A dual computational and experimental strategy to enhance TSLP antibody affinity for improved asthma treatment.

Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis. Subsequent mutations and experimental validations resulted in an antibody with significantly enhanced blocking capacity against TSLP. Our findings demonstrate the potential of computer-assisted techniques in expediting antibody affinity maturation, thereby reducing both the time and cost of experiments. The integration of computational methods with experimental approaches holds great promise for the development of targeted therapeutic antibodies for TSLP-related diseases.

STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation.

Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.

Rapid Analysis of Estrogens in Meat Samples by High Performance Liquid Chromatography with Fluorescence Detection.

A novel reagent named 4-(N-methyl-1,3-dioxo-benzoisoquinolin-6-yl-oxy)benzene sulfonyl chloride (MBIOBS-Cl) for the determination of estrogens in food samples by high-performance liquid chromatography (HPLC) with fluorescence detection has been developed. Estrogens could be easily labeled by MBIOBS-Cl in Na2CO3-NaHCO3 buffer solution at pH 10.0. The complete labeling reaction for estrogens could be accomplished within five minutes, the corresponding derivatives exhibited strong fluorescence with the maximum excitation and emission wavelengths at 249 nm and 443 nm, respectively. The derivatization conditions, such as the molar ratio of reagent to estrogens, derivatization time, pH, temperature, and buffers were optimized. Derivatives were sufficiently stable to be efficiently analyzed by HPLC with a reversed-phase Agilent ZORBAX 300SB-C18 column with a good baseline resolution. Excellent linear correlations were obtained for all estrogen derivatives with correlation coefficients greater than 0.9998. Ultrasonic-Assisted extraction was used to optimize the extraction of estrogens from meat samples with a recovery higher than 82%. The detection limits (LOD, S/N = 3) of the method ranged from 0.95 to 3.3 µg· kg-1. The established method, which is fast, simple, inexpensive, and environment friendly, can be successfully applied for the detection of four steroidal estrogens from meat samples with little matrix interference.

A novel 2-(2-aminophenyl) imidazo [1,5-a] pyridine-based fluorescent probe for rapid detection of phosgene.

Phosgene is a highly concealed and highly toxic gas that seriously threatens human health and public security. Therefore, the detection of phosgene is of great significance to world security. Herein, a new type of fluorescent probe based on 2-(2-aminophenyl) imidazo [1,5-a] pyridine is reported for the rapid detection of phosgene. The probe itself only emits a faint green fluorescence, while phosgene allows it to produce a strong blue fluorescence. During the recognition process, phosgene interacts simultaneously with both amino site and imidazole moiety in the probe molecule, resulting in a four-ring-fused rigid structure with high fluorescence quantum yield. The probe not only has the characteristics of high efficiency, high sensitivity (detection limit 2.68 nM), and high selectivity, but also has remarkable spectral changes. Finally, a portable test strip is used to detect phosgene in the gas phase, and the fluorescent color change of the test strip can be easily observed. The most exciting thing is that the portable test strip with the probe PMPY-NH2 can produce a strong fluorescence response to 1 ppm of phosgene, which is far lower than the level of phosgene that seriously threatens to human health.

Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling.

BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation. CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.

Comprehensive pulmonary metabolic responses to silica nanoparticles exposure in Fisher 344 rats.

Silica nanoparticles (SiNPs) could induce adverse pulmonary effects, but the mechanism was not clear enough. Metabolomics is a sensitive and high-throughput approach that could investigate the intrinsic causes of adverse health effects caused by SiNPs. The current investigation represented the first in vivo metabolomics study examining the chronic pulmonary toxicity of SiNPs at a low dosage, mimicking real human exposure situation. The recovery process after the cessation of exposure was also taken into consideration. Fisher 344 rats were treated with either saline or SiNPs for 6 months. Half of the animals in each group received an additional six-month period for recovery. The findings indicated that chronic low-level exposure to SiNPs resulted in notable alterations in pulmonary metabolism of amino acids, lipids, carbohydrates, and nucleotides. SiNPs exerted an impact on various metabolites and metabolic pathways which are linked to oxidative stress, inflammation and tumorigenesis. These included but were not limited to L-carnitine, spermidine, taurine, xanthine, and glutathione metabolism. The metabolic alterations caused by SiNPs exhibited a degree of reversibility. However, the interference of SiNPs on two metabolic pathways related to tumorigenesis was observed to persist after a recovery period. The two metabolic pathways are glycerophospholipid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis. This study elucidated the metabolic alterations induced by chronic low-level exposure to SiNPs and presented novel evidence of the chronic pulmonary toxicity and carcinogenicity of SiNPs, from a metabolomic perspective.

The size-dependent in vivo toxicity of amorphous silica nanoparticles: A systematic review.

The extensive application of amorphous silica nanoparticles (aSiNPs) in recent years has resulted in unavoidable human exposure in daily life, thus raising widespread concerns regarding the safety of aSiNPs on human health. The particle size is one of the important characteristics of nanomaterials that could influence their toxicity. For the reason that particles with smaller sizes possess larger surface area, which may lead to higher surface activity and biological reactivity. However, due to the complexity of experimental conditions and biological systems, the relationship between the particle size and the toxic effect of aSiNPs remains unclear. Therefore, this systematic review aims to investigate how particle size influences the toxic effect of aSiNPs in vivo and to analyze the relevant experimental factors affecting the size-dependent toxicity of aSiNPs in vivo. We found that 83.8% of 35 papers included in the present review came to the conclusion that smaller-sized aSiNPs exhibited stronger toxicity, though a few papers (6 papers) put forward different opinions. The reasons for smaller aSiNPs manifested greater toxicity were summarized. In addition, certain important experimental factors could influence the size-dependent effects and in vivo toxicity of aSiNPs, such as the synthesis method of aSiNPs, disperse medium of aSiNPs, administration route of aSiNPs, species or strain of experimental animals, sex of experimental animals, aggregation/agglomeration and protein corona of aSiNPs.

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles.

Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3Ⅱ/LC3Ⅰ increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.

Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd.

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.

Melatonin ameliorates PM2.5-induced spermatogenesis disorder by preserving H3K9 methylation and SIRT3.

There was a link between exposure to PM2.5 and male infertility. Melatonin has beneficial effects on the male reproductive processes. How PM2.5 caused spermatogenesis disturbance and whether melatonin could prevent PM2.5-induced reproductive toxicity have remained unclear. The results showed that PM2.5 could inhibit the Nrf2-mediated antioxidant pathway and distinctly increase the cell apoptosis in testes. Moreover, PM2.5 also perturbed the process of meiosis by modulating meiosis-associated proteins such as γ-H2AX and Stra8. Mechanistically, PM2.5 inhibited G9a-dependent H3K9 methylation and SIRT3-mediated p53 deacetylation, which consistent with decreased sperm count and motility rate in ApoE-/- mice. Further investigation revealed melatonin effectively alleviated PM2.5-induced meiosis inhibition by preserving H3K9 methylation. Melatonin also alleviated PM2.5-induced apoptosis by regulating SIRT3-mediated p53 deacetylation. Overall, our study revealed PM2.5 resulted in spermatogenesis disorder by perturbing meiosis via G9a-dependent H3K9 di-methylation and causing cell apoptosis via SIRT3/p53 deacetylation pathway and provided promising insights into the protective role of melatonin in air pollution associated with male infertility.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

Disentangling the effects of geographic distance, environment and history on beta diversity of freshwater fish at a biogeographical crossroads.

Examining assemblage turnover and variation along geographic and environmental distances is a useful approach to evaluate beta diversity patterns and associated driving mechanisms. However, such studies are relatively limited in freshwater systems. Here, we compared the relationships between freshwater fish beta diversity and geographic distances among 165 hydrological units (HUs) in four zoogeographical regions (PA, Palearctic Region; CA, High Central Asia; EA, East Asia, SA, South Asia) across China and adjacent areas. This area can be considered a biogeographical crossroads, where faunal composition shares elements with different biogeographic and evolutionary origins. We found a considerably high level of between-HU overall dissimilarity (ßsor, range from ca. 0.60 to 0.85) in all four regions, mainly due to the turnover component (the relative contribution of ßsim to ßsor ranged from 60% to 90%). In general, ßsor and ßsim both significantly increased with geographic distance (except in PA), whereas the nestedness-resultant component (ßsne) decreased with geographic distance. The intercepts and slopes of the relationships between dissimilarities and distance (RDDs) both varied significantly among the four regions. The intercepts of ßsor and ßsim were both highest in SA, followed by CA, PA and EA, implying different levels of fish faunal heterogeneity at short distances. In contrast, the slopes of these two dissimilarities followed the decreasing trend from EA > CA > SA > PA, suggesting different environmental suitability and dispersal ability of fish species among regions. Variation partitioning in distance-based redundancy analysis showed that the spatial and historical factors were more important than area-heterogeneity and energy factors across all HUs and within three individual ecoregions (EA, SA and CA), but spatial factors were non-significant in PA. Our study highlighted the usefulness of RDDs in understanding biogeographical patterns and enhancing the biodiversity conservation of freshwater fishes.

Silica Nanoparticles Trigger Chaperone HSPB8-Assisted Selective Autophagy via TFEB Activation in Hepatocytes.

Silica nanoparticles (SiNPs) are one of the most common inorganic nanomaterials. Autophagy is the predominant biological response to nanoparticles and transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway. Previous studies show that SiNPs induce autophagosome accumulation, yet the precise underlying mechanisms remain uncertain. The present study investigates the role of TFEB during SiNP-induced autophagy. SiNP-induced TFEB nuclear translocation is verified using immunofluorescence and western blot assay. The regulation of TFEB is proved to be via EIF2AK3 pathway. A TFEB knockout (KO) cell line is constructed to validate the TFEB involvement in SiNP-induced autophagy. The transcriptomes of wild-type and TFEB KO cells are compared using RNA-sequencing to identify genes of the TFEB-mediated autophagy and lysosome pathways affected by SiNPs. Based on these data and the Human Autophagy Database, four candidate autophagic genes are identified, including HSPB8, ATG4D, CTSB and CTSD. Specifically, that the chaperone HSPB8 is upregulated through SiNP-mediated TFEB activation and forms a chaperone-assisted selective autophagy (CASA) complex with BAG3 and HSC70, triggering HSPB8-assisted selective autophagy, is found. Thus, this study characterizes a novel mechanism underlying SiNP-induced autophagy that helps pave the way for further research on the toxicity and risk assessment of SiNPs.

Reflective one-to-multi-polarization conversion via separate control of phase and magnitude.

Polarization manipulation is a key issue in electromagnetic (EM) research. Research on 90° polarization rotators and circularly-polarized wave generators has been widely conducted. In this study, a polarization conversion metasurface that can shift one linearly-polarized EM wave into multi-polarization outgoing waves at certain frequencies is demonstrated, including co-, cross-, left-hand, and right-hand circular-polarization components. The surface was made of periodically arranged chiral meta-atoms. The polarization manipulation method is based on the independent control of phase and magnitude, in which the phase control is based on the Berry-phase theory of linearly-polarized EM waves, while the magnitude control is based on the cavity mode theory of the microstrip structure. Both eigenmode analysis (EMA) and characteristic mode analysis (CMA) were utilized for magnitude control, which was further verified by the surface current distribution. Finally, the metasurface was fabricated and measured, showing good agreement between the measured and simulated results. This research proposed what we believe to be a novel polarization method, which can be potentially applied in polarization manipulation, EM radiation, filters, wireless sensors, etc., over a frequency range from optics to microwave bands.

Ambient Fine Particulate Matter and Cancer: Current Evidence and Future Perspectives.

The high incidence of cancer has placed an enormous health and economic burden on countries around the world. In addition to evidence of epidemiological studies, conclusive evidence from animal experiments and mechanistic studies have also shown that morbidity and mortality of some cancers can be attributed to ambient fine particulate matter (PM2.5) exposure, especially in lung cancer. However, the underlying carcinogenetic mechanisms of PM2.5 remain unclear. Furthermore, in terms of risks of other types of cancer, both epidemiological and mechanistic evidence are more limited and scattered, and the results are also inconsistent. In order to sort out the carcinogenic effect of PM2.5, this paper reviews the association of cancers with PM2.5 based on epidemiological and biological evidence including genetic, epigenetic, and molecular mechanisms. The limitations of existing researches and the prospects for the future are also well clarified in this paper to provide insights for future studies.

Exosomal miR-211-5p regulates glucose metabolism, pyroptosis, and immune microenvironment of melanoma through GNA15.

Despite the unprecedented advancement of cancer treatment, the prognosis for patients with metastatic stage of cancer remains poor. The challenge that underlines this clinical dilemma is the complexity of metastasis. The conventional experiment-driven discovery approaches (the "wet lab") yield overly simplified one-to-one mechanistic relationships that are inept of elucidating the complexity of metastasis. Metastasis research also suffers from the knowledge and skill deficiency of the individual investigators. The importance of the present study is the demonstration that the "dry-lab-driven discovery and wet-lab validation" approach can improve the efficiency of studying complex biological behaviors, and can yield more reliable, objective and comprehensive mechanistic findings that are have clinical significance. Specifically, we applied this approach to study the mechanisms that underline the involvement of exosomal miRNAs in transferring the metastatic capability between heterogenous melanoma cancer cells. We show that the highly metastatic melanoma tumor cells (POL) can transfer their metastatic competency to the low-metastatic melanoma tumor cells (OL) by exosomal miR-211-5p. The oncogenic activity of miR-211-5p is mediated by the target gene guanine nucleotide-binding protein subunit alpha-15 (GNA15) through modifying the immune function of the tumor microenvironment extrinsically; as well as through inhibiting pyroptosis and augmenting glycolysis within OL cells intrinsically. In addition, we show that exosomal sorting of miR-211-5p is like selective and is subjected to regulation by a transcriptional feedback loop between miR-211-5p and zinc finger FYVE-type containing 26 (ZFYVE26). Furthermore, the "8-genes pyroptosis Risk model" derived from LASSO regression analysis was verified as an independent prognostic factor for melanoma.

Amorphous silica nanoparticles cause abnormal cytokinesis and multinucleation through dysfunction of the centralspindlin complex and microfilaments.

BACKGROUND: With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), its adverse health effects are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unclear. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation. METHODS: Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study in vitro. RESULTS: In vivo, histopathological results showed that the rate of multinucleation was significantly increased in the liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments aggregation. Following mechanism studies indicated that aSiNPs increased ROS levels. The accumulation of ROS further inhibited the PI3k 110ß/Aurora B pathway, leading to a decrease in the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex by inhibiting the PI3k 110ß/Aurora B pathway. PI3K activator IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster. And ROS inhibitors NAC reduced the ratio of multinucleation, alleviated the PI3k 110ß/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst NAC restored the clustering of the centralspindlin. CONCLUSION: This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. ASiNPs exposure caused microfilaments aggregation and inhibited the PI3k 110ß/Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately resulted in cytokinesis failure and the formation of multinucleation.

Analysis of clinical efficacy and safety of hand-sewn anastomosis for the digestive tract with Da Vinci robot in rectal cancer surgery.

PURPOSE: The study aimed to analyze the clinical efficacy and safety of hand-sewn anastomosis for the digestive tract with Da Vinci robot in rectal cancer surgery. METHODS: A retrospective study was conducted to collect the clinical data from 27 patients who underwent Da Vinci robotic rectal cancer radical surgery in the department of gastrointestinal surgery at the Second Affiliated Hospital of Dalian Medical University from August 2019 to February 2022. All patients received a manual suture for digestive tract reconstruction. After the posterior wall was sutured, the anterior wall was sutured continuously. Finally, a prilling thread was used to sew the junction of the front and rear walls. Perioperative indexes and complications were recorded. RESULTS: All 27 patients successfully underwent the operation. Neither conversion to laparotomy nor perioperative death occurred. The operation time and intraoperative blood loss were 183.6 ± 44.8 min and 54.8 ± 34.4 ml, respectively. A total of 15.3 ± 7.8 lymph nodes were harvested. The pain score 24 h after operation was 1.3 ± 1.3. The time out of bed, the time to exhaust, and the time to eat were 15.6 ± 2.9 h, 2.2 ± 0.8 days, and 2.1 ± 0.6 days, respectively. A total of 4 patients (14.8%) developed complications after the operation. Grade B anastomotic leakage gradually resolved after drainage and antibiotic therapy in 1 case. A patient with grade C anastomotic leakage received a second operation for ileostomy. One patient with postoperative pneumonia recovered after anti-infective treatment. Another patient with intraperitoneal hemorrhage improved after symptomatic treatment with blood transfusion and hemostasis. The postoperative hospitalization time and total hospitalization costs were 8.9 ± 4.4 days and 89,236.1 ± 13,527.9 yuan, respectively. CONCLUSIONS: Manual suture with Da Vinci robotic surgery system is safe and feasible for reconstructing the digestive tract in rectal cancer surgery.

Nomogram for predicting prolonged postoperative ileus after laparoscopic low anterior resection for rectal cancer.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a common complication after colorectal surgery that increases patient discomfort, hospital stay, and financial burden. However, predictive tools to assess the risk of PPOI in patients undergoing laparoscopic low anterior resection have not been developed. Thus, the purpose of this study was to develop a nomogram to predict PPOI after laparoscopic low anterior resection for rectal cancer. METHODS: A total of 548 consecutive patients who underwent laparoscopic low anterior resection for mid-low rectal cancer at a single tertiary medical center were retrospectively enrolled between January 2019 and January 2023. Univariate and multivariate logistic regression analysis was performed to analyze potential predictors of PPOI. The nomogram was constructed using the filtered variables and internally verified by bootstrap resampling. Model performance was evaluated by receiver operating characteristic curve and calibration curve, and the clinical usefulness was evaluated by the decision curve. RESULTS: Among 548 consecutive patients, 72 patients (13.1%) presented with PPOI. Multivariate logistic analysis showed that advantage age, hypoalbuminemia, high surgical difficulty, and postoperative use of opioid analgesic were independent prognostic factors for PPOI. These variables were used to construct the nomogram model to predict PPOI. Internal validation, conducted through bootstrap resampling, confirmed the great discrimination of the nomogram with an area under the curve of 0.738 (95%CI 0.736-0.741). CONCLUSIONS: We created a novel nomogram for predicting PPOI after laparoscopic low anterior resection. This nomogram can assist surgeons in identifying patients at a heightened risk of PPOI.

Association of long-term exposure to ambient air pollutants with cardiac structure and cardiovascular function in Chinese adults.

Epidemiological evidence increasingly suggests that air pollutants are intimately associated with the incidence and mortality of cardiovascular diseases (CVDs). However, studies on the association between chronic exposure to air pollutants and changes in left cardiac function and structure are limited. In our cross-sectional study, 3145 participants were enrolled from 6 provinces to explore the relationship between long-term air pollutants, cardiac structure, and cardiovascular function (e.g., blood lipids, blood pressure and pulse) in Chinese adults. Our study showed that exposure to five pollutants (NO2, O3, PM1, PM2.5 and PM10) was associated with reduced left ventricular systolic function based on EF and SV parameters. These pollutants were also associated with increased pulses, where smaller particle sizes correlated significantly with pulses. Second, except for O3, four pollutants were associated with decreased left ventricular diastolic parameters LVIDd and EDV and increased cardiac structural parameter IVSd. In addition, exposures to NO2, O3 and PM10 were positively correlated with triglycerides in blood lipids. Overall, this study showed that chronic pollutant exposure is strongly associated with impaired left ventricular function in Chinese adults.