Evaluation of emergency drills effectiveness by center of disease prevention and control staff in Heilongjiang Province, China: an empirical study using the logistic-ISM model.

Introduction: Emergency drills are critical practices that can improve the preparedness for crisis situations. This study aims to comprehend the evaluation of emergency drill effectiveness by the staff at the Centers for Disease Control and Prevention (CDC) in Heilongjiang Province, China. It identifies potential factors that could influence the personnel's appraisal of outcomes throughout the emergency drill procedure. Methods: A cross-sectional survey was conducted among public health professionals from various CDCs in Heilongjiang, a northeastern Chinese province. The binary logistic regression analysis identified the factors associated with the CDC staff's assessment of emergency drill efficacy, while the Interpretative Structural Modeling (ISM) elucidated the hierarchical structure among the influencing factors. Results: 53.3% (95% CI = 50.6-55.4) of participants perceived the emergency drills' effectiveness as low. Binary logistic regression analysis revealed that the following adverse factors associated with the emergency drills increased the risk of a lower evaluation: lack of equipment and poor facilities (OR = 2.324, 95% CI = 1.884-2.867), poor training quality (OR = 1.765, 95% CI = 1.445-2.115), low leadership focus (OR = 1.585, 95% CI = 1.275-1.971), insufficient training frequency (OR = 1.539, 95% CI = 1.258-1.882), low skill in designing emergency drill plans (OR = 1.494, 95% CI = 1.180-1.890), lack of funding (OR = 1.407, 95% CI = 1.111-1.781), and poor coordination between departments (OR = 1.335, 95% CI = 1.085-1.641). The ISM revealed the hierarchical relationship of the influential factors, which were classified into three levels: Surface, Middle and Bottom. The Surface Level factors were training frequency, training quality, leaders' focus, and inter-departmental coordination. The Middle Level factors were equipment availability and skill in designing emergency drill plans. The Bottom Level factor was funding guarantee. Discussion: This survey revealed that over half of the CDC staff rated the effectiveness of public health emergency drills as low. The Logistic-ISM Model results indicated that the evaluation of drill effectiveness was negatively influenced by insufficient facility and equipment support, financial constraints, lack of departmental coordination, and inadequate leadership attention. Among these factors, funding guarantee was the most fundamental one. Therefore, this calls for strategic decisions to increase funding for equipment, leadership training support, and effective emergency coordination.

IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development.

BACKGROUND: IGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended. METHODS: The mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays. RESULTS: We observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses. CONCLUSIONS: Our present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer.

CT-Diagnosed Non-Alcoholic Fatty Liver Disease as a Risk Predictor of Symptomatic Carotid Plaque and Cerebrovascular Symptoms.

We aimed to test whether computed tomography (CT)-diagnosed Non-Alcoholic Fatty Liver Disease (NAFLD) is a risk factor for cerebrovascular symptoms in patients with suspected atherosclerotic disease. A total of 550 patients (mean age 65.2 ± 8.8 years, 370 males) with carotid plaques who underwent carotid computed tomographic angiography (CTA) and unenhanced abdominal CT were retrospectively analyzed. NAFLD was diagnosed by abdominal CT. Carotid CTA assessed the presence of carotid artery stenosis or plaque. The relationship between NAFLD and cerebrovascular symptoms was analyzed using generalized estimating equations and receiver operating characteristic (ROC) analysis. The prevalence of NAFLD was significantly higher in symptomatic patients (76.5 vs 9.8%; P < .001). After adjusting for several confounding factors (e.g., hypertension and hyperlipidemia), univariate and multivariate logic regression analysis revealed that NAFLD was still strongly associated with cerebrovascular symptoms (odds ratio, 22.81; 95% CI 13.03-39.93; P < .001). ROC analysis showed that the area under the curve for discriminating symptomatic and asymptomatic plaques using NAFLD measurements was 0.833, with a sensitivity of 76.5% and a specificity of 90.2%. NAFLD is strongly associated with an increased risk of cerebrovascular symptoms. It may be an important predictor of symptomatic carotid plaque and cerebrovascular symptoms.

A finite element analysis of stress distribution with various directions of intermaxillary fixation using orthodontic mini-implants and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy.

OBJECTIVE: This finite element analysis (FEA) aimed to assess the stress distribution in the mandible and fixation system with various directions of the intermaxillary fixation (IMF) using mini-implants (MIs) and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy (BSSRO). MATERIALS AND METHODS: A total of nine mandibular advancement models were set according to the position of the MIs (1.6 mm in diameter, 8 mm in length) and direction of the IMF elastics (1/4 inch, 5 oz). Major and minor principal stresses in the cortical and cancellous bones, von Mises stresses in the fixation system (miniplate and monocortical screws), and bending angles of the miniplate were analysed. RESULTS: Compressive and tensile stress distributions in the mandible and von Mises stress distributions in the fixation system were greater in models with a Class III IMF elastic direction and a higher IMF elastic force than in models with a Class II IMF elastic direction and a lower IMF elastic force. The bending angle of the miniplate was negligible. CONCLUSIONS: Stress distributions in the bone and fixation system varied depending on the direction, amount of force, and position of IMF elastics and MIs. Conclusively, IMF elastics in the Class II direction with minimal load in the area close to the osteotomy site should be recommended.

Interdisciplinary treatment of mutilated dentition and transverse maxillary deficiency with microimplant-assisted rapid palatal expansion, microimplants, and dental implants.

OBJECTIVE: This case report demonstrates an interdisciplinary approach to treat a 26-year-old male patient with hyperdivergent Class II skeletal pattern, maxillary transverse deficiency, slight anterior open bite, and multiple hopeless teeth with root rests. CLINICAL CONSIDERATIONS: An interdisciplinary treatment was required for oral hygiene improvement, caries treatment, extraction of residual roots and hopeless teeth, maxillary expansion using microimplant-assisted rapid palatal expansion, improvement of skeletal and dental relationship using orthodontic microimplants, and prosthetic restorations with the aid of dental implants. CONCLUSION: Consequently, esthetic and functional occlusal rehabilitation was achieved. CLINICAL SIGNIFICANCE: Hyperdivergent Class II facial and skeletal patterns with multiple missing teeth can be effectively treated using orthodontic skeletal anchorage. In young adults, the transverse discrepancy can be resolved using MARPE, which is also useful for improving the sagittal and vertical relationships. In the case of multiple missing teeth, orthodontic treatment can provide the proper space to facilitate dental implants to achieve optimal esthetics and function.

Effects of Datura stramonium L. Invasion into Different Habitats on Native Plant Functional Traits and Soil Carbon, Nitrogen and Phosphorus Stoichiometric Characteristics.

Datura stramonium is an invasive herb of the family Solanaceae from Mexico and has been invading seriously in China. The effects of invasive plants on the functional traits of native plants and the stoichiometric characteristics of soil carbon, nitrogen and phosphorus in different habitats were explored by taking the invasive plant D. stramonium and coexisting native plants as the research object. The species, quantity and height of plants in sample plots in farmland, wasteland and roadside habitats were investigated and the specific leaf area (SLA), leaf carbon content (C), nitrogen content (N), carbon-to-nitrogen ratio (C:N), construction cost (CCmass) and stoichiometric characteristics of soil carbon (C), nitrogen (N) and phosphorus (P) were analyzed. The results showed that compared with the noninvaded area, the species and quantity of native plants decreased in the invaded area, and SLA and leaf N showed a decreasing trend. The plant height of native plants in the invaded area of the farmland and wasteland decreased by 23.19% and 15.26%, respectively, while the height of native plants along the roadside increased by 95.91%. The leaf C:N ratio of native plants in the invaded area along the roadside significantly increased by 54.07%. The plant height and leaf N of D. stramonium in the three habitats were higher than those of the native plants. The soil N in the invaded area of the three habitats increased, with the soil N in the farmland increasing by 21.05%, in the wasteland increasing by 9.82% and along the roadside significantly increasing by 46.85%. The soil carbon-to-phosphorus ratio (C:P) in the three habitats showed an increasing trend. The soil C:P ratio in the farmland increased by 62.45%, in the wasteland it increased by 11.91% and along the roadside it significantly increased by 71.14%. These results showed that invasion by D. stramonium has a great effect on the local ecosystem, and it has a high ability to capture resources. D. stramonium can improve its own competitiveness by enhancing invasiveness by changing the functional traits of native plants and the stoichiometric characteristics of soil C, N and P, which may be the reason for its invasive success.

Differential clinical and CT imaging features of pneumonic-type primary pulmonary lymphoma and pneumonia: a retrospective multicentre observational study.

INTRODUCTION: Pneumonic-type primary pulmonary lymphoma (PPL) is often misdiagnosed as pneumonia in clinical practice. However, this disease requires different treatments, which calls for a correct diagnosis. MATERIALS AND METHODS: A total of 227 patients with pneumonic-type PPL (n=72) and pneumonia (n=155) from 7 institutions were retrospectively enrolled between January 2017 and January 2022. Clinical features (age, sex, cough, sputum, fever, haemoptysis, chest pain, smoking, weight loss and laboratory results (haemoglobin, white blood cell count, C reactive protein level and erythrocyte sedimentation rate)) and CT imaging characteristics (air bronchogram, bronchiectasis, halo sign, pleural traction, pleural effusion, lymphadenopathy, lesion maximum diameter and CT attenuation value) were analysed. Receiver operating characteristic curve analysis was performed for model construction based on independent predictors in identifying pneumonic-type PPL. In addition, we used a calibration curve and decision curve analysis to estimate the diagnostic efficiency of the model. RESULTS: The patients with pneumonia showed a higher prevalence of sputum, fever, leucocytosis and elevation of C reactive protein level than those with pneumonic-type PPL (p=0.002, p<0.001, p=0.011 and p<0.001, respectively). Bronchiectasis, halo sign and higher CT attenuation value were more frequently present in pneumonic-type PPL than in pneumonia (all p<0.001). Pleural effusion was more commonly observed in patients with pneumonia than those with pneumonic-type PPL (p<0.001). Also, sputum, fever, elevation of C reactive protein level, halo sign, bronchiectasis, pleural effusion and CT attenuation value were the independent predictors of the presence of pneumonic-type PPL with an area under the curve value of 0.908 (95% CI, 0.863 to 0.942). CONCLUSION: Pneumonic-type PPL and pneumonia have different clinical and imaging features. These differential features could be beneficial in guiding early diagnosis and subsequent initiation of therapy.

Tilted implants for implant-supported fixed hybrid prostheses: retrospective review.

Objectives: This review assessed the performance of implant-supported fixed hybrid prostheses in 21 patients who received a total of 137 implants between 2003 and 2010. The implants were evaluated for marginal bone resorption, complications, success rate, and survival rate based on their vertical angularity, type of bone graft, and measured implant stability. Materials and Methods: One-way ANOVA and chi-square tests were used to analyze the relationships among long-term evaluation factors and these variables. The mean initial bone resorption in the implant group with a vertical angle of more than 20° was 0.33 mm and mean final bone resorption was 0.76 mm. In contrast, the mean initial bone resorption in the implant group with a vertical angle of less than 10° was 1.19 mm and mean final bone resorption was 2.17 mm. Results: The results showed that mean bone resorption decreased with an increase in the vertical placement angle of the implants used in fixed hybrid prostheses, as well as in the group without additional bone grafts and those with high implant stability. The success rate of implants placed after bone grafting was found to be higher than those placed simultaneously. Conclusion: These results suggest that implant-supported fixed hybrid prostheses may be an effective treatment option for edentulous patients, and intentionally placing implants with high angularity may improve outcomes.

Monocyte-derived Kupffer cells dominate in the Kupffer cell pool during liver injury.

Healthy Kupffer cell (KC) pool is dominated by embryonic KCs (EmKCs), preserving liver homeostasis. How the KC pool varies upon injury remains unclear. Using chimeric mice with bone marrow (BM) cells labeled with enhanced green fluorescent protein, we identify that BM monocyte-derived KCs (MoKCs) become dominant in cholestatic- or toxic-injured livers via immunofluorescence and mass cytometry. Single-cell RNA sequencing (scRNA-seq) unveils the enhanced proliferative, anti-apoptotic properties and repair potential of MoKCs compared with EmKCs, which are confirmed in vivo and ex vivo through flow cytometry, qPCR, Cell Counting Kit-8, and immunofluorescence. Furthermore, compared with EmKC-dominated livers, MoKC-dominated livers exhibit less functional damage, necrosis, and fibrosis under damage, as tested by serum alanine aminotransferase activity detection, H&E and Sirius red staining, qPCR, and western blot. Collectively, we highlight that MoKCs dominate the KC pool in injured livers and show enhanced proliferative and anti-apoptotic properties while also promoting repair and attenuating fibrosis.

Assessing Abdominal Aortic Aneurysm Progression by Using Perivascular Adipose Tissue Attenuation on Computed Tomography Angiography.

OBJECTIVE: Recent studies have highlighted the active and potential role of perivascular adipose tissue (PVAT) in atherosclerosis and aneurysm progression, respectively. This study explored the link between PVAT attenuation and abdominal aortic aneurysm (AAA) progression using computed tomography angiography (CTA). MATERIALS AND METHODS: This multicenter retrospective study analyzed patients with AAA who underwent CTA at baseline and follow-up between March 2015 and July 2022. The following parameters were obtained: maximum diameter and total volume of the AAA, presence or absence of intraluminal thrombus (ILT), maximum diameter and volume of the ILT, and PVAT attenuation of the aortic aneurysm at baseline CTA. PVAT attenuation was divided into high (> -73.4 Hounsfield units [HU]) and low (≤ -73.4 HU). Patients who had or did not have AAA progression during the follow-up, defined as an increase in the aneurysm volume > 10 mL from baseline, were identified. Kaplan-Meier and multivariable Cox regression analyses were used to investigate the association between PVAT attenuation and AAA progression. RESULTS: Our study included 167 participants (148 males; median age: 70.0 years; interquartile range: 63.0-76.0 years), of which 145 (86.8%) were diagnosed with AAA accompanied by ILT. Over a median period of 11.3 months (range: 6.0-85.0 months), AAA progression was observed in 67 patients (40.1%). Multivariable Cox regression analysis indicated that high baseline PVAT attenuation (adjusted hazard ratio [aHR] = 2.23; 95% confidence interval [CI], 1.16-4.32; P = 0.017) was independently associated with AAA progression. This association was demonstrated within the patients of AAA with ILT subcohort, where a high baseline PVAT attenuation (aHR = 2.23; 95% CI, 1.08-4.60; P = 0.030) was consistently independently associated with AAA progression. CONCLUSION: Elevated PVAT attenuation is independently associated with AAA progression, including patients of AAA with ILT, suggesting the potential of PVAT attenuation as a predictive imaging marker for AAA expansion.

The optimal oxytocin infusion rate for preventing uterine atony during cesarean delivery in elderly parturients with prior history of cesarean delivery.

Background: An estimate of 90% effective dose (ED90) of oxytocin infusion has already been proved effective in non-laboring parturients. However, the requirements of oxytocin for elderly parturients with prior history of cesarean delivery (CD) may be higher. The aim of this study was to find the optimum oxytocin infusion rate for preventing uterine atony during CD in elderly parturients with prior history of CD. Method: We performed a randomized, double-blinded study in 120 healthy elderly parturients with prior history of CD scheduled for elective CD under combined spinal-epidural (CSE) anesthesia. Participants were treated with oxytocin infusion randomly at the rates of 0, 4, 8, 12, 16, or 20 IU h-1 after the delivery of infants. Following oxytocin administration, a blinded obstetrician evaluated the uterine tone (UT), verbally describing it using numerical scales (0-10: 0, no UT; 10, optimal UT) as either adequate or inadequate at the time intervals of 3, 6, and 9 min. Maternal adverse effects, requirements for additional uterotonic agents, delivery-placenta delivery time (PD), and estimated blood loss (EBL) were recorded. Results: The 50% effective dose (ED50) and 90% effective dose (ED90) of oxytocin infusion were 14.6 IU h-1 (95% confidence interval 12.0-18.4 IU h-1) and 27.7 IU h-1 (95% confidence interval 22.5-39.4 IU h-1), respectively. As the rate of infusion was increased in parturients, the rescue oxytocin dose and delivery-PD time were decreased. Parturients who received 0 IU h-1 oxytocin at 3, 6, and 9 min obtained lower UT scores than those who received 16 and 20 IU h-1 oxytocin (p < 0.05, respectively). No significant differences were observed among groups in EBL and maternal adverse effects. Conclusion: The infusion rate of oxytocin at 14.57 and 27.74 IU h-1 produces adequate UT in 50% and 90% of elderly parturients with prior history of CD, respectively. An oxytocin infusion rate of 27.7 IU h-1 is suggested to be the optimal dose for preventing uterine atony during CD in elderly parturients with prior history of cesarean delivery. Clinical Trial Registration: [https://www.chictr.org.cn/bin/project/edit?pid=62489], Identifier: [ChiCTR2000038891].

The mechanisms of minocycline in alleviating ischemic stroke damage and cerebral ischemia-reperfusion injury.

Stroke is a group of diseases resulting from cerebral vascular rupture or obstruction and subsequent brain blood circulation disorder, leading to rapid neurological deficits. Ischemic stroke accounts for the majority of all stroke cases. The current treatments for ischemic stroke mainly include t-PA thrombolytic therapy and surgical thrombectomy. However, these interventions aimed at recanalizing cerebral vessels can paradoxically lead to ischemia-reperfusion injury, which exacerbates the severity of brain damage. Minocycline, a semi-synthetic tetracycline antibiotic, has been shown to possess a wide range of neuroprotective effects independent of its antibacterial activity. Here we summarize the mechanisms underlying the protective effects of minocycline against cerebral ischemia-reperfusion injury based on the pathogenesis of cerebral ischemia-reperfusion injury, including its modulation of oxidative stress, inflammatory response, excitotoxicity, programmed cell death and blood-brain barrier injury, and also introduce the role of minocycline in alleviating stroke-related complications, in order to provide a theoretical basis for the clinical application of minocycline in cerebral ischemia-reperfusion injury.

Extracellular Vesicles Derived circSH3PXD2A Inhibits Chemoresistance of Small Cell Lung Cancer by miR-375-3p/YAP1.

Introduction: Small cell lung cancer (SCLC) is a subtype of lung cancer with high malignancy and poor prognosis. Rapid acquisition of chemoresistance is one of the main reasons leading to clinical treatment failure of SCLC. Studies have indicated that circRNAs participate in multiple processes of tumor progression, including chemoresistance. However, the molecular mechanisms of circRNAs driving the chemoresistance of SCLC are not well specified. Methods: The differentially expressed circRNAs were screened by transcriptome sequencing of chemoresistant and chemosensitive SCLC cells. The EVs of SCLC cells were isolated and identified by ultracentrifugation, Western blotting, transmission electron microscopy, nanoparticle tracking analysis and EVs uptake assays. The expression levels of circSH3PXD2A in serum and EVs of SCLC patients and healthy individuals were detected by qRT‒PCR. The characteristics of circSH3PXD2A were detected by Sanger sequencing, RNase R assay, nuclear-cytoplasmic fraction assay, and fluorescence in situ hybridization assay. The mechanisms of circSH3PXD2A inhibiting SCLC progression were studied by bioinformatics analysis, chemoresistance assay, proliferation assay, apoptosis assay, transwell assay, pull-down assay, luciferase reporting assay, and mouse xenograft assay. Results: It was identified that the circSH3PXD2A was a prominently downregulated circRNA in chemoresistant SCLC cells. The expression level of circSH3PXD2A in EVs of SCLC patients was negatively associated with chemoresistance, and the combination of EVs-derived circSH3PXD2A and serum ProGRP (Progastrin-releasing peptide) levels had better indications for DDP-resistant SCLC patients. CircSH3PXD2A inhibited the chemoresistance, proliferation, migration, and invasion of SCLC cells through miR-375-3p/YAP1 axis in vivo and in vitro. SCLC cells cocultured with EVs secreted by circSH3PXD2A-overexpressing cells exhibited decreased chemoresistance and cell proliferation. Conclusion: Our results manifest that EVs-derived circSH3PXD2A inhibits the chemoresistance of SCLC through miR-375-3p/YAP1 axis. Moreover, EVs-derived circSH3PXD2A may serve as a predictive biomarker for DDP-resistant SCLC patients.

Single-cell RNA seq identifies Plg-RKT-PLG as signals inducing phenotypic transformation of scar-associated macrophage in liver fibrosis.

Hepatic macrophages play a central role in liver fibrosis. Scar-associated macrophages (SAMs), a recently identified subgroup of macrophages, play an important role in this process. However, the mechanism by which SAMs transform during liver fibrosis is still unclear. In this study, we aimed to characterize SAMs and elucidate the underlying mechanism of SAM transformation. Bile duct ligation (BDL) and carbon tetrachloride (CCl4) were used to induce mouse liver fibrosis. Non-parenchymal cells were isolated from normal/fibrotic livers and were analyzed using single cell RNA sequencing (scRNA-seq) or mass cytometry (CyTOF). The glucan-encapsulated siRNA particles (siRNA-GeRPs) was employed to perform macrophage selective gene knockdown. The results of scRNA-seq and CyTOF revealed that SAMs, which derived from bone marrow-derived macrophages (BMMs), accumulated in mouse fibrotic livers. Further analysis showed that SAMs highly expressed genes related to fibrosis, indicating the pro-fibrotic functions of SAMs. Moreover, plasminogen receptor Plg-RKT was highly expressed by SAMs, suggesting the role of Plg-RKT and plasminogen (PLG) in SAM transformation. In vitro, PLG-treated BMMs transformed into SAMs and expressed SAM functional genes. Knockdown of Plg-RKT blocked the effects of PLG. In vivo, selective knockdown of Plg-RKT in intrahepatic macrophages of BDL- and CCl4-treated mice reduced the number of SAMs and alleviated BDL- and CCl4-induced liver fibrosis, suggesting that Plg-RKT-PLG played an important role in liver fibrosis by mediating SAM transformation. Our findings reveal that SAMs are crucial participants in liver fibrosis. Inhibition of SAM transformation by blocking Plg-RKT might be a potential therapeutic target for liver fibrosis.

Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel.

Background: Lung cancer, most of which is non-small cell lung cancer (NSCLC), is the most common tumor in the world, and drug resistance, as a major problem in clinical treatment, has attracted extensive attention. However, the role and mechanism of Targeting protein for Xenopus kinesin-like protein 2 (TPX2), which is highly expressed in NSCLC, is still unclear. Methods: Bioinformatics analysis was used to analyze the relationship between TPX2 and the clinicopathological features of NSCLC. Stable TPX2 overexpression cell lines with were constructed by lentivirus infection, and the effect of TPX2 on proliferation, migration, invasion and chemoresistance to docetaxel was characterized by the CCK8, wound healing, transwell, colony formation assay and FACS. An in vivo lung homing mouse model was used to further confirmed the role of TPX2 on metastasis. Exosomes were extracted by differential centrifugation from the culture supernatant, and their functions were investigated by co-culture with tumor cells. Gene expression was detected via Western blot and real time PCR (RT-qPCR). Results: Overexpression of TPX2 was related to the poor prognosis of NSCLC. Promoted migration, invasion and metastasis, and reduced the sensitivity of NSCLC cells to docetaxel. The abundance of TPX2 can be packaged in vesicles and transported to other cells. In addition, overexpression of TPX2 induced the accumulation of ß-catenin and C-myc. Conclusion: Our findings indicated that intercellular transfer of exosomal TPX2 triggered metastasis and resistance against to docetaxel in lung cancer cells, through activating downstream WNT/ß-catenin signaling pathway.

Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis.

Biliary atresia (BA) is a severe inflammatory and fibrosing neonatal cholangiopathy disease characterized by progressive obstruction of extrahepatic bile ducts, resulting in cholestasis and progressive hepatic failure. Cholestasis may play an important role in the inflammatory and fibrotic pathological processes, but its specific mechanism is still unclear. Necroptosis mediated by Z-DNA-binding protein 1 (ZBP1)/phosphorylated-mixed lineage kinase domain-like pseudokinase (p-MLKL) is a prominent pathogenic factor in inflammatory and fibrotic diseases, but its function in BA remains unclear. Here, we aim to determine the effect of macrophage necroptosis in the BA pathology, and to explore the specific molecular mechanism. We found that necroptosis existed in BA livers, which was occurred in liver macrophages. Furthermore, this process was mediated by ZBP1/p-MLKL, and the upregulated expression of ZBP1 in BA livers was correlated with liver fibrosis and prognosis. Similarly, in the bile duct ligation (BDL) induced mouse cholestatic liver injury model, macrophage necroptosis mediated by ZBP1/p-MLKL was also observed. In vitro, conjugated bile acid-glycodeoxycholate (GDCA) upregulated ZBP1 expression in mouse bone marrow-derived monocyte/macrophages (BMDMs) through sphingosine 1-phosphate receptor 2 (S1PR2), and the induction of ZBP1 was a prerequisite for the enhanced necroptosis. Finally, after selectively knocking down of macrophage S1pr2 in vivo, ZBP1/p-MLKL-mediated necroptosis was decreased, and further collagen deposition was markedly attenuated in BDL mice. Furthermore, macrophage Zbp1 or Mlkl specific knockdown also alleviated BDL-induced liver injury/fibrosis. In conclusion, GDCA/S1PR2/ZBP1/p-MLKL mediated macrophage necroptosis plays vital role in the pathogenesis of BA liver fibrosis, and targeting this process may represent a potential therapeutic strategy for BA.

RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

Orthogonal threading-through-ß-sheet design of lung cancer EGFR extracellular domain-derived peptidic mimotopes binding to anti-EGFR antibody.

Human epidermal growth factor receptor (EGFR) has been established as a therapeutic target of lung cancer and other diverse tumors. The antibody drug Cetuximab has been developed to target the third subdomain III (TSDIII) of EGFR extracellular domain (ECD) by competitively inhibiting epidermal growth factor binding. In this study, we performed systematic investigation on the crystal complex structure of EGFR ECD domain with Cetuximab to create a residue importance profile for the TSDIII subdomain, based on which a number of U-shaped, double-stranded linear peptides were derived and cyclized to orthogonally thread through most hotspot residues and many responsible residues within the TSDIII ß-sheet plane; they represent mimotopes of the key antibody-recognition site of TSDIII subdomain. Computational analyses revealed that these linear peptides cannot spontaneously fold to the desired conformation in free state due to their intrinsic flexibility. Cell-free assays confirmed that the stapling can considerably improve the binding affinity of linear peptides to Cetuximab by up to 18-fold. The cOrt1 [3-18] cyclic peptide was measured to have the highest affinity in all designed linear and cyclic peptides.

Influence of dietary protein on serum phosphorous levels in peritoneal dialysis patients with different initial transport function.

INTRODUCTION: This cross-sectional study investigated the influence of dietary protein intake (DPI) on serum phosphate levels in peritoneal dialysis (PD) patients and determined the DPI cutoff required to prevent hyperphosphatemia. METHODS: A total of 504 PD patients were categorized into fast (4 h dialysate/plasma [D/P] creatinine clearance ≥0.65) or slow (<0.65) peritoneal transporters. Serum phosphorus and peritoneal solute clearance were compared between the groups with different DPI. RESULTS: The fast peritoneal transporters (n = 233) were older, had lower serum albumin and phosphorus levels, and had higher peritoneal phosphorus clearance (all p < 0.001). Among the slow transporters (n = 271), serum phosphorus levels were significantly higher among patients with DPI > 1.0 g/kg/d (p < 0.001). High DPI only increased the hyperphosphatemia risk in slow transporters (not in high transporters). DPI ≥1.026 g increased the hyperphosphatemia risk in those patients (area under the curve: 0.66, p = 0.001). CONCLUSION: High DPI increases the hyperphosphatemia risk in PD patients with slower peritoneal transport function.

NCQDs active sites as effective collectors of charge carriers towards enhanced photocatalytic activity of porous Co3O4.

In this work, different proportions of N-doped carbon quantum dots/porous Co3O4 (NCQDs/p-Co3O4) NCQDs/Co3O4 composite photocatalysts were prepared by a simple self-assembly method. It was demonstrated by a series of characterizations that 50% NCQDs/Co3O4 has a good visible light response and low electrochemical impedance. The photocatalytic degradation of TC was investigated by the 50% NCQDs/p-Co3O4 composite photocatalyst, and the results showed that the degradation effect of TC reached 81.2% within 120 min. The higher photocatalytic activity of 50% NCQDs/p-Co3O4 was analyzed probably because NCQDs can improve the separation efficiency of photogenerated electron-hole pairs and p-Co3O4 can provide a larger specific surface area and thus has more active sites. This study provides a new strategy for improving the photodegradation activity of Co3O4 photocatalysts.