genes were discovered, including "negative regulation of apoptotic process" and "positive regulation of cell proliferation/migration/angiogenesis". In addition to the well-known inflammatory signaling pathways, the pathway associated with a transcriptional misregulation in cancer has also been increased. Our findings indicated that P. gingivalis benefited from the survival of epithelial cells, and got its success as a colonizer in oral epithelium. The results also suggested that infection of P. gingivalis might contribute to oral cancer through chronic inflammation. Negative regulation of the apoptotic process and transcriptional misregulation in cancer pathway are important contributors to the cellular physiology changes during infection development, which have particular relevance to the pathogenesis and progressions of periodontitis, even to the occurrence of oral cancer.

A poly(hydroxyethyl methacrylate)-Ag nanoparticle porous hydrogel for simultaneous in vivo prevention of the foreign-body reaction and bacterial infection.

The use of implants or indwelling medical devices has greatly enhanced the quality and efficacy of health care. However, foreign-body reactions (FBRs) and infections can lead to potential failure or removal of the devices, or increased morbidity and mortality of patients. Herein, we develop a silver nanoparticle (AgNP) loaded poly(hydroxyethyl methacrylate) hydrogel with spherical, interconnected 40 µm pores. The resulting hydrogels displayed good antibacterial properties regarding both gram positive bacteria (Staphylococcus aureus) and gram negative bacteria (Escherichia coli (E. coli)) in vitro and were highly efficient at inhibiting bacterial cell growth. Moreover, they exhibited an in vivo resistance to FBRs by reducing the immune responses, and completely prevented the formation of collagen capsules. Finally, in vivo studies of the E. coli infected mouse model demonstrated that the AgNP loaded porous hydrogels were highly efficient at resisting the bacterial FBRs and infections, while they promoted cell mitigation and infiltration. Findings from this work suggest that AgNP loaded porous hydrogels hold promise in various biomedical applications including in the new generation of implantable biomedical devices and tissue engineering scaffolds.

Co-exposure of decabromodiphenyl ethane and polystyrene nanoplastics damages grass carp (Ctenopharyngodon idella) hepatocytes: Focus on the role of oxidative stress, ferroptosis, and inflammatory reaction.

Decabromodiphenyl ethane (DBDPE) and polystyrene nanoplastics (PS-NPs) are emerging pollutants that seriously threaten the ecological safety of the aquatic environment. However, the hepatotoxicity effect of their combined exposure on aquatic organisms has not been reported to date. In, this study, the effects of single or co-exposure of DBDPE and PS-NPs on grass carp hepatocytes were explored and biomarkers related to oxidative stress, ferroptosis, and inflammatory cytokines were evaluated. The results show that both single and co-exposure to DBDPE and PS-NPs caused oxidative stress. Oxidative stress was induced by increasing the contents of pro-oxidation factors (ROS, MDA, and LPO), inhibiting the activity of antioxidant enzymes (CAT, GPX, T-SOD, GSH, and T-AOC), and downregulating the mRNA expressions of antioxidant genes (GPX1, GSTO1, SOD1, and CAT); the effects of combined exposure were stronger overall. Both single and co-exposure to DBDPE and PS-NPs also elevated Fe2+ content, promoted the expressions of TFR1, STEAP3, and NCOA4, and inhibited the expressions of FTH1, SLC7A11, GCLC, GSS, and GPX4; these effects resulted in iron overload-induced ferroptosis, where co-exposure had stronger adverse effects on ferroptosis-related biomarkers than single exposure. Moreover, single or co-exposure enhanced inflammatory cytokine levels, as evidenced by increased mRNA expressions of IL-6, IL-12, IL-17, IL-18, IL-1ß, TNF-α, IFN-γ, and MPO. Co-exposure exhibited higher expression of pro-inflammatory cytokines compared to single exposure. Interestingly, the ferroptosis inhibitor ferrostatin-1 intervention diminished the above changes. In brief, the results suggest that DBDPE and PS-NPs trigger elevated levels of inflammatory cytokines in grass crap hepatocytes. This elevation is achieved via oxidative stress and iron overload-mediated ferroptosis, where cytotoxicity was stronger under co-exposure compared to single exposure. Overall, the findings contribute to elucidating the potential hepatotoxicity mechanisms in aquatic organisms caused by co-exposure to DBDPE and PS-NPs.

Di (2-ethylhexyl) phthalate and polystyrene microplastics co-exposure caused oxidative stress to activate NF-κB/NLRP3 pathway aggravated pyroptosis and inflammation in mouse kidney.

Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.

Radiopaque and Biocompatible PMMA Bone Cement Triggered by Nano Tantalum Carbide and Its Osteogenic Performance.

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.

Combined exposure of emamectin benzoate and microplastics induces tight junction disorder, immune disorder and inflammation in carp midgut via lysosome/ROS/ferroptosis pathway.

Pesticides and plastics bring convenience to agriculture and life, but also bring residual pollution in the environment. Emamectin benzoate (EMB) is the most popular pesticide at present. The harm of microplastics (MPs) to water and aquatic organisms is gradually increasing, and the possibility that it appears synchronously with various pesticides increases. However, the damage of EMB and MPs to the carp midgut and its mechanism have not been clarified. Therefore, based on the EMB or/and MPs exposure models, this study explored the mechanism of midgut injury through transcriptomics, immunofluorescence, western blot methods, and so on. Studies in vivo and in vitro showed that EMB or MPs exposure caused cilia shortening, lysosome damage, and ROS overproduction, which led to Fe2+ content increase, GSH/GSSG system disorder, lipid peroxidation, and ferroptosis. This process further led to the down-regulation of Cx43, Occludin, Claudin, and ZO-1, which further caused barrier damage, immune-related genes (immunoglobulin, IFN-γ) decrease and inflammation-related genes (TNF-α, IL-1ß) increase. Combined exposure was more significant than that of single exposure, and the addition of EN6 and NAC proved that lysosome/ROS/ferroptosis regulated these midgut damages. In conclusion, EMB or/and MPs exposure induce tight junction disorder, immune disorder and inflammation in carp midgut through the lysosome/ROS/ferroptosis pathway.

Ultrasound-propelled liposome circumvention and siRNA silencing reverse BRAF mutation-arised cancer resistance to trametinib.

BRAF-V600E mutation is regarded as the source of lung cancer resistance to trametinib (Tr), and no solution available for completely addressing this intractable resistance has emerged yet. Herein, the combination of ultrasonic (US) propelled folic acid (FA)-modified liposomes strategy and BRAF-driven gene silencing program is proposed to effectively reverse Tr's resistance to lung cancer. Meanwhile, the prepared cationic nanoliposomes can assist Tr drug and BRAF siRNA to escape lysosome disposal, thereby avoiding Tr drug pumping out or siRNA degradation. More significantly, loaded BRAF siRNA is designed to silence BRAF-V600E mutation genes via modulating BRAF-ERK-pathway and remarkably reverse the PC9R resistance to Tr. Systematic experiments validate that these cooperatively sensitize PC9R cells to Tr and shrink resistant NSCLC in vivo, especially after combining with FA-mediated targeting and US-enhanced permeability that permits more intratumoral accumulations of Tr. Such a biocompatible targeting drug-resistance liberation agent and its underlying design strategy lay a foundation avenue to completely reverse tumor resistance, which is preferable to treat BRAF mutation-arised resistance of various tumors, holding high clinical translation potentials.

[Occurrence Characteristics of Microplastics in Multi-environmental Media and Bellamya aeruginosa of Manao River].

Microplastic pollution poses threats to aquatic ecosystems and human health. In this study, in order to investigate the characteristics of microplastic occurrence in different environmental media, the abundance, particle size, shape, color, and composition types of microplastics in the water column, sediment, riparian zone soil, and the benthic snail Bellamya aeruginosa of the Manao River were analyzed using field sampling, microscopic observation, and Fourier infrared spectroscopy. The results showed that the average abundance of microplastics in the surface water of the Manao River was (5.9±0.26) n·L-1; the abundance of microplastics in the upper sediment (by dry weight) was (1.35±0.1) n·g-1, and that in the lower sediment (by dry weight) was (0.93±0.12) n·g-1. The abundance of microplastics in the near riparian zone soil (by dry weight) was (0.68±0.16) n·g-1, and that in the far riparian zone soil (by dry weight) was (0.69±0.14) n·g-1, and the abundance of microplastics in the B. aeruginosa was (2.06±0.25) n·g-1. The analysis results showed that the abundance of microplastics in the upper and lower sediments were positively correlated; the abundance of microplastics in B. aeruginosa was positively correlated with the abundance of microplastics in the upper and lower sediments, respectively; and the abundance of microplastics in the near and far riparian zone soils were also correlated. Most of the microplastics within each environmental medium and B. aeruginosa were <0.1 mm in size, mainly in the form of fibers and fragments, mainly blue and black in color, and mainly composed of polypropylene (PP) and polyethylene (PE). It was found that microplastics in riparian zone soils mainly originated from the fragmentation and decomposition of agricultural plastic films. The results of this study shed light on the accumulation of microplastics in macrobenthic organisms through the investigation of microplastics in multi-environmental media and in the B. aeruginosa, which helps us to understand the potential ecological risk of microplastics in a comprehensive manner.

Combined negative effects of microplastics and plasticizer DEHP: The increased release of Nets delays wound healing in mice.

Environmental harmful pollutants microplastics (MPs) and di (2-ethyl) hexyl phthalate (DEHP) are widely residual in the environment, which may cause lesion to multiple apparatus by inducing oxidative stress, threatening the health of human and animals. Neutrophil extracellular traps (Nets) are involved in skin wound healing. Most studies focused on the individual effects of different poisons on animals and ecosystems, but there are few studies on the accumulation and interaction of multiple poisons. The purpose of this study is to explore the effect of DEHP and MPs co-exposure on skin wound healing and the formation of Nets. For this purpose, we detected this hypothesis by replicating the DEHP and MPs-exposed skin wound model in mice, as well as the co-culture system of neutrophil and fibroblast. The results displayed that MPs and DEHP exposure delayed skin healing, which was more pronounced in the combined exposure group. In vitro and in vivo experiments confirmed that compared with the DEHP or MPs group, the DEHP+MPs group had more significant oxidative stress, increased Nets release and inflammatory factors, and inhibited the Wnt/ß-catenin pathway and fibrosis-related factors. N-acetylcysteine (NAC) attenuated these phenomena. Through the co-culture system, we confirmed that the overproduction of Nets induced fibroblasts to exacerbate inflammatory responses and inhibit Wnt pathway and fibrosis. Overall, DEHP and MPs can produce synergistic toxic injury in mice skin wounds, and the excessive activation of ROS/Nets can aggravate inflammatory and inhibit fibrosis, resulting in delayed wound healing.