Nuclear-Targeting Lipid PtIV Prodrug Amphiphile Cooperates with siRNA for Enhanced Cancer Immunochemotherapy by Amplifying Pt-DNA Adducts and Reducing Phosphatidylserine Exposure.

Patients treated with Pt-based anticancer drugs (PtII) often experience severe side effects and are susceptible to cancer recurrence due to the limited bioavailability of PtII and tumor-induced immunosuppression. The exposure of phosphatidylserine on the cell's outer surface induced by PtII results in profound immunosuppression through the binding of phosphatidylserine to its receptors on immune cells. Here, we report a novel approach for enhanced cancer chemoimmunotherapy, where a novel nuclear-targeting lipid PtIV prodrug amphiphile was used to deliver a small interfering RNA (siXkr8) to simultaneously amplify Pt-DNA adducts and reduce the level of exposure of phosphatidylserine. This drug delivery vehicle is engineered by integrating the PtIV prodrug with self-assembly performance and siXkr8 into a lipid nanoparticle, which shows tumor accumulation, cancer cell nucleus targeting, and activatable in a reduced microenvironment. It is demonstrated that nuclear-targeting lipid PtIV prodrug increases the DNA cross-linking, resulting in increased Pt-DNA adduct formation. The synergistic effects of the PtIV prodrug and siXkr8 contribute to the improvement of the tumor immune microenvironment. Consequently, the increased Pt-DNA adducts and immunogenicity effectively inhibit primary tumor growth and prevent tumor recurrence. These results underscore the potential of utilizing the nuclear-targeting lipid PtIV prodrug amphiphile to enhance Pt-DNA adduct formation and employing siXkr8 to alleviate immunosuppression during chemotherapy.

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors.

Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN-targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future-oriented discussion, offering critical insights into the field.

Identification of TEFM as a potential therapeutic target for LUAD treatment.

BACKGROUND: Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. METHODS: We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. RESULTS: Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. CONCLUSION: TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy.

Designing an Implementable Clinical Prediction Model for Near-Term Mortality and Long-Term Survival in Patients on Maintenance Hemodialysis.

RATIONALE & OBJECTIVE: The life expectancy of patients treated with maintenance hemodialysis (MHD) is heterogeneous. Knowledge of life-expectancy may focus care decisions on near-term versus long-term goals. The current tools are limited and focus on near-term mortality. Here, we develop and assess potential utility for predicting near-term mortality and long-term survival on MHD. STUDY DESIGN: Predictive modeling study. SETTING & PARTICIPANTS: 42,351 patients contributing 997,381 patient months over 11 years, abstracted from the electronic health record (EHR) system of midsize, nonprofit dialysis providers. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographics, laboratory results, vital signs, and service utilization data available within dialysis EHR. OUTCOME: For each patient month, we ascertained death within the next 6 months (ie, near-term mortality) and survival over more than 5 years during receipt of MHD or after kidney transplantation (ie, long-term survival). ANALYTICAL APPROACH: We used least absolute shrinkage and selection operator logistic regression and gradient-boosting machines to predict each outcome. We compared these to time-to-event models spanning both time horizons. We explored the performance of decision rules at different cut points. RESULTS: All models achieved an area under the receiver operator characteristic curve of≥0.80 and optimal calibration metrics in the test set. The long-term survival models had significantly better performance than the near-term mortality models. The time-to-event models performed similarly to binary models. Applying different cut points spanning from the 1st to 90th percentile of the predictions, a positive predictive value (PPV) of 54% could be achieved for near-term mortality, but with poor sensitivity of 6%. A PPV of 71% could be achieved for long-term survival with a sensitivity of 67%. LIMITATIONS: The retrospective models would need to be prospectively validated before they could be appropriately used as clinical decision aids. CONCLUSIONS: A model built with readily available clinical variables to support easy implementation can predict clinically important life expectancy thresholds and shows promise as a clinical decision support tool for patients on MHD. Predicting long-term survival has better decision rule performance than predicting near-term mortality. PLAIN-LANGUAGE SUMMARY: Clinical prediction models (CPMs) are not widely used for patients undergoing maintenance hemodialysis (MHD). Although a variety of CPMs have been reported in the literature, many of these were not well-designed to be easily implementable. We consider the performance of an implementable CPM for both near-term mortality and long-term survival for patients undergoing MHD. Both near-term and long-term models have similar predictive performance, but the long-term models have greater clinical utility. We further consider how the differential performance of predicting over different time horizons may be used to impact clinical decision making. Although predictive modeling is not regularly used for MHD patients, such tools may help promote individualized care planning and foster shared decision making.

The Sensitization Differences of Pollen Allergen Components in Patients with Asthma and/or Rhinitis in Southern China.

INTRODUCTION: This study aim to analyzed the main pollen allergen components that cause allergic asthma and/or rhinitis and the cross-reactions between the allergen components. METHODS: Twenty one allergic rhinitis patients and 23 allergic asthma patients with pollen sensitization from the China Biological Information Repository of Respiratory Diseases were included. All the patients were detected serum pollen allergens components specific immunoglobulin E (sIgE) including Betula verrucosa (Bet v 1, Bet v 2, Bet v 4), Quercus alba (Pla a 1, Pla a 2), Ambrosia elatior (Amb a 1), Artemisia vulgaris (Art v 1, Art v 3, Art v 4), Bermuda grass (Cyn d 1, Cyn d 12), Phleum pratense (Phl p 5, Phl p 1, Phl p 4, Phl p 7, Phl p 12), and cross-reactive carbohydrate determinants. RESULTS: In patients with asthma, Phl p 4 had the highest positive rate (60.9%), followed by Phl p 1 (43.5%) and Pla a 2 (34.8%), while in patients with rhinitis, Amb a 1 had the highest positive rate (71.4%), followed by Phl p 4 (61.9%) and Pla a 2 (42.9%). Meanwhile, Phl p 1 (43.5%) in asthma patients was higher than that in rhinitis (4.7%, p = 0.03), while Amb a 1 (71.4%) in rhinitis patients was higher than that in asthma (26.1%, p = 0.03). Interestingly, optimal scale analysis show that the severity of both asthma and rhinitis is related to Bet v 4 (Cronbach's Alpha = 95.0%). CONCLUSIONS: In general, Phl p 4 is the main allergenic component in pollen sensitized asthma patients, while Amb a 1 is the main allergenic component in pollen sensitized rhinitis patients. Sensitization to Bet v 4 may lead to more severe symptoms, and this result may be applied in future clinical precise diagnosis.

Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform.

Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.

Revolutionizing lymph node metastasis imaging: the role of drug delivery systems and future perspectives.

The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development.

Surface profile measurement and parameter analysis of silicon wafers in the upright state.

A novel approach, to the best of our knowledge, is presented for assessing silicon wafer surface profiles using an interferometer and vertically rotatable wafer holder. This approach significantly enhances precision and reduces costs, and outperforms traditional techniques in measurement consistency and accuracy. It effectively reduces sample distortion and positional shifts owing to the removal and reinstallation of the wafers. Using this method, a global backsurface-referenced ideal range of 0.385 µm, warp of 0.193 µm, and other parameters were obtained, demonstrating its practicality in efficiently capturing key surface profile metrics for silicon wafers. This innovation promises substantial improvements in high-volume wafer surface profile testing, overcoming prevalent technological challenges in this industry.

Exploring approaches to pulp vitality assessment: A scoping review of nontraditional methods.

INTRODUCTION: Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. METHODS: The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: "What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well-known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. RESULTS: Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope-labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. CONCLUSIONS: This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios.

Research on mining land subsidence by intelligent hybrid model based on gradient boosting with categorical features support algorithm.

Land subsidence induced by coal mining (MLS) has posed a huge threat to the ecological environment, buildings, roads, and other infrastructure safety in mining areas. However, the prediction and evaluation of MLS is relatively complex, and the reliability of the prediction results is closely related to factors such as the professional knowledge and engineering experience of researchers. This paper aims to combine intelligent optimization algorithms: ant lion optimizer (ALO), bald eagle search (BES), bird swarm algorithm (BSA), harris hawks optimization (HHO), and sparrow search algorithm (SSA), with machine learning model of gradient boosting with categorical features support algorithm (CatBoost) to predict MLS. To achieve this goal, five hybrid models based CatBoost were developed and the prediction accuracy and reliability of the models were compared and analyzed. The prediction performance of the hybrid models has been significantly improved on the basis of a single model, of which the SSA-CatBoost model has the most obvious improvement (from R2 = 0.927 to 0.965, RMSE = 0.541 to 0.377, MAE = 0.386 to 0.297, VAF = 92.720 to 95.837). The importance and predictive contribution of all input features to predictive labels were studied with the Shapley method. The research results indicate that hybrid model technology is a reliable MLS prediction method. This study can help mining technicians use machine learning methods to study the degree of MLS damage to the surface environment and provide scientific advanced prediction and evaluation for the protection and management of the ecological environment in mining areas and the formulation of safety production measures.

Deep learning in the diagnosis of maxillary sinus diseases: A systematic review.

OBJECTIVES: To assess the performance of deep learning (DL) in the detection, classification, and segmentation of maxillary sinus diseases. MATERIALS AND METHODS: An electronic search was conducted by two reviewers on databases including PubMed, Scopus, Cochrane, and IEEE. All English papers published no later than February 7, 2024, were evaluated. Studies related to DL for diagnosing maxillary sinus diseases were also searched in journals manually. RESULTS: 14 of 1167 studies were eligible according to the inclusion criteria. All studies trained DL models based on radiographic images. Six studies applied to detection tasks, one focused on classification, two segmented lesions, and five studies made a combination of 2 types of DL models. The accuracy of the DL algorithms ranged from 75.7% to 99.7%, and the area under curves (AUC) varied between 0.7 and 0.997. CONCLUSION: DL can accurately deal with the tasks of diagnosing maxillary sinus diseases. Students, residents, and dentists could be assisted by DL algorithms to diagnose and make rational decisions on implant treatment related to maxillary sinuses.

The application of lasers in vital pulp therapy: clinical and radiographic outcomes.

The main purpose of vital pulp therapy (VPT) is to preserve the integrity and function of the pulp. A wide variety of materials and techniques have been proposed to improve treatment outcomes, and among them, the utilization of lasers has gained significant attention. The application of lasers in different stages of VPT has witnessed remarkable growth in recent years, surpassing previous approaches.This study aimed to review the applications of lasers in different steps of VPT and evaluate associated clinical and radiographic outcomes. An electronic search using Scopus, MEDLINE, Web of Science and Google Scholar databases from 2000 to 2023 was carried out by two independent researchers. The focus was on human studies that examined the clinical and/or radiographic effects of different laser types in VPT. A total of 4243 studies were included in this narrative review article. Based on the compiled data, it can be concluded that although current literature suggests laser may be proposed as an adjunct modality for some procedural steps in VPT, more research with standardized methodologies and criteria is needed to obtain more reliable and conclusive results.

[Research Progress in the Association Between Sarcopenic Obesity and Cancer].

As the global prevalence of obesity and the elderly population continues to increase,the incidence of sarcopenic obesity is also on the rise and becoming a global public health concern.Sarcopenic obesity not only increases the incidence of cancer,but is also associated with poor clinical outcomes in various cancers,such as surgical complications,increased risk of death,and possibly even an impact on chemotherapy as well.Therefore,sarcopenic obesity is emerging as an important indicator of prognosis in cancer patients.However,there are limited relevant studies on the association between sarcopenic obesity and cancer in China.This article reviews the definition and diagnosis of sarcopenic obesity,the clinical correlation between sarcopenic obesity and cancer,and the potential mechanisms,with a view to providing a reference for future clinical practice in China.

Racial differences in the effect of APOE-ε4 genotypes on trail making test B in Alzheimer's disease: A longitudinal study.

OBJECTIVES: The trail making test part B (TMT-B) evaluates executive functions, memory, and sensorimotor functions. No previous study was found to examine the longitudinal effect of APOE-ε4 genotypes on the TMT-B scores in Alzheimer's disease (AD) across racial groups. METHODS: This study used the data from Alzheimer's Disease Neuroimaging Initiative (ADNI): 382 participants with AD, 503 with cognitive normal (CN), 1293 with mild cognitive impairment (MCI) at baseline and follow-up of four years. The multivariable linear mixed model was used to investigate the effect of APOE-ε4 genotypes on changes in TMT-B scores. RESULTS: Compared with Whites, African Americans (AA) and Hispanics had higher TMT-B scores (poor cognitive function). Furthermore, Whites subjects with 1 or 2 APOE-ε4 alleles had significantly higher TMT-B scores compared with individuals without APOE-ε4 allele at baseline and four follow-up visits; however, no differences in TMT-B were found between APOE-ε4 alleles in the Hispanic and AA groups. No APOE-ε4 by visit interactions was found for 3 racial groups. Stratified by AD diagnosis, the APOE-ε4 allele was associated with TMT-B scores only in the MCI group, while there were significant interactions for visit by education, APOE-ε4 allele, and the Mini Mental State Examination (MMSE) score in the MCI group. In addition, TMT-B was significantly correlated with the MMSE, AD Assessment Scale-cognitive subscale 13 (ADAS13), tTau, pTau, Aß42, and hippocampus. CONCLUSIONS: APOE-ɛ4 allele is associated with TMT-B scores in Whites subjects, but not in the Hispanic and AA groups. APOE-ε4 showed interaction with visit in the MCI group.

A case of anaphylactic shock to human fibrinogen infusion during cardiac surgery.

Human fibrinogen (FIB) has been clinically proven to be considerably effective for the treatment of postoperative bleeding, with reported cases of allergic reactions to human FIB being rare. Here, we report a case of an anaphylactic shock in 27-year-old patients with rheumatic heart valve disease who received a human FIB infusion during mitral valve replacement, aortic valve replacement, and tricuspid valve-shaping surgery. The patients showed generalised profuse sweating, a barely noticeable skin rash, faint pulse, systolic pressure < 50 mmHg, and a heart rate of 71 beats/min. We share insights from a case of severe allergy to human FIB infusion during cardiac surgery, through which we have gained experience in the processes of diagnosing and treating. This report aims to provide a preliminary summary of the characteristics of this case to serve as a reference for fellow clinicians.

Application of artificial intelligence in dental implant prognosis: A scoping review.

OBJECTIVES: The purpose of this scoping review was to evaluate the performance of artificial intelligence (AI) in the prognosis of dental implants. DATA: Studies that analyzed the performance of AI models in the prediction of implant prognosis based on medical records or radiographic images. Quality assessment was conducted using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi-Experimental Studies. SOURCES: This scoping review included studies published in English up to October 2023 in MEDLINE/PubMed, Embase, Cochrane Library, and Scopus. A manual search was also performed. STUDY SELECTION: Of 892 studies, full-text analysis was conducted in 36 studies. Twelve studies met the inclusion criteria. Eight used deep learning models, 3 applied traditional machine learning algorithms, and 1 study combined both types. The performance was quantified using accuracy, sensitivity, specificity, precision, F1 score, and receiver operating characteristic area under curves (ROC AUC). The prognostic accuracy was analyzed and ranged from 70 % to 96.13 %. CONCLUSIONS: AI is a promising tool in evaluating implant prognosis, but further enhancements are required. Additional radiographic and clinical data are needed to improve AI performance in implant prognosis. CLINICAL SIGNIFICANCE: AI can predict the prognosis of dental implants based on radiographic images or medical records. As a result, clinicians can receive predicted implant prognosis with the assistance of AI before implant placement and make informed decisions.

Fabrication of magnetic Fe3O4 doped ß-cyclodextrin microporous organic network for the efficient extraction of endocrine disrupting chemicals from food takeaway boxes.

Endocrine disrupting chemicals (EDCs) are a typical class of natural or man-made endogenous hormone agonists or antagonists that can directly or potentially interfere with human endocrine system. However, it is still difficult to analyze trace EDCs directly from complex environment and food matrices. Therefore, the proper sample pretreatment is highly desired and the preparation of efficient adsorbents is of great challenge and importance. Herein, we report the facile one-pot solvothermal synthesis of Fe3O4 nanoparticle doped magnetic ß-cyclodextrin microporous organic network composites (MCD-MONs) for the magnetic solid phase extraction (MSPE) of four phenolic EDCs in water and food takeaway boxes prior to the high-performance liquid chromatography analysis. The sheet-like Fe3O4 doped MCD-MONs offered good magnetic property (16.5 emu g-1) and stability, and provided numerous hydrogen bonding, hydrophobic, π-π, and host-guest interaction sites for EDCs. Under the optimal experimental conditions, the established method was successfully verified with wide linear range (2.0-1000 µg L-1), low limits of detection (0.6-1.0 µg L-1), good precisions (intra-day and inter-day RSDs < 5.2 %, n = 3), large enrichment factors (88-98) and adsorption capacity (90.3-255.8 mg g-1), short extraction time (6 min), less adsorbent consumption (3 mg), and good reusability (at least 8 times) for EDCs. The proposed method was successfully applied to detect the trace EDCs in real samples with the recovery of 84.0-99.7 %. This work demonstrated the great potential of MCD-MONs for the efficient MSPE of trace EDCs from complex food takeaway boxes and water samples and uncovered the prospect of CD-based MONs in sample pretreatment.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis.

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). AIM: To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC. METHODS: Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. RESULTS: GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). CONCLUSION: This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Thiol-yne click post-synthesis of phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network for selective and efficient extraction of antiepileptic drugs.

Owing to their incomplete digestion in the human body and inadequate removal by sewage treatment plants, antiepileptic drugs (AEDs) accumulate in water bodies, potentially affecting the exposed humans and aquatic organisms. Therefore, sensitive and reliable detection methods must be urgently developed for monitoring trace AEDs in environmental water samples. Herein, a novel phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON-PBA) was designed and synthesized via the thiol-yne click post-modification strategy for selective and efficient magnetic solid-phase extraction (MSPE) of trace AEDs from complex sample matrices through the specific B-N coordination, π-π, hydrogen bonding, electrostatic, and host-guest interactions. Fe3O4@CD-MON-PBA exhibited a large surface area (118.5 m2 g-1), rapid magnetic responsiveness (38.6 emu g-1, 15 s), good stability and reusability (at least 8 times), and abundant binding sites for AEDs. Under optimal extraction conditions, the proposed Fe3O4@CD-MON-PBA-MSPE-HPLC-UV method exhibited a wide linear range (0.5-1000 µg L-1), low limits of detection (0.1-0.5 µg L-1) and quantitation (0.3-2 µg L-1), good anti-interference ability, and large enrichment factors (92.2-104.3 to 92.3-98.0) for four typical AEDs. This work confirmed the feasibility of the thiol-yne click post-synthesis strategy for constructing novel and efficient multifunctional magnetic CD-MONs for sample pretreatment and elucidated the significance of B-N coordination between PBA and N-containing AEDs.

Complete mitochondrial genome of Devario shanensis (Cypriniformes: Danionidae: Danioninae): genome characterization and phylogenetic consideration.

In this study, a comprehensive analysis is presented on the complete mitochondrial genome and phylogenetic relationships of Devario shanensis, an endemic species to the Irrawaddy drainage in southwestern China. The complete mitogenome sequence of D. shanensis was sequenced to be 16,860 bp long and encompassed 13 protein-coding genes, 22 tRNA genes, two rRNA genes and a non-coding control region. The overall AT content (61.1%) was much higher than GC content (38.9%). Phylogenetic analyses employing maximum-likelihood and Bayesian inference methods on the complete mitogenomes, including D. shanensis and 13 other species, unveiled a close genomic relationship between D. shanensis and Devario interruptus. This work will contribute to the genetic resource enrichment and phylogenetic researches on genus Devario.