Effect of early cannulation with metal needles on arteriovenous fistula patency in patients undergoing hemodialysis.

BACKGROUND: Autogenous arteriovenous fistula (AVF) is the preferred vascular access mode. However, the earliest possible time for AVF puncture and whether premature puncture affects the AVF patency rate remain unclear. METHODS: In this multicenter retrospective cohort study, adult uremic patients who underwent AVF surgery for the first time at Taizhou Hospital or Enze Hospital of Zhejiang Province between September 1, 2018 and August 31, 2021 were enrolled. All patients were followed up for 1 year after puncture, and the status of fistula establishment and puncture, subsequent patency, loss to follow-up, renal transplantation, conversion to peritoneal dialysis, abandonment of the fistula, and death, were recorded. RESULTS: A total of 465 patients with AVFs were included in this study, including 59 (12.7%) patients with fistulas that were cannulated within 30 days. In the early puncture group, the levels of serum creatinine and urea nitrogen were higher, while the levels of hemoglobin and albumin were lower, suggesting that these patients needed urgent dialysis. Furthermore, the rate of non-cuffed catheter use was higher, while the rate of cuffed catheter use was lower, and femoral vein puncture was preferred over internal jugular vein puncture. The mean duration of catheter indwelling was shorter in the early puncture group (19 vs 70 days, p < 0.001). The estimated AVF primary and cumulative functional patency at 12 months was 81.1% versus 82.3% and 98.3% versus 98.7% in the early puncture and control groups, respectively. Kaplan-Meier analysis revealed no significant difference in AVF primary and cumulative functional patency between the two groups. CONCLUSIONS: In patients with an established fistula in urgent need of hemodialysis, to avoid new catheterization, a puncture can be performed within 30 days in those with well-developed blood vessels after adequate ultrasound and clinical evaluation without affecting the patency of the fistula.

Enhancing Tumor Immunotherapy by Multivalent Anti-PD-L1 Nanobody Assembled via Ferritin Nanocage.

Increasing immunotherapy response rate and durability can lead to significant improvements in cancer care. To address this challenge, a novel multivalent immune checkpoint therapeutic platform is constructed through site-specific ligation of anti-PD-L1 nanobody (Nb) on ferritin (Ftn) nanocage. Nb-Ftn blocks PD-1/PD-L1 interaction and downregulates PD-L1 levels via endocytosis-induced degradation. In addition, the cage structure of Ftn allows encapsulation of indocyanine green (ICG), an FDA-approved dye. Photothermal treatment with Nb-Ftn@ICG induces immunogenic death of tumor cells, which improves systemic immune response via maturation of dendritic cells and enhanced infiltration of T cells. Moreover, Nb-Ftn encapsulation significantly enhances cellular uptake, tumor accumulation and retention of ICG. In vivo assays showed that this nanoplatform ablates the primary tumor, suppresses abscopal tumors and inhibits tumor metastasis, leading to a prolonged survival rate. This work presents a novel strategy for improving cancer immunotherapy using multivalent nanobody-ferritin conjugates as immunological targeting and enhancing carriers.

A non-metal single atom nanozyme for cutting off the energy and reducing power of tumors.

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.

Amorphous RuPd bimetallene for hydrogen evolution reaction in acidic and alkaline conditions: a first-principles study.

Metallene materials can provide a large number of active catalytic sites for the efficient use of noble metals as catalysts for hydrogen evolution reaction (HER), whereas the intrinsic activity on the surface is insufficient in crystal phase. The amorphous phase with an inherent long-range disorder can offer a rich coordinate environment and charge polarization on the surface is proposed for promoting the intrinsic catalytic activity on the surface of noble metals. Herein, we designed an amorphous RuPd (am-RuPd) structure by the first principles molecular dynamics method. The performance of the acidic HER on am-RuPd can have a huge enhancement due to the free energy change of hydrogen adsorption close to zero. In alkaline conditions, the H2O dissociation energy barrier on am-RuPd is just 0.49 eV, and it is predicted that the alkaline HER performance of am-RuPd will largely exceed that of Pt nanocrystalline sheets. This work provides a strategy for enhancing the intrinsic catalytic activity on the surface and a way to design an efficient HER catalyst based on metallene materials used in both acidic and alkaline conditions.

Bacteriocins: Curial guardians of gastrointestinal tract.

The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.

Role of folic acid in regulating gut microbiota and short-chain fatty acids based on an in vitro fermentation model.

Folic acid deficiency is common worldwide and is linked to an imbalance in gut microbiota. However, based on model animals used to study the utilization of folic acid by gut microbes, there are challenges of reproducibility and individual differences. In this study, an in vitro fecal slurry culture model of folic acid deficiency was established to investigate the effects of supplementation with 5-methyltetrahydrofolate (MTHF) and non-reduced folic acid (FA) on the modulation of gut microbiota. 16S rRNA sequencing results revealed that both FA (29.7%) and MTHF (27.9%) supplementation significantly reduced the relative abundance of Bacteroidetes compared with control case (34.3%). MTHF supplementation significantly improved the relative abundance of Firmicutes by 4.49%. Notably, compared with the control case, FA and MTHF supplementation promoted an increase in fecal levels of Lactobacillus, Bifidobacterium, and Pediococcus. Short-chain fatty acid (SCFA) analysis showed that folic acid supplementation decreased acetate levels and increased fermentative production of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a model of folic acid deficiency in humans to study the gut microbiota and demonstrate that exogenous folic acid affects the composition of the gut microbiota and the level of SCFAs. KEY POINTS: • Establishment of folic acid deficiency in an in vitro culture model. • Folic acid supplementation regulates intestinal microbes and SCFAs. • Connections between microbes and SCFAs after adding folic acid are built.

Comparison of the perinatal outcomes of expected high ovarian response patients and normal ovarian response patients undergoing frozen-thawed embryo transfer in natural/small amount of HMG induced ovulation cycles.

BACKGROUND: Due to the high risk of complications in fresh transfer cycles among expected high ovarian response patients, most choose frozen-thawed embryo transfer (FET). There are currently few researches on whether the FET outcomes of expected high ovarian response patients with regular menstrual cycles are similar to those of normal ovarian response. Therefore, our objective was to explore and compare pregnancy outcomes and maternal and neonatal outcomes of natural FET cycles between patients with expected high ovarian response and normal ovarian response with regular menstrual cycles based on the antral follicle count (AFC). METHODS: This retrospective cohort study included 5082 women undergoing natural or small amount of HMG induced ovulation FET cycles at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2017, to March 31, 2021. The population was divided into expected high ovarian response group and normal ovarian response group based on the AFC, and the differences in patient characteristics, clinical outcomes and perinatal outcomes between the two groups were compared. RESULTS: Regarding clinical outcomes, compared with the normal ovarian response group, patients in the expected high ovarian response group had a higher clinical pregnancy rate (57.34% vs. 48.50%) and live birth rate (48.12% vs. 38.97%). There was no difference in the early miscarriage rate or twin pregnancy rate between the groups. Multivariate logistic regression analysis suggested that the clinical pregnancy rate (adjusted OR 1.190) and live birth rate (adjusted OR 1.171) of the expected high ovarian response group were higher than those of the normal ovarian response group. In terms of maternal and infant outcomes, the incidence of very preterm delivery in the normal ovarian response group was higher than that in the expected high ovarian response group (0.86% vs. 0.16%, adjusted OR 0.131), Other maternal and infant outcomes were not significantly different. After grouping by age (< 30 y, 30-34 y, 35-39 y), there was no difference in the incidence of very preterm delivery among the age subgroups. CONCLUSION: For patients with expected high ovarian response and regular menstrual cycles undergoing natural or small amount of HMG induced ovulation FET cycles, the clinical and perinatal outcomes are reassuring. For patients undergoing natural or small amount of HMG induced ovulation FET cycles, as age increases, perinatal care should be strengthened during pregnancy to reduce the incidence of very preterm delivery.

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

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

Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD.

AIM: Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat-containing 2 (BIRC2) and tumor necrosis factor receptor 1-associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA. METHODS: C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real-time polymerase chain reaction and western blot. Cell Counting Kit-8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro-inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co-immunoprecipitation assay. RESULTS: BIRC2 and TRADD were discovered to be highly expressed in LPS-mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS-induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS-mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression. CONCLUSION: In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS-mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.

A Leaking-Proof Theranostic Nanoplatform for Tumor-Targeted and Dual-Modality Imaging-Guided Photodynamic Therapy.

Objective: A protein-based leaking-proof theranostic nanoplatform for dual-modality imaging-guided tumor photodynamic therapy (PDT) has been designed. Impact Statement: A site-specific conjugation of chlorin e6 (Ce6) to ferrimagnetic ferritin (MFtn-Ce6) has been constructed to address the challenge of unexpected leakage that often occurs during small-molecule drug delivery. Introduction: PDT is one of the most promising approaches for tumor treatment, while a delivery system is typically required for hydrophobic photosensitizers. However, the nonspecific distribution and leakage of photosensitizers could lead to insufficient drug accumulation in tumor sites. Methods: An engineered ferritin was generated for site-specific conjugation of Ce6 to obtain a leaking-proof delivery system, and a ferrimagnetic core was biomineralized in the cavity of ferritin, resulting in a fluorescent ferrimagnetic ferritin nanoplatform (MFtn-Ce6). The distribution and tumor targeting of MFtn-Ce6 can be detected by magnetic resonance imaging (MRI) and fluorescence imaging (FLI). Results: MFtn-Ce6 showed effective dual-modality MRI and FLI. A prolonged in vivo circulation and increased tumor accumulation and retention of photosensitizer was observed. The time-dependent distribution of MFtn-Ce6 can be precisely tracked in real time to find the optimal time window for PDT treatment. The colocalization of ferritin and the iron oxide core confirms the high stability of the nanoplatform in vivo. The results showed that mice treated with MFtn-Ce6 exhibited marked tumor-suppressive activity after laser irradiation. Conclusion: The ferritin-based leaking-proof nanoplatform can be used for the efficient delivery of the photosensitizer to achieve an enhanced therapeutic effect. This method established a general approach for the dual-modality imaging-guided tumor delivery of PDT agents.

Femtosecond-laser-assisted high-aspect-ratio nanolithography in lithium niobate.

We report the successful fabrication of high-aspect-ratio lithium niobate (LN) nanostructures by using femtosecond-laser-assisted chemical etching. In this technique, a 1 kHz femtosecond laser is first used to induce local modifications inside the LN crystal. Then, selective chemical wet etching is conducted using a buffered oxide etch (BOE) solution. The etching rate in the laser-modified area reaches 2 µm h-1, which is enhanced by a factor of ∼660 in comparison to previous reports without laser irradiation. Such high selectivity in chemical etching helps realize high-performance maskless nanolithography in lithium niobate. In the experiment, we have fabricated high-quality LN nanohole arrays. The nanohole size reaches ∼100 nm and its aspect ratio is above 40 : 1. The minimal period of the LN hole array is 300 nm. Our work paves a way to fabricate LN nano-integrated devices for advanced optic and electronic applications.

A transposon-derived gene family regulates heading date in rice.

As a consequence of transposon domestication, transposon-derived proteins often acquire important biological functions. However, there have been limited studies on transposon-derived proteins in rice, and a systematic analysis of transposon-derived genes is lacking. Here, for the first time, we conducted a comprehensive analysis of the DDE_Tnp_4 (DDE) gene family, which originated from transposons but lost their transpositional ability and acquired new gene functions in Oryza species. A total of 58 DDE family genes, categorized into six groups, were identified in Oryza species, including 13 OsDDE genes in Oryza sativa ssp. japonica. Our analysis indicates that gene duplication events were not the primary mechanism behind the expansion of OsDDE genes in rice. Promoter cis-element analysis combined with haplotype analysis confirmed that OsDDEs regulate the heading date in rice. Specifically, OsDDE9 is a nuclear-localized protein expressed ubiquitously, which promotes heading date by regulating the expression of Ghd7 and Ehd1 under both short-day and long-day conditions. Single-nucleotide polymorphism (SNP) variations in the OsDDE9 promoter leads to changes in promoter activity, resulting in variations in heading dates. This study provides valuable insights into the molecular function and mechanism of the OsDDE genes.

Season and temperature do not affect cumulative live birth rate and time to live birth in in vitro fertilization.

Objective: To explore whether season and temperature on oocyte retrieval day affect the cumulative live birth rate and time to live birth. Methods: This was a retrospective cohort study. A total of 14420 oocyte retrieval cycles from October 2015 to September 2019. According to the date of oocyte retrieval, the patients were divided into four groups (Spring(n=3634);Summer(n=4414); Autumn(n=3706); Winter(n=2666)). The primary outcome measures were cumulative live birth rate and time to live birth. The secondary outcome measures included the number of oocytes retrieved, number of 2PN, number of available embryos and number of high-quality embryos. Results: The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (p=0.04), and number of high-quality embryos (p<0.01) were different among the groups. The quality of embryos in summer was relatively poor. There were no differences between the four groups in terms of cumulative live birth rate (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression, temperature (P=0.80), season (P=0.47) and duration of sunshine(P=0.46) had no effect on cumulative live births. Only maternal age (P<0.01) and basal FSH (P<0.01) had an effect on cumulative live births. Cox regression analysis suggested no effect of season(P=0.18) and temperature(P=0.89) on time to live birth. Maternal age did have an effect on time to live birth (P<0.01). Conclusion: Although season has an effect on the embryo, there was no evidence that season or temperature affect the cumulative live birth rate or time to live birth. It is not necessary to select a specific season when preparing for IVF.

The regulation function of intestinal microbiota by folate-producing Lactiplantibacillus plantarum LZ227.

BACKGROUND: Folic acid is a class of B vitamins that have the function of improving intestinal microbiota. RESULT: Lactiplantibacillus plantarum LZ227, which is a highly folate-producing strain, was used as the research object, and the folic acid produced by LZ227 was further identified by liquid chromatography-mass spectrometry, and the structural diversity, community composition, abundance difference, and short-chain fatty acids content in fermentation broth were studied by the manure slurry fermentation model. The results showed that the folic acid produced by LZ227 was 5-methyltetrahydrofolate. CONCLUSION: LZ227 can increase the intestinal microbial diversity in the folate-free state, regulate the intestinal flora, increase the abundance of Firmicutes in the intestinal flora, and inhibit the abundance of Bacteroidetes. LZ227 can inhibit the growth of Alistipes, Parabacteroides, and Bacteroides in the intestine. LZ227 significantly reduced the acetic acid content and significantly increased the butyric acid content in the folate-free case. © 2023 Society of Chemical Industry.

Gas-Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy.

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting healing are critical considerations in the development of PTT. Here, we proposed a gas-mediated energy remodeling strategy to improve mild PTT efficacy while minimizing side effects. In the proof-of-concept study, a Food and Drug Administration (FDA)-approved drug-based hydrogen sulfide (H2 S) donor was developed to provide a sustained supply of H2 S to tumor sites, serving as an adjuvant to PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to be a universal solution for overcoming the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoagents.

Subsequent fertility after cesarean scar pregnancy: a retrospective analysis.

BACKGROUND: Cesarean scar pregnancy (CSP) refers to the implantation and growth of the gestational sac at a uterine scarring site due to a previous cesarean section. The effects of CSP on subsequent fertility have emerged as a clinical issue of importance in gynecology and obstetrics in China owing to the increasing rate of cesarean section over the past 30 years in combination with the abolition of the national family planning policy, allowing for subsequent pregnancies. Therefore, we aimed to investigate the effects of CSP treatment on subsequent fertility and pregnancy outcomes. METHODS: The study consecutively enrolled 499 women treated for CSP at Taizhou Hospital between January 2009 and December 2018. The study outcomes were the rate of secondary infertility and pregnancy outcomes. Clinical information was collected at the time of admission for CSP treatment. Information on subsequent fertility and pregnancy outcomes was collected via telephonic follow-up. RESULTS: Among the 499 women who met the inclusion criteria for CSP, 48 were lost to follow-up. Most women (74.9%, 338/451) did not express the desire for a subsequent pregnancy after CSP treatment. Among the 113 women who initially desired a subsequent pregnancy, 62 finally abandoned fertility plans. Among the 51 women who pursued pregnancy, 48 pregnancies were recorded in 43 women, infertility secondary to CSP treatment was identified in 15.7% (8/51) of women, and 60.8% (31/51) of women achieved full-term pregnancy, with placenta accreta spectrum identified in two women, one requiring a hysterectomy during cesarean section due to massive bleeding. Among the 16 women treated with uterine artery embolization combined with uterine aspiration and 18 women treated by ultrasound-guided local lauromacrogol injection combined with uterine aspiration, a successful full-term pregnancy rate of 68.8% (11/16) and 88.9% (16/18), respectively, was achieved. There were five cases of recurrent CSP among all 76 pregnancies (6.6%). CONCLUSION: Over a long-term follow-up of women after CSP treatment, a high successful fertility rate was identified, with also an increased CSP recurrence rate. Uterine artery embolization combined with uterine aspiration and ultrasound-guided local lauromacrogol injection combined with uterine aspiration showed high rates of successful post-treatment fertility and pregnancy.

Integrating Widely Targeted Lipidomics and Transcriptomics Unravels Aberrant Lipid Metabolism and Identifies Potential Biomarkers of Food Allergies in Rats.

SCOPE: Oral food challenges (OFCs) are currently the gold standard for determining the clinical reactivity of food allergy (FA) but are time-consuming, expensive, and risky. To screen novel peripheral biomarkers of FA and characterize the aberrant lipid metabolism in serum, 24 rats are divided into four groups: peanut, milk, and shrimp allergy (PA, MA, and SA, respectively) and control groups, with six rats in each group, and used for widely targeted lipidomics and transcriptomics analysis. METHODS AND RESULTS: Widely targeted lipidomics reveal 144, 162, and 206 differentially accumulated lipids in PA, MA, and SA groups, respectively. The study integrates widely targeted lipidomics and transcriptomics and identifies abnormal lipid metabolism correlated with widespread differential accumulation of diverse lipids (including triacylglycerol, diacylglycerol, sphingolipid, and glycerophospholipid) in PA, MA, and SA. Simplified random forest classifier is constructed through five repetitions of 10-fold cross-validation to distinguish allergy from control. A subset of 15 lipids as potential biomarkers allows for more reliable and more accurate prediction of FA. Independent replication validates the reproducibility of potential biomarkers. CONCLUSION: The results reveal the major abnormalities in lipid metabolism and suggest the potential role of lipids as novel molecular signatures for FA.

Astrocytes-derived exosomes pre-treated by berberine inhibit neuroinflammation after stroke via miR-182-5p/Rac1 pathway.

BACKGROUND: Our previous studies have shown that berberine can improve the nerve function deficits in ischemic stroke by inhibiting inflammation. The cellular communication between astrocytes and neurons via exosomes might affect neurological function after ischemic stroke, which plays a vital role in the therapy of ischemic stroke. OBJECTIVE: The present study focused on the effects of exosomes released from astrocytes induced by the glucose and oxygen deprivation model with berberine pretreatment (BBR-exos) treatment for ischemic stroke and its regulatory mechanism. METHODS: Oxygen-glucose-deprivation/Reoxygenation (OGD/R)-treated primary cells were used to mimic cerebral ischemia/reperfusion conditions in vitro. With the treatment of BBR-exos and exosomes released from primary astrocytes induced by the glucose and oxygen deprivation model (OGD/R-exos), the cell viability was detected. C57BL/6J mice were used to establish middle cerebral artery occlusion/reperfusion (MCAO/R) model. The anti-neuroinflammation effects of BBR-exos and OGD/R-exos were evaluated. Subsequently, the key miRNA in BBR-exos was identified by exosomal miRNA sequencing and cell validation. miR-182-5p mimic and inhibitors were provided to verify the effects in inflammation. Finally, the binding sites between miR-182-5p and Rac1 were predicted online and verified by using a dual-luciferase reporter assay. RESULTS: BBR-exos and OGD/R-exos both improved the decreased activity of OGD/R-induced neurons, and decreased the expression of IL-1ß, IL-6 and TNF-α (all P ＜ 0.05), which reduced neuronal injury and inhibited neuroinflammation in Vitro. And BBR-exos showed better effects (P ＜ 0.05). The same effect has been verified in vivo experiments: BBR-exos and OGD/R-exos both reduced cerebral ischemic injury and inhibited neuroinflammation in MCAO/R mice (all P ＜ 0.05). Likewise, BBR-exos showed better effects (P ＜ 0.05). The exosomal miRNA sequencing results showed that miR-182-5p was highly expressed in BBR-exos and inhibited neuroinflammation by targeting Rac1 (P ＜ 0.05). CONCLUSION: BBR-exos can carry miR-182-5p to injured neurons and inhibit the expression of Rac1, which could inhibit neuroinflammation and improved brain injury after ischemic stroke.

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

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