Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment.

BACKGROUND: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. METHODS: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4-CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. RESULTS: The percentages of patients in none CTC, OCT4-CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4-CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4-CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. CONCLUSION: OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.

Global analysis of the adverse effects of micro- and nanoplastics on intestinal health and microbiota of fish.

The wide occurrence of micro- and nanoplastics (MPs/NPs) within aquatic ecosystems has raised increasing concerns regarding their potential effects on aquatic organisms. However, the effects of MPs/NPs on intestinal health and microbiota of fish remain controversial, and there is a lack of comprehensive understanding regarding how the impact of MPs/NPs is influenced by MPs/NPs characteristics and experimental designs. Here, we conducted a global analysis to synthesize the effects of MPs/NPs on 47 variables associated with fish intestinal health and microbiota from 118 studies. We found that MPs/NPs generally exerted obvious adverse effects on intestinal histological structure, permeability, digestive function, immune and oxidative-antioxidative systems. By contrast, MPs/NPs showed slight effects on intestinal microbial variables. Further, we observed that the responses of intestinal variables to MPs/NPs were significantly regulated by MPs/NPs characteristics and experimental designs. For instance, polyvinyl chloride plastics showed higher toxicity to fish gut than polyethylene and polystyrene did. Additionally, larval fish appeared to be more sensitive to MPs/NPs than juvenile fish. Collectively, this study highlights the potential impacts of MPs/NPs on intestinal health and microbiota of fish, and underscores the determinant role of MPs/NPs characteristics and experimental designs in MPs/NPs toxicity.

Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Low-carbon energy transition multi-agent network evolutionary under carbon trading scheme.

Transitioning to low-carbon energy is key for reaching carbon neutrality and modernizing our energy systems, but it presents significant cost-related challenges for energy businesses. To foster optimal outcomes, this paper develops a game model including power generators, high-energy businesses, and consumers in the carbon trading framework. The model explores how different entities evolve their low-carbon strategies under social learning influence to optimize utility. Stability analysis of strategy and simulation experiments reveal the following findings: (1) Greater carbon quotas reduce power generators' low-carbon transition willingness while high-energy-consuming enterprises and consumers remain unchanged. (2) Higher prices for low-carbon products offered by high-energy-consuming enterprises boost low-carbon transition motivation across all parties. (3) Increased green premiums enhance revenue for all parties but are constrained by policy and carbon pricing. (4) Both direct and indirect increases in carbon emissions negatively impact the revenue and utility for all stakeholders. (5) Increasing social learning effect fosters a shift towards low-carbon strategies, accelerating the attainment of game equilibrium, and enhancing market stability and sustainability. This research provides decision support for carbon trading policy design and low-carbon transition of energy enterprises.

The role of the CXCR6/CXCL16 axis in the pathogenesis of fibrotic disease.

CXC chemokine receptor 6 (CXCR6), a seven-transmembrane domain G-protein-coupled receptor, plays a pivotal regulatory role in inflammation and tissue damage through its interaction with CXC chemokine ligand 16 (CXCL16). This axis is implicated in the pathogenesis of various fibrotic diseases and correlates with clinical parameters that indicate disease severity, activity, and prognosis in organ fibrosis, including afflictions of the liver, kidney, lung, cardiovascular system, skin, and intestines. Soluble CXCL16 (sCXCL16) serves as a chemokine, facilitating the migration and recruitment of CXCR6-expressing cells, while membrane-bound CXCL16 (mCXCL16) functions as a transmembrane protein with adhesion properties, facilitating intercellular interactions by binding to CXCR6. The CXCR6/CXCL16 axis is established to regulate the cycle of damage and repair during chronic inflammation, either through modulating immune cell-mediated intercellular communication or by independently influencing fibroblast homing, proliferation, and activation, with each pathway potentially culminating in the onset and progression of fibrotic diseases. However, clinically exploiting the targeting of the CXCR6/CXCL16 axis requires further elucidation of the intricate chemokine interactions within fibrosis pathogenesis. This review explores the biology of CXCR6/CXCL16, its multifaceted effects contributing to fibrosis in various organs, and the prospective clinical implications of these insights.

Combined effect of freshwater salinization and harmful algae on the benthic invertebrate Chironomus pallidivittatus.

Global climate change as well as human activities have been reported to increase the frequency and severity of both salinization and harmful algal blooms (HABs) in many freshwater systems, but their co-effect on benthic invertebrates has rarely been studied. This study simultaneously examined the joint toxicity of salinity and different cyanobacterial diets on the behavior, development, select biomarkers, and partial life cycle of Chironomus pallidivittatus (Diptera). High concentrations of salts (e.g., 1 g/L Ca2+ and Mg2+) and toxic Microcystis had synergistic toxicity, inhibiting development, burrowing ability and causing high mortality of C. pallidivittatus, especially for the Mg2+ treatment, which caused around 90% death. Low Ca2+ concentration (e.g., 0.01 g/L) promoted larval burrowing ability and inhibited toxin accumulation, which increased the tolerance of Chironomus to toxic Microcystis. However, low Mg2+ concentration (e.g., 0.01 g/L) was shown to inhibit the behavior, development and increase algal toxicity to Chironomus. Toxic Microcystis resulted in microcystin (MC) accumulation, inhibited the burrowing ability of larvae, and increased the proportion of male adults (>50%). The combined toxicity level from low to high was verified by the weight of evidence and the grey TOPSIS model, which integrated five lines of evidence to increase the risk assessment accuracy and efficiency. This is the first study that provided insights into ecological risk arising from the joint effect of salinity and harmful algae on benthic organisms. We suggest that freshwater salinization and HABs should be considered together when assessing ecological threats that arise from external stress.

Enhancing coevolutionary signals in protein-protein interaction prediction through clade-wise alignment integration.

Protein-protein interactions (PPIs) play essential roles in most biological processes. The binding interfaces between interacting proteins impose evolutionary constraints that have successfully been employed to predict PPIs from multiple sequence alignments (MSAs). To construct MSAs, critical choices have to be made: how to ensure the reliable identification of orthologs, and how to optimally balance the need for large alignments versus sufficient alignment quality. Here, we propose a divide-and-conquer strategy for MSA generation: instead of building a single, large alignment for each protein, multiple distinct alignments are constructed under distinct clades in the tree of life. Coevolutionary signals are searched separately within these clades, and are only subsequently integrated using machine learning techniques. We find that this strategy markedly improves overall prediction performance, concomitant with better alignment quality. Using the popular DCA algorithm to systematically search pairs of such alignments, a genome-wide all-against-all interaction scan in a bacterial genome is demonstrated. Given the recent successes of AlphaFold in predicting direct PPIs at atomic detail, a discover-and-refine approach is proposed: our method could provide a fast and accurate strategy for pre-screening the entire genome, submitting to AlphaFold only promising interaction candidates-thus reducing false positives as well as computation time.

Toxic effects and comparison of common amino antioxidants (AAOs) in the environment on zebrafish: A comprehensive analysis based on cells, embryos, and adult fish.

The ubiquity of amino antioxidants (AAOs) in the environment has attracted increasing attention, given their potential toxicity. This investigation represents a pioneering effort, systematically scrutinizing the toxicological effects of four distinct AAOs across the developmental spectrum of zebrafish, encompassing embryonic, larvae, and adult stages. The results indicate that four types of AAO exhibit varying degrees of cell proliferation toxicity. Although environmentally relevant concentrations of AAOs exhibit a comparatively circumscribed impact on zebrafish embryo development, heightened concentrations (300 µg/L) of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD) distinctly evoke developmental toxicity. Behavioral analysis results indicate that at concentrations of 20 and 300 µg/L, the majority of AAOs significantly reduced the swimming speed and activity of larvae. Moreover, each AAO triggers the generation of reactive oxygen species (ROS) in larvae, instigating diverse levels of oxidative stress. The study delineates parallel toxicological patterns in zebrafish exposed to 300 µg/L of 6PPD and IPPD, thereby establishing a comparable toxicity profile. The comprehensive toxicity effects among the four AAOs is as follows: IPPD >6PPD > N-Phenyl-1-naphthylamine (PANA) > diphenylamine (DPA). These findings not only enrich our comprehension of the potential hazards associated with AAOs but also provide data support for structure-based toxicity prediction models.

Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

Design, Synthesis, and Biological Evaluation of Pierardine Derivatives as Novel Brain-Penetrant and In Vivo Potent NMDAR-GluN2B Antagonists for Ischemic Stroke Treatment.

A series of structurally novel GluN2B NMDAR antagonists were designed, synthesized, and biologically evaluated as anti-stroke therapeutics by optimizing the chemical structure of Pierardine, the active ingredient of traditional Chinese medicine Dendrobium aphyllum (Roxb.) C. E. Fischer identified via in silico screening. The systematic structure-activity relationship study led to the discovery of 58 with promising NMDAR-GluN2B binding affinity and antagonistic activity. Of the two enantiomers, S-58 exhibited significant inhibition (IC50 = 74.01 ± 12.03 nM) against a GluN1/GluN2B receptor-mediated current in a patch clamp assay. In addition, it displayed favorable specificity over other subtypes and off-target receptors. In vivo, S-58 exerted therapeutic efficacy comparable to that of the approved GluN2B NMDAR antagonist ifenprodil and excellent safety profiles. In addition to the attractive in vitro and in vivo potency, S-58 exhibited excellent brain exposure. In light of these merits, S-58 has been advanced to further preclinical investigation as a potential anti-stroke candidate.

Beneficial Effects of Low-Dose Intravenous Dexmedetomidine Premedication in Patient Undergoing Laparoscopic Cholecystectomy Under General Anesthesia: A Prospective, Double-Blind, Randomized Controlled Trial.

Purpose: Dexmedetomidine (Dex) is a potent and highly selective α2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC). Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 µg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded. Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P>0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P<0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P<0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P<0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P<0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P<0.05 for all). Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 µg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.

Interfacial Electron Engineering of PdSn-NbN/C for Highly Efficient Cleavage of the C-C Bonds in Alkaline Ethanol Electrooxidation.

The splitting of the C-C bonds of ethanol remains a key issue to be addressed, despite tremendous efforts made over the past several decades. This study highlights the enhancement mechanism of inexpensive NbN-modified Pd1 Sn3 -NbN/C towards the C-C bonds cleavage for alkaline ethanol oxidation reaction (EOR). The optimal Pd1 Sn3 -NbN/C delivers a catalytic activity up to 43.5 times higher than that of commercial Pd/C and high carbonate selectivity (20.5%) toward alkaline EOR. Most impressively, the Pd1 Sn3 -NbN/C presents good durability even after 25 200 s of chronoamperometric testing. The enhanced catalytic performance is mainly due to the interfacial interaction between PdSn and NbN, demonstrated by multiple structural characterization results. In addition, in situ ATR-SEIRAS (Attenuated total reflection-surface enhanced infrared absorption spectroscopy) results suggest that NbN facilitates the C-C bonds cleavage towards the alkaline EOR, followed by the enhanced OH adsorption to promote the subsequent oxidation of C1 intermediates after doping Sn. DFT (density functional theory) calculations indicate that the activation barriers of the C-H bond cleavage in CH3 CH2 OH, CH3 CHOH, CH3 CHO, CH3 CO, CH2 CO, and the C-C bond cleavage in CH3 CO, CH2 CO, CHCO are evidently reduced and the removal of adsorbed CH3 CO and CO becomes easier on the PdSn-NbN/C catalyst surface.

ACT001 alleviates inflammation and pyroptosis through the PPAR-γ/NF-κB signaling pathway in LPS-induced alveolar macrophages.

BACKGROUND: ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. OBJECTIVE: The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. METHODS: NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. RESULTS: Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. CONCLUSION: ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages.

A Radiomics Model Based on CT Images Combined with Multiple Machine Learning Models to Predict the Prognosis of Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: We aimed to construct 3 predictive models, including a clinical model, a radiomics model, and a combined model, to forecast the discharge prognosis of patients with intracerebral hemorrhage on admission. METHODS: A retrospective study was conducted, involving a total of 161 patients with intracerebral hemorrhage (ICH). At a ratio of 7:3, 115 of these patients were assigned to the training cohort, and 46 of these patients were assigned to the validation cohort. To produce the radionics signature and pick the features to use in its construction, the least absolute shrinkage and selection operator (LASSO) regression was applied. Five machine models were applied, and the optimal model was chosen to construct the radionics model. A clinical model was constructed using univariate and stepwise analysis to identify independent risk variables for poor outcomes at discharge. A predictive combined model nomogram was generated by integrating the clinical model and radiomics model. The performance of the nomogram was assessed in the training cohort and validated in the validation cohort. Analyses of the receiver operating characteristic curve (ROC), the calibration curve, and the decision curve were performed to assess the performance of the combined model. RESULTS: This study encompassed a cohort of 161 individuals diagnosed with intracerebral hemorrhage (ICH), consisting of 110 males and 51 females. Utilizing the modified Rankin Scale (mRS) at discharge, the analysis revealed that 89 patients (55.3%) had a good prognosis, while 72 patients (44.7%) had a poor prognosis. Only 8 out of 1130 radiomics features were selected and used in conjunction with the LR algorithm to develop the radiomics model. Sex, IVH, GCS score, and ICH volume were determined to be independent predictors of poor outcomes at the time of discharge. The AUC values of the combined model, radiomics model, and clinical model were 0.8583, 0.8364, and 0.7579 in the training cohort, and 0.9153, 0.8692, and 0.7114 in the validation cohort, respectively. The combined model nomogram exhibited good calibration and clinical benefit in both the training and validation cohorts. The decision curve analysis (DCA) displays that the combined model obtained the highest net benefit compared to the radiomics model and clinics model in the training cohort. CONCLUSIONS: The combined model demonstrates reliability and efficacy in predicting the discharge prognosis of ICH, enabling physicians to perform individualized risk assessments, and make optimal choices about patients with ICH.

Quantitative Analysis of Photochemical Reactions in Pentacene Precursor Films.

On-surface reactions are rapidly gaining attention as a chemical technique for synthesizing organic functional materials, such as graphene nanoribbons and molecular semiconductors. Quantitative analysis of such reactions is essential for fabricating high-quality film structures, but until our recent work using p-polarized multiple-angle incidence resolution spectrometry (pMAIRS), no analytical technique is available to quantify the reaction rate. In the present study, the pMAIRS technique is employed to analyze the photochemical reaction from 6,13-dihydro-6,13-ethanopentacene-15,16-dione to pentacene in thin films. The spectral analysis on a pMAIRS principle readily reveals the photoconversion rate accurately without other complicated calculations. Thus, this study underlines that the pMAIRS technique is a powerful tool for quantitative analysis of on-surface reactions, as well as molecular orientation.

New insights on mitochondrial heteroplasmy observed in ovarian diseases.

BACKGROUND: The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence of histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers to the coexistence of wild-type and mutant mtDNA. Most healthy individuals carry a low point mutation load (<1 %) in their mtDNA, typically without any discernible phenotypic effects. However, as it exceeds a certain threshold, it may cause the onset of various diseases. Since the ovary is a highly energy-intensive organ, it relies heavily on mitochondrial function. Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders. AIM OF REVIEW: In this review, we have elucidated the close relationship between mtDNA heteroplasmy and ovarian diseases, and summarized novel avenues and strategies for the potential treatment of these ovarian diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW: Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders, including polycystic ovary syndrome, premature ovarian insufficiency, and endometriosis. Current strategies related to mitochondrial heteroplasmy are untargeted and have low bioavailability. Nanoparticle delivery systems loaded with mitochondrial modulators, mitochondrial replacement/transplantation therapy, and mitochondria-targeted gene editing therapy may offer promising paths towards potentially more effective treatments for these diseases, despite ongoing challenges.

DARS2 promotes the occurrence of lung adenocarcinoma via the ERK/c-Myc signaling pathway.

BACKGROUND: DARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored. METHODS: In this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan-Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway. RESULTS: DARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c-Myc signaling pathway. CONCLUSION: Our data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.

Research on an Enhanced Detuned-Loading Effect in Integrated Two-Section DFB Lasers with High Modulation Bandwidths.

A novel high-speed directly modulated two-section distributed-feedback (TS-DFB) semiconductor laser based on the detuned-loading effect is proposed and simulated. A grating structure is designed by the reconstruction-equivalent-chirp (REC) technique. A π phase shift is introduced into the reflection grating, which can provide a narrow-band reflection region with a sharp falling slope on both sides of the reflection spectrum, thus enhancing the detuned-loading effect. Owing to its unique dual-falling-edges structure, the bandwidth can be improved even when the lasing wavelength shifts beyond the left falling edge due to a thermal effect in the actual test, in which condition the detuned-loading effect can be used twice, which greatly improves the yield. The modulation bandwidth is increased from 17.5 GHz for a single DFB laser to around 24 GHz when the lasing wavelength is located on the left falling edge of the TS-DFB laser based on the detuned-loading effect, and it can be increased to 22 GHz for the right side. An eight-channel laser array with precise wavelength spacing is investigated, with a side-mode suppression ratio (SMSR) >36 dB. In addition, TS-DFB lasers with uniform reflection gratings are studied, and simulated results show that the modulation characteristic is far inferior to the laser with a phase-shifted grating reflector.

Magnetic induction heating and drug release properties of magnetic carbon nanotubes.

AIM: The use of magnetic carbon nanotubes for multi-modal cancer treatment, incorporating both hyperthermia and drug delivery functions, has drawn substantial interest. Yet, the present method of regulating hyperthermia temperature involves manually adjusting the magnetic field intensity, adding to the complexity and difficulty of clinical applications. This study seeks to design novel magnetic carbon nanotubes capable of self-temperature regulation, and investigate their drug loading and release characteristics. METHODS: Using the co-precipitation method, we synthesized magnetic carbon nanotubes with a Curie temperature of 43 °C. A comprehensive investigation was conducted to analyze their morphology, crystal structure, and magnetic characteristics. To enhance their functionality, chitosan and sodium alginate modifications were introduced, enabling the loading of the antitumor drug doxorubicin hydrochloride (DOX) into these magnetic carbon nanotubes. Subsequently, the loading and release properties of DOX were investigated within the modified magnetic nanotubes. RESULTS: Under alternating magnetic field, magnetic carbon nanotubes exhibit self-regulating properties by undergoing a magnetic phase transition, maintaining temperatures around 43 °C as required for hyperthermia. On the other hand, during magnetic induction heating, the release percentage of DOX reached 23.5% within 2 h and 71.7% within 70 h at tumor pH conditions, indicating their potential for sustained drug release. CONCLUSIONS: The prepared magnetic carbon nanotubes can effectively regulate the temperature during hyperthermia treatment while ensuring controlled drug release, which presents a promising method for preparing nanomaterials that synergistically enhance magnetic hyperthermia and chemotherapy drugs.