Exploring the binding affinity and characteristics of DcitOBP9 in citrus psyllids.

Odorant-binding proteins (OBPs) are crucial in insect olfaction. The most abundant expressed OBP of citrus psyllids, DcitOBP9 encodes 148 amino acids. DcitOBP9 lacks a transmembrane structure and possesses a 17-amino acid signal peptide at the N-terminus. Characterized by the six conserved cysteine sites, DcitOBP9 is classified as the Classical-OBP family. RT-qPCR experiments revealed ubiquitous expression of DcitOBP9 across all developmental stages of the citrus psyllid, with predominant expression in adults antennae. Fluorescence competitive binding assays demonstrated DcitOBP9's strong affinity for ocimene, linalool, dodecanoic acid, and citral, and moderate affinity for dimethyl trisulfide. Additionally, it binds to myrcia, (-)-trans-caryophyllene, (±)-Citronellal, nonanal, and (+)-α-pinene. Among them, ocimene, linalool, and dodecanoic acid were dynamically bound to DcitOBP9, while citral was statically bound to DcitOBP9. Molecular docking simulations with the top five ligands indicated that amino acid residues V92, S72, P128, L91, L75, and A76 are pivotal in the interaction between DcitOBP9 and these odorants. These findings suggest DcitOBP9's involvement in the citrus psyllid's host plant recognition and selection behaviors, thereby laying a foundation for elucidating the potential physiological and biological functions of DcitOBP9 and developing attractants.

Hibiscus manihot L. flower extract induces anticancer activity through modulation of apoptosis and autophagy in A549 cells.

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment. This study revealed that Hibiscus manihot L. flower extract (HML) suppressed the proliferation and migration of A549 cells in a dose and time dependent manner and disrupting cell cycle progression. HML markedly enhanced the accumulation of ROS, stimulated the dissipation of mitochondrial membrane potential (MMP) and that facilitated mitophagy through the loss of mitochondrial function. In addition, HML induced apoptosis by activation of the PTEN-P53 pathway and inhibition of ATG5/7-dependent autophagy induced by PINK1-mediated mitophagy in A549 cells. Moreover, HML exert anticancer effects together with 5-FU through synergistic effect. Taken together, HML may serve as a potential tumor prevention and adjuvant treatment for its functional attributes.

Structure-Guided Design of Ferritin-Platinum Prodrugs for Targeted Therapy of Esophageal Squamous Cell Carcinoma.

Due to its intrinsic tumor-targeting attribute, limited immunogenicity, and cage architecture, ferritin emerges as a highly promising nanocarrier for targeted drug delivery. In the effort to develop ferritin cage-encapsulated cisplatin (CDDP) as a therapeutic agent, we found unexpectedly that the encapsulation led to inactivation of the drug. Guided by the structural information, we deciphered the interactions between ferritin cages and CDDP, and we proposed a potential mechanism responsible for attenuating the antitumor efficacy of CDDP encapsulated within the cage. Six platinum prodrugs were then designed to avoid the inactivation. The antitumor activities of these ferritin-platinum prodrug complexes were then evaluated in cells of esophageal squamous cell carcinoma (ESCC). Compared with free CDDP, the complexes were more effective in delivering and retaining platinum in the cells, leading to increased DNA damage and enhanced cytotoxic action. They also exhibited improved pharmacokinetics and stronger antitumor activities in mice bearing ESCC cell-derived xenografts as well as patient-derived xenografts. The successful encapsulation also illustrates the critical significance of comprehending the interactions between small molecular drugs and ferritin cages for the development of precision-engineered nanocarriers.

ACSS3 regulates the metabolic homeostasis of epithelial cells and alleviates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis. ACSS3 participated in lipid and carbohydrate metabolism. Increased expression of ACSS3 downregulated carnitine palmitoyltransferase 1A (CPT-1A) and resulted in the accumulation of lipid droplets, while enhanced glycolysis which led to an increase in extracellular lactic acid levels in A549 cells. ACSS3 increases the production of succinyl-CoA through propionic acid metabolism, and decreases the generation of acetyl-CoA and ATP in alveolar epithelial cells. Overexpression of Acss3 inhibited the excessive deposition of ECM and attenuated the ground-glass opacity which determined by micro-CT in vivo. In a nutshell, our findings demonstrate that ACSS3 decreased the fatty acid oxidation through CPT1A deficiency and enhanced anaerobic glycolysis, this metabolic reprogramming deactivate the alveolar epithelial cells by lessen mitochondrial fission and fusion, increase of ROS production, suppression of mitophagy, promotion of apoptosis, suggesting that ACSS3 might be potential therapeutic target in pulmonary fibrosis.

Tackling Esophageal Squamous Cell Carcinoma with ITFn-Pt(IV): A Novel Fusion of PD-L1 Blockade, Chemotherapy, and T-cell Activation.

PD-1/PD-L1 blockade immunotherapy has gained approval for the treatment of a diverse range of tumors; however, its efficacy is constrained by the insufficient infiltration of T lymphocytes into the tumor microenvironment, resulting in suboptimal patient responses. Here, a pioneering immunotherapy ferritin nanodrug delivery system denoted as ITFn-Pt(IV) is introduced. This system orchestrates a synergistic fusion of PD-L1 blockade, chemotherapy, and T-cell activation, aiming to augment the efficacy of tumor immunotherapy. Leveraging genetic engineering approach and temperature-regulated channel-based drug loading techniques, the architecture of this intelligent responsive system is refined. It is adept at facilitating the precise release of T-cell activating peptide Tα1 in the tumor milieu, leading to an elevation in T-cell proliferation and activation. The integration of PD-L1 nanobody KN035 ensures targeted engagement with tumor cells and mediates the intracellular delivery of the encapsulated Pt(IV) drugs, culminating in immunogenic cell death and the subsequent dendritic cell maturation. Employing esophageal squamous cell carcinoma (ESCC) as tumor model, the potent antitumor efficacy of ITFn-Pt(IV) is elucidated, underscored by augmented T-cell infiltration devoid of systemic adverse effects. These findings accentuate the potential of ITFn-Pt(IV) for ESCC treatment and its applicability to other malignancies resistant to established PD-1/PD-L1 blockade therapies.

Cancer cell membrane fused liposomal platinum(IV) prodrugs overcome cisplatin resistance in esophageal squamous cell carcinoma chemotherapy.

Esophageal squamous cell carcinoma (ESCC) remains a major health challenge, with cisplatin (CDDP) being the primary chemotherapy drug, albeit accompanied by resistance development over time. This study introduces a novel platinum drug delivery system, EMLipoPt(IV), tailored to enhance platinum uptake and diminish its inactivation, providing a solution to CDDP resistance in ESCC. By synthesizing a fusion of the ESCC cell membrane with liposomal Pt(IV) prodrugs, we integrated the tumor-targeting capacity of the ESCC membrane with the inactivation resistance of Pt(IV) prodrugs. In vivo and in vitro evaluations illustrated EMLipoPt(IV)'s robustness against inactivating agents, superior tumor-targeting capacity, and remarkable ability to suppress CDDP-resistant tumor progression. Importantly, the biosafety profile of EMLipoPt(IV) surpassed existing treatments, offering a prolonged survival rate in animal models. Collectively, this work not only presents a pioneering approach in ESCC chemotherapy but also provides a blueprint for combating drug resistance in other cancers, emphasizing the broader potential for tailored drug delivery systems.

Genome-wide association analysis unveils candidate genes and loci associated with aplasia cutis congenita in pigs.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare genetic disorder characterized by the localized or widespread absence of skin in humans and animals. Individuals with ACC may experience developmental abnormalities in the skeletal and muscular systems, as well as potential complications. Localized and isolated cases of ACC can be treated through surgical and medical interventions, while extensive cases of ACC may result in neonatal mortality. The presence of ACC in pigs has implications for animal welfare. It contributes to an elevated mortality rate among piglets at birth, leading to substantial economic losses in the pig farming industry. In order to elucidate candidate genetic loci associated with ACC, we performed a Genome-Wide Association Study analysis on 216 Duroc pigs. The primary goal of this study was to identify candidate genes that associated with ACC. RESULTS: This study identified nine significant SNPs associated with ACC. Further analysis revealed the presence of two quantitative trait loci, 483 kb (5:18,196,971-18,680,098) on SSC 5 and 159 kb (13:20,713,440-207294431 bp) on SSC13. By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR. CONCLUSIONS: The results of this study further elucidate the potential mechanisms underlying and genetic architecture of ACC and identify reliable candidate genes. These results lay the foundation for treating and understanding ACC in humans.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia.

Introduction: Acute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m6A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance. Methods: To investigate the m6A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m6A modification activity of cells in AML patients based on 23 m6A modification enzymes and further integrated with bulk RNA-seq data. Results: We found that m6A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m6A modification status in leukemia cells, while active m6A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m6A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by RUNX1 mutation and KMT2A copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of IGF2BP3 and FMR1, and low expression level of ELAVL1 and YTHDF2. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings suggest that m6A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.

Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional alveolar type II epithelial cells into alveolar type I epithelial cells and inhibiting fibroblast activation and extracellular matrix production potentially by regulation of Nr2f2. In addition, T3 regulated the crosstalk of macrophages with fibroblasts, and the Pros1-Axl signaling axis significantly facilitated the attenuation of fibrosis. The findings demonstrate that administration of a thyroid hormone promotes alveolar regeneration and resolves fibrosis mainly by regulation of the cellular state and cell-cell communication of alveolar epithelial cells, macrophages, and fibroblasts in mouse lungs in comprehensive ways.

Serum Proteomics Identifies Biomarkers Associated With the Pathogenesis of Idiopathic Pulmonary Fibrosis.

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684-0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.

Artificial neural network identified the significant genes to distinguish Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that causes irreversible damage to lung tissue characterized by excessive deposition of extracellular matrix (ECM) and remodeling of lung parenchyma. The current diagnosis of IPF is complex and usually completed by a multidisciplinary team including clinicians, radiologists and pathologists they work together and make decision for an effective treatment, it is imperative to introduce novel practical methods for IPF diagnosis. This study provided a new diagnostic model of idiopathic pulmonary fibrosis based on machine learning. Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified based on the differentially expressed genes in IPF patients compare to healthy subjects through a random forest classifier with the existing gene expression databases. An artificial neural network model was constructed for IPF diagnosis based these genes, and this model was validated by the distinctive public datasets with a satisfactory diagnostic accuracy. These six genes identified were significant correlated with lung function, and among them, CDH3 and DIO2 were further determined to be significantly associated with the survival. Putting together, artificial neural network model identified the significant genes to distinguish idiopathic pulmonary fibrosis from healthy people and it is potential for molecular diagnosis of IPF.

Protective Effects of Hippophae rhamnoides L. Phenylpropanoids on Doxorubicin-Induced Cardiotoxicity in Zebrafish.

Hippophae rhamnoides L. is a deciduous shrub that contains many unique bioactive substances. This sea buckthorn possesses anticancer, antioxidant, anti-inflammatory, and cardiovascular protective properties. Herein, the effects of phenylpropyl compounds extracted from H. rhamnoides L. on doxorubicin (Dox)-induced cardiotoxicity were evaluated in zebrafish. Cardiac injury in zebrafish was induced using 35 µM Dox for 96 h, and 30 µM phenylpropanoid compounds were used as the protective treatment. The cardioprotective effects and mechanisms of the four phenylpropanoids were investigated using microscopy, behavioral analysis, acridine orange staining, western blotting, flow cytometry, and real-time quantitative polymerase chain reaction. The extracted phenylpropanoids could significantly relieve Dox-induced cardiac injury in zebrafish and inhibit cardiomyocyte apoptosis. The mechanisms of action were mainly related to the stability of mitochondrial biogenesis and function maintained by phenylpropanoids in zebrafish. To our knowledge, this is the first report on the protective effect of sea buckthorn against myocardial injury in zebrafish. Our findings provide support for the further research and development of sea buckthorn and its components.

Long-term nutritional status after total gastrectomy was comparable to proximal gastrectomy but with much less reflux esophagitis and anastomotic stenosis.

Aim: To compare the long-term nutritional status, reflux esophagitis and anastomotic stenosis, between total gastrectomy (TG) and proximal gastrectomy (PG). Methods: Patients who underwent PG or TG in this single institution between January 2014 and December 2016 were included in this study. The inclusion and exclusion criteria were defined. One-to-one propensity score matching (PSM) by the demographic and pathological characteristics was performed to compare the long-term outcomes between the two groups. The primary endpoint was long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes. Results: Totally 460 patients received PG or TG in our institution for the treatment between January 2014 and December 2016 and according to the inclusion and exclusion criteria 226 cases were included in this study finally. There was no significant difference as to nutritional status in the end of first 5 years after PG or TG. While reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group (54.4% versus 26.8%, p < 0.001; 14.9% versus 4.5%, p=0.015; respectively). Overall survival rates were similar between the two groups after PSM (5-year survival rates: 65.4% versus 61.5% in the PG and TG groups, respectively; p = 0.54). The rate of carcinoma of remnant stomach after PG was 3.5% in this group of patients. Conclusions: TG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG.

Hyperthermic intraperitoneal chemotherapy for patients with gastric cancer based on laboratory tests is safe: a single Chinese center analysis.

PURPOSE: About 15%-40% of gastric cancer patients have peritoneal metastasis, which leads to poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is considered to be an effective treatment for these patients. This study evaluated the efficacy and safety of HIPEC in patients with gastric cancer diagnosed from laboratory tests. METHODS: The clinical and pathological data of 63 patients with gastric cancer who underwent HIPEC in 2017-2021 were prospectively recorded. Fifty-five patients underwent cytoreductive surgery + HIPEC, and eight patients received HIPEC alone. The factors associated with HIPEC safety and efficacy were analyzed. The primary endpoint was overall survival. RESULTS: The average patient age was 54.84 years and 68.3% of patients were male. Moreover, 79.4% of patients had a peritoneal carcinoma index (PCI) score of ≤ 7 and 61.9% had a completeness of cytoreduction score of 0. Because of peritoneal metastasis, 29 patients (46.03%) were classified as stage IV. Laboratory tests showed no differences in pre-HIPEC blood test results compared to post-HIPEC results after removing the effects of surgery. HIPEC treatment did not cause obvious liver or kidney damage. Serum calcium levels decreased significantly after HIPEC (P = 0.0018). The Karnofsky performance status (KPS) score correlated with the patient's physical function and improved after HIPEC (P = 0.0045). In coagulation tests, FDP (P < 0.0001) and D-dimer (P < 0.0001) levels increased significantly and CA242 (P = 0.0159), CA724 (P < 0.0001), and CEA (P < 0.0014) levels decreased significantly after HIPEC. Completeness of cytoreduction score was an independent prognostic factor. HIPEC did not show a survival benefit in patients with gastric cancer (P = 0.5505). CONCLUSION: HIPEC is a safe treatment for patients with gastric cancer with peritoneal metastasis based on the laboratory tests. However, the efficacy of this treatment on gastric-derived peritoneal metastases requires further confirmation.

Dynamic monitoring revealed a slightly prolonged waiting time for total gastrectomy during the COVID-19 pandemic without increasing the short-term complications.

We aimed to determine the pattern of delay and its effect on the short-term outcomes of total gastrectomy before and during the coronavirus disease 2019 (COVID-19) pandemic. Overlaid line graphs were used to visualize the dynamic changes in the severity of the pandemic, number of gastric cancer patients, and waiting time for a total gastrectomy. We observed a slightly longer waiting time during the pandemic (median: 28.00 days, interquartile range: 22.00-34.75) than before the pandemic (median: 25.00 days, interquartile range: 18.00-34.00; p = 0.0071). Moreover, we study the effect of delayed surgery (waiting time > 30 days) on short-term outcomes using postoperative complications, extreme value of laboratory results, and postoperative stay. In patients who had longer waiting times, we did not observe worse short-term complication rates (grade II-IV: 15% vs. 19%, p = 0.27; grade III-IV: 7.3% vs. 9.2%, p = 0.51, the short waiting group vs. the prolonged waiting group) or a higher risk of a longer POD (univariable: OR 1.09, 95% CI 0.80-1.49, p = 0.59; multivariable: OR 1.10, 95% CI 0.78-1.55, p = 0.59). Patients in the short waiting group, rather than in the delayed surgery group, had an increased risk of bleeding in analyses of laboratory results (plasma prothrombin activity, hemoglobin, and hematocrit). A slightly prolonged preoperative waiting time during COVID-19 pandemic might not influence the short-term outcomes of patients who underwent total gastrectomy.

Discovery of N-benzylarylamide derivatives as novel tubulin polymerization inhibitors capable of activating the Hippo pathway.

Novel N-benzylarylamide saderivatives were designed and synthesized, and their antiproliferative activities were explored. Some of 51 target compounds exhibited potent inhibitory activities against MGC-803, HCT-116 and KYSE450 cells with IC50 values in two-digit nanomolar. Compound I-33 (MY-875) displayed the most potent antiproliferative activities against MGC-803, HCT-116 and KYSE450 cells (IC50 = 0.027, 0.055 and 0.067 µM, respectively) and possessed IC50 values ranging from 0.025 to 0.094 µM against other 11 cancer cell lines. Further mechanism studies indicated that compound I-33 (MY-875) inhibited tubulin polymerization (IC50 = 0.92 µM) by targeting the colchicine bingding site of tubulin. Compound I-33 (MY-875) disrupted the construction of the microtubule networks and affected the mitosis in MGC-803 and SGC-7901 cells. In addition, although it acted as a colchicine binding site inhibitor, compound I-33 (MY-875) also activated the Hippo pathway to promote the phosphorylation status of MST and LATS, resulting in the YAP degradation in MGC-803 and SGC-7901 cells. Due to the degradation of YAP, the expression levels of TAZ and Axl decreased. Because of the dual actions on colchicine binding site and Hippo pathway, compound I-33 (MY-875) dose-dependently inhibited cell colony formatting ability, arrested cells at the G2/M phase and induced cells apoptosis in MGC-803 and SGC-7901 cells. Moreover, compound I-33 (MY-875) could regulate the levels of cell cycle and apoptosis regulatory proteins in MGC-803 and SGC-7901 cells. Furthermore, molecular docking analysis suggested that the hydrogen bond and hydrophobic interactions made compound I-33 (MY-875) well bind into the colchicine binding site of tubulin. Collectively, compound I-33 (MY-875) is a novel anti-gastric cancer agent and deserves to be further investigated for cancer therapy by targeting the colchicine binding site of tubulin and activating the Hippo pathway.

Platelet is the early predictor of bronchopulmonary dysplasia in very premature infants: an observational cohort study.

BACKGROUND: A previous study showed that the lungs are involved in the biogenesis of platelets (PLTs). Thus, the present study aimed to investigate the association between bronchopulmonary dysplasia (BPD), a chronic lung disease, and PLT parameters in very premature infants. METHODS: The study subjects were premature infants with a gestational age of ≤ 30 weeks and birth weight of ≤ 1500 g in a preterm birth cohort study recruited between January 1, 2015, and August 31, 2019. BPD was defined as the need for oxygen supplementation more than 28 days after birth. The PLT count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) level were compared between BPD and non-BPD infants. A generalized estimating equation model was used to adjust for confounding factors. A forward stepwise logistic regression model was used to calculate the adjusted odds ratio (OR) for thrombocytopenia in the BPD group. Receiver operating characteristic curve analysis was performed to assess the predictive value of PLT count combined with gestational age (GA) and birth weight (BW) for BPD. RESULTS: The final study subjects were 134 very premature infants, namely, 64 infants with BPD and 70 infants without BPD. The BPD infants had lower PLT counts (F = 4.44, P = 0.03) and PCT levels (F = 12.54, P = 0.00) than the non-BPD infants. However, the MPV (F = 14.25, P = 0.00) and PDW (F = 15.04, P = 0.00) were higher in the BPD group. After adjusting for potential confounding factors, the BPD infants had a higher risk of thrombocytopenia than the non-BPD infants (adjusted aOR 2.88, 95% CI 1.01-8.15), and the risk of BPD was increased in very premature infants with a PLT count ≤ 177*109/L (OR 4.74, 95% CI 1.93-11.62) at the end of the second week. In the multivariate predictive model, it was showed that the AUC area (0.85), sensitivity (0.88), specificity (0.70) and Youden index (0.58) are improved using PLT counts ≤ 177*109/L combined with GA and BW. CONCLUSIONS: Abnormal PLT parameters were observed in BPD infants, and a PLT count ≤ 177*109/L was a potential risk factor for the development of BPD in very premature infants.

Discovery of novel indole derivatives that inhibit NEDDylation and MAPK pathways against gastric cancer MGC803 cells.

A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 µM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells.

Progress of tubulin polymerization activity detection methods.

Tubulin, an important target in tumor therapy, is one of the hotspots in the field of antineoplastic drugs in recent years, and it is of great significance to design and screen new inhibitors for this target. Natural products and chemical synthetic drugs are the main sources of tubulin inhibitors. However, due to the variety of compound structure types, it has always been difficult for researchers to screen out polymerization inhibitors with simple operation, high efficiency and low cost. A large number of articles have reported the screening methods of tubulin inhibitors and their biological activity. In this article, the biological activity detection methods of tubulin polymerization inhibitors are reviewed. Thus, it provides a theoretical basis for the further study of tubulin polymerization inhibitors and the selection of methods for tubulin inhibitors.

Ras/Raf/MEK/ERK pathway axis mediated neurotoxicity induced by high-risk pesticide residue-Avermectin.

Pesticide residues have become a healthy threaten of human beings. Among the pesticides, many of them have neurotoxicity. Extracellular Regulated Protein Kinases (ERK) pathway is an important signaling pathway that regulates a variety of downstream progress. In this work, peach (PRUNUS persica) and cherry (PRUNUS cerasus) were sampled from over 300 plantations in China and assessed for the residue risk. In mechanism studies, high-risk pesticide Avermectin showed a high activity inhibiting three neurotoxicity models, SH-SY5Y, PC-12 and SK-N-SH cells. At protein levels, ERK pathway proteins and their downstream proteins were obviously down-regulated. Moreover, the effects of low-dose Avermectin can be accumulated at protein levels in the low-dose long-term chronic toxicology detection.