Efficacy and safety of fospropofol disodium sedation for same-day bidirectional endoscopy in elderly patients: protocol for a prospective, single-center, randomized, double-blind, non-inferiority trial.

Introduction: Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties when compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients. Methods and analysis: This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 patients aged 65 years or older, who are scheduled for same-day bidirectional endoscopy under sedation, will be randomly allocated, in a 1:1 ratio, to either fospropofol group or propofol group (n = 128 in each group). All patients will receive analgesic pre-treatment with sufentanil 5 µg. Two minutes later, an initial bolus dose of fospropofol 6.5 mg/kg or 1.5 mg/kg propofol and supplemental doses of fospropofol 1.6 mg/kg or 0.5 mg/kg propofol will be titrated as needed to achieve target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events concerning cough reflex, gag reflexes, body movement, muscular tremor, and pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), and bradycardia, will also be recorded. Data will be analyzed on an intention-to-treat basis. Discussion: We hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. Our findings will potentially provide a new sedation regimen for same-visit bidirectional endoscopy in elderly patients. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02875639.

Natural compounds from herbs and nutraceuticals as glycogen synthase kinase-3ß inhibitors in Alzheimer's disease treatment.

BACKGROUND: Alzheimer's disease (AD) pathogenesis is complex. The pathophysiology is not fully understood, and safe and effective treatments are needed. Glycogen synthase kinase 3ß (GSK-3ß) mediates AD progression through several signaling pathways. Recently, several studies have found that various natural compounds from herbs and nutraceuticals can significantly improve AD symptoms. AIMS: This review aims to provide a comprehensive summary of the potential neuroprotective impacts of natural compounds as inhibitors of GSK-3ß in the treatment of AD. MATERIALS AND METHODS: We conducted a systematic literature search on PubMed, ScienceDirect, Web of Science, and Google Scholar, focusing on in vitro and in vivo studies that investigated natural compounds as inhibitors of GSK-3ß in the treatment of AD. RESULTS: The mechanism may be related to GSK-3ß activation inhibition to regulate amyloid beta production, tau protein hyperphosphorylation, cell apoptosis, and cellular inflammation. By reviewing recent studies on GSK-3ß inhibition in phytochemicals and AD intervention, flavonoids including oxyphylla A, quercetin, morin, icariin, linarin, genipin, and isoorientin were reported as potent GSK-3ß inhibitors for AD treatment. Polyphenols such as schisandrin B, magnolol, and dieckol have inhibitory effects on GSK-3ß in AD models, including in vivo models. Sulforaphene, ginsenoside Rd, gypenoside XVII, falcarindiol, epibrassinolides, 1,8-Cineole, and andrographolide are promising GSK-3ß inhibitors. CONCLUSIONS: Natural compounds from herbs and nutraceuticals are potential candidates for AD treatment. They may qualify as derivatives for development as promising compounds that provide enhanced pharmacological characteristics.

Driving Efficiency: Leveraging Model-Informed Approaches in 505(b)(2) Regulatory Actions.

Introduced by the Hatch-Waxman Amendments of 1984, 505(b)(2) applications permit the US Food and Drug Administration to rely, for approval of a new drug application, on information from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. This pathway is designed to circumvent the unnecessary duplication of studies already conducted on a previously approved drug. It can lead to a considerably more efficient and expedited route to approval compared to a traditional development path. Model-informed drug development refers to the utilization of a diverse array of quantitative models in drug development to streamline the decision-making process. In this approach, diverse quantitative models that integrate knowledge of physiology, disease processes, and drug pharmacology are employed to address drug development challenges and guide regulatory decisions. Integration of these model-informed approaches into 505(b)(2) regulatory submissions and decision-making can further expedite the approval of new drugs. This article discusses some applications of model-informed approaches that were used to support 505(b)(2) drug development and regulatory actions. Specifically, various quantitative models such as population pharmacokinetic and exposure-response models have been employed to provide evidence of effectiveness, guide dosing in subgroups such as subjects with hepatic or renal impairment, and inform policies. These case study examples collectively underscore the significance of model-informed approaches in drug development and regulatory decisions associated with 505(b)(2) submissions.

Geminivirus C4/AC4 proteins hijack cellular COAT PROTEIN COMPLEX I for chloroplast targeting and viral infections.

Geminiviruses infect numerous crops and cause extensive agricultural losses worldwide. During viral infection, geminiviral C4/AC4 proteins relocate from the plasma membrane to chloroplasts, where they inhibit the production of host defense signaling molecules. However, mechanisms whereby C4/AC4 proteins are transported to chloroplasts are unknown. We report here that tomato (Solanum lycopersicum) COAT PROTEIN COMPLEX I (COPI) components play a critical role in redistributing Tomato yellow leaf curl virus C4 protein to chloroplasts via an interaction between the C4 and ß subunits of COPI. Coexpression of both proteins promotes the enrichment of C4 in chloroplasts that is blocked by a COPI inhibitor. Overexpressing or downregulating gene expression of COPI components promotes or inhibits the viral infection, respectively, suggesting a proviral role of COPI components. COPI components play similar roles in C4/AC4 transport and infections of two other geminiviruses: Beet curly top virus and East African cassava mosaic virus. Our results reveal an unconventional role of COPI components in protein trafficking to chloroplasts during geminivirus infection and suggest a broad-spectrum antiviral strategy in controlling geminivirus infections in plants.

DEAD/H-box helicase 11 is transcriptionally activated by Yin Yang-1 and accelerates oral squamous cell carcinoma progression.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H-box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC-4 and CAL-27 cells expressing doxycycline-inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang-1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K-AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor-promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment.

Multiparametric Characterization of Focal Cortical Dysplasia Using 3D MR Fingerprinting.

OBJECTIVES: To develop a multiparametric machine-learning (ML) framework using high-resolution 3 dimensional (3D) magnetic resonance (MR) fingerprinting (MRF) data for quantitative characterization of focal cortical dysplasia (FCD). MATERIALS: We included 119 subjects, 33 patients with focal epilepsy and histopathologically confirmed FCD, 60 age- and gender-matched healthy controls (HCs), and 26 disease controls (DCs). Subjects underwent whole-brain 3 Tesla MRF acquisition, the reconstruction of which generated T1 and T2 relaxometry maps. A 3D region of interest was manually created for each lesion, and z-score normalization using HC data was performed. We conducted 2D classification with ensemble models using MRF T1 and T2 mean and standard deviation from gray matter and white matter for FCD versus controls. Subtype classification additionally incorporated entropy and uniformity of MRF metrics, as well as morphometric features from the morphometric analysis program (MAP). We translated 2D results to individual probabilities using the percentage of slices above an adaptive threshold. These probabilities and clinical variables were input into a support vector machine for individual-level classification. Fivefold cross-validation was performed and performance metrics were reported using receiver-operating-characteristic-curve analyses. RESULTS: FCD versus HC classification yielded mean sensitivity, specificity, and accuracy of 0.945, 0.980, and 0.962, respectively; FCD versus DC classification achieved 0.918, 0.965, and 0.939. In comparison, visual review of the clinical magnetic resonance imaging (MRI) detected 48% (16/33) of the lesions by official radiology report. In the subgroup where both clinical MRI and MAP were negative, the MRF-ML models correctly distinguished FCD patients from HCs and DCs in 98.3% of cross-validation trials for the magnetic resonance imaging negative group and MAP negative group. Type II versus non-type-II classification exhibited mean sensitivity, specificity, and accuracy of 0.835, 0.823, and 0.83, respectively; type IIa versus IIb classification showed 0.85, 0.9, and 0.87. In comparison, the transmantle sign was present in 58% (7/12) of the IIb cases. INTERPRETATION: The MRF-ML framework presented in this study demonstrated strong efficacy in noninvasively classifying FCD from normal cortex and distinguishing FCD subtypes. ANN NEUROL 2024.

Impact of uniaxial cyclic stretching on matrix-associated endothelial cell responses.

Uniaxial cyclic stretching plays a pivotal role in the fields of tissue engineering and regenerative medicine, influencing cell behaviors and functionality based on physical properties, including matrix morphology and mechanical stimuli. This study delves into the response of endothelial cells to uniaxial cyclic strain within the geometric constraints of micro-nano fibers. Various structural scaffold forms of poly(l-lactide-co-caprolactone) (PLCL), such as flat membranes, randomly oriented fiber membranes, and aligned fiber membranes, were fabricated through solvent casting and electrospinning methods. Our investigation focuses on the morphological variation of endothelial cells under diverse geometric constraints and the mechanical-dependent release of nitric oxide (NO) on oriented fibrous membranes. Our results indicate that while uniaxial cyclic stretching promotes endothelial cell spreading, the anisotropy of the matrix morphology remains the primary driving factor for cell alignment. Additionally, uniaxial cyclic stretching significantly enhances NO release, with a notably stronger effect correlated to the increasing strain amplitude. Importantly, this study reveals that uniaxial cyclic stretching enhances the mRNA expression of key proteins, including talin, vinculin, rac, and nitric oxide synthase (eNOS).

Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of Epigenetic Regulators.

Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) allows for the identification of genomic targeting of DNA-binding proteins. Cleavage Under Targets and Release Using Nuclease (CUT&RUN) modifies this process by including a nuclease to digest DNA around a protein of interest. The result is a higher signal-to-noise ratio and decreased required starting material. This allows for high-fidelity sequence identification from as few as 500 cells, enabling chromatin profiling of precious tissue samples or primary cell types, as well as less abundant chromatin-binding proteins: all at significantly increased throughput.

The Impact of Social Support on Depressive Symptoms Through Mindfulness and Resilience Among Chinese Parents Who Lost Their Only Child.

The number of Shidu parents (parents over the age of 45 years who have lost their only child) has been increasing in China, which is important because Shidu parents experience depressive symptoms. This study investigated the potential mediating roles of mindfulness and resilience in the relation between social support and depressive symptoms among Shidu parents. From June to December 2021, 111 Shidu parents in Baoji city, China, completed a web-based survey on social support, depressive symptoms, mindfulness, and resilience. The results indicated that Shidu parents suffer from a high risk of depressive symptoms, and significant correlations were found between the study variables. Path analysis models showed that the relation between social support and depressive symptoms in Shidu parents was fully mediated by a combination of mindfulness and resilience. These findings further highlighted the significance of social support, mindfulness, and resilience in potentially alleviating depressive symptoms among Shidu parents.

Systematic conservation planning considering ecosystem services can optimize the conservation system in the Qinling-Daba Mountains.

Protected area are the cornerstone of biodiversity and ecosystem service conservation at the local, regional, and global levels. In 2019, China proposed the establishment of a nature reserve system (NRS)centered on national parks, integrating and improving various existing protected areas. This study focuses on the Qinling‒Daba Mountains, an area crucial for both biodiversity and ecosystem services. Through assessments of carbon storage (CS), water yield (WY), soil conservation (SC), and habitat quality (HQ), different conservation scenarios are considered in the context of Systematic conservation planning (SCP). An optimization scheme for the NRS in the Qinling-Daba Mountains is proposed, incorporating ecosystem services and comparing them with the existing system. Research indicates that the main protected areas are concentrated in the Min Mountain‒Motian Mountain‒Longmen Mountain region, the central Qinling region, and the Shennongjia‒Daba Mountain region. Compared with the original system, the area of protected regions in the NRS expanded by 52,000 km2 after the SCP scheme was incorporated. The number of patches decreased to 50, and the patch density reduced from 2.1 × 10-4(/100 ha) to 1.7 × 10-4(/100 ha), thereby reducing the fragmentation of the conservation system. Additionally, the optimized scheme achieved a conservation ratio of over 30% for CS, WY, SC, and HQ, with the conservation efficiency for WY and HQ increasing by 0.18 and 0.22, respectively. The study results provide support for optimizing the Qinling-Daba Mountains NRS and offer a reference for constructing NRSs in other regions. Considering ecosystem services in the optimization of the NRS helps enhance the supply capacity of ecological products, maintain national ecological security, and achieve harmonious coexistence and sustainable development between humans and nature.

Mechanical properties and water vapour corrosion behaviour of Al x CoCrFeNi high-entropy alloys.

Al x CoCrFeNi (x = 0.1, 0.5 and 1) high-entropy alloys (HEAs) were prepared using a spark plasma sintering (SPS) technique combined with aerosol powder. Their microstructure and phase constituents were characterized using an X-ray diffractometer and SEM, and their tensile properties, hardness and compactness were tested. The results show that the crystal structure of the Al x CoCrFeNi HEAs changed significantly with the Al content, from the original single face-centered cubic FCC phase (Al0.1CoCrFeNi) to an FCC + BCC structure (Al0.5CoCrFeNi), and then to FCC + BCC + sigma (σ) phase structures (AlCoCrFeNi). Chemical composition analysis showed that the crystal structure transformation was related to the segregation caused by the increased Al content. The hardness of the Al x CoCrFeNi HEAs increases with increasing Al content, and the hardness of AlCoCrFeNi reaches a maximum of 507.3 HV. The tensile properties of the alloy show a trend of first increasing and then decreasing with increasing Al content, and the yield strength, ultimate tensile strength and elongation of the Al0.5CoCrFeNi alloy reach maximum values of 527.4 MP, 943.3 MPa and 28.2%, respectively. The fracture mechanism of the Al0.1CoCrFeNi and Al0.5CoCrFeNi alloys is typical ductile fracture, while that of the AlCoCrFeNi alloy is cleavage fracture. The compactness of the alloy increases with the Al content. The samples were also subjected to high-temperature water vapour corrosion, and corrosion products such as Al3Fe5O12, CoCr2O4 and NiCr2O4 were found in the Al0.1 and Al0.5 alloys, whereas no oxide peaks were detected using XRD for the Al1 alloy. It was also presumed that a very thin alumina film was generated on the surface of the Al1 alloy, preventing the oxidation of the sample, in combination with the analysis of SEM, EDS and XPS behaviour.

Mo-Doped LaFeO3 Gas Sensors with Enhanced Sensing Performance for Triethylamine Gas.

Triethylamine is a common volatile organic compound (VOC) that plays an important role in areas such as organic solvents, chemical industries, dyestuffs, and leather treatments. However, exposure to triethylamine atmosphere can pose a serious threat to human health. In this study, gas-sensing semiconductor materials of LaFeO3 nano materials with different Mo-doping ratios were synthesized by the sol-gel method. The crystal structures, micro morphologies, and surface states of the prepared samples were characterized by XRD, SEM, and XPS, respectively. The gas-sensing tests showed that the Mo doping enhanced the gas-sensing performance of LaFeO3. Especially, the 4% Mo-doped LaFeO3 exhibited the highest response towards triethylamine (TEA) gas, a value approximately 11 times greater than that of pure LaFeO3. Meantime, the 4% Mo-doped LaFeO3 sensor showed a remarkably robust linear correlation between the response and the concentration (R2 = 0.99736). In addition, the selectivity, stability, response/recovery time, and moisture-proof properties were evaluated. Finally, the gas-sensing mechanism is discussed. This study provides an idea for exploring a new type of efficient and low-cost metal-doped LaFeO3 sensor to monitor the concentration of triethylamine gas for the purpose of safeguarding human health and safety.

Fast, Zero-Reference Low-Light Image Enhancement with Camera Response Model.

Low-light images are prevalent in intelligent monitoring and many other applications, with low brightness hindering further processing. Although low-light image enhancement can reduce the influence of such problems, current methods often involve a complex network structure or many iterations, which are not conducive to their efficiency. This paper proposes a Zero-Reference Camera Response Network using a camera response model to achieve efficient enhancement for arbitrary low-light images. A double-layer parameter-generating network with a streamlined structure is established to extract the exposure ratio K from the radiation map, which is obtained by inverting the input through a camera response function. Then, K is used as the parameter of a brightness transformation function for one transformation on the low-light image to realize enhancement. In addition, a contrast-preserving brightness loss and an edge-preserving smoothness loss are designed without the requirement for references from the dataset. Both can further retain some key information in the inputs to improve precision. The enhancement is simplified and can reach more than twice the speed of similar methods. Extensive experiments on several LLIE datasets and the DARK FACE face detection dataset fully demonstrate our method's advantages, both subjectively and objectively.

Impact of osteopenia and osteosarcopenia on the outcomes after surgery of hepatobiliary-pancreatic cancers.

Objective: The purpose of this study is to investigate potential associations between osteopenia, osteosarcopenia, and postoperative outcomes in patients with hepatobiliary-pancreatic cancer (HBPC). Methods: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between osteopenia, osteosarcopenia, and outcomes of surgical treatment of HBPC patients from the start of each database to September 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Results: This analysis included a total of 16 articles with a combined patient cohort of 2,599 individuals. The results demonstrated that HBPC patients with osteopenia had significantly inferior OS (HR: 2.27, 95% CI: 1.70-3.03, p < 0.001) and RFS (HR: 1.96, 95% CI: 1.42-2.71, p < 0.001) compared to those without osteopenia. Subgroup analysis demonstrated that these findings were consistent across univariate and multivariate analyses, as well as hepatocellular carcinoma, biliary tract cancer, and pancreatic cancer. The risk of postoperative major complications was significantly higher in patients with osteopenia compared to those without osteopenia (OR: 1.66, 95% CI: 1.19-2.33, p < 0.001). Besides, we also found that the presence of osteosarcopenia in HBPC patients was significantly related to poorer OS (HR: 3.31, 95% CI: 2.00-5.48, p < 0.001) and PFS (HR: 2.50, 95% CI: 1.62-3.84, p < 0.001) in comparison to those without osteosarcopenia. Conclusion: Preoperative osteopenia and osteosarcopenia can predict poorer OS and RFS with HBPC after surgery.

Dual-mode detection of glucose based on pistol-like DNAzyme-mediated exonuclease-assisted signal cycle.

Detecting glucose accurately and sensitively from clinical samples like tears and saliva is still difficult. We have created a sensor that can detect glucose with high sensitivity and accuracy by combining the use of glucose oxidase (GOx) to catalyze glucose, a pistol-like DNAzyme (PLDz) to transform the signal, gold nanoparticles (AuNPs) to enhance the optical properties and the exonuclease-III (Exo-III) to amplify the signal. As a result, the proposed method exhibits a low detection limit of 7.5 pM and a wide detection range covering seven orders of magnitude. The suggested dual-mode strategy provides a sensitive, precise and specific detection method for glucose. Another advantage is that the dual-mode technique significantly improves the precision and consistency of the measurements, demonstrating its immense potential for use in biomedical research and clinical diagnostics.

[Box: see text].

CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Exposure-Response Modeling in Adults and Adolescents With Schizophrenia to Support the Extrapolation of Brexpiprazole Efficacy to Adolescents.

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence-based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady-state concentration)-response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure-response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease-drug-dropout models were developed using patient-level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure-response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure-response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13-17 years with schizophrenia.

Aptamer-Functionalized Magnetic Ti3C2 Based Nanoplatform for Simultaneous Enrichment and Detection of Exosomes.

Exosomes are nanovesicles secreted by cells, which play a crucial role in various pathological processes. Exosomes have shown great promise as tumor biomarkers because of the abundant secretion during tumor formation. The development of a convenient, efficient, and cost-effective method for simultaneously enriching and detecting exosomes is of utmost importance for both basic research and clinical applications. In this study, an aptamer-functionalized magnetic Ti3C2 composite material (Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA) is prepared for the simultaneous enrichment and detection of exosomes. CD63 aptamers are utilized to recognize and capture the exosomes, followed by magnetic separation. The exosomes are then released by cleaving the disulfide bonds of DSP. Compared to traditional methods, Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA exhibited superior efficiency in enriching exosomes while preserving their structural and functional integrity. Detection of exosome concentration is achieved through the fluorescence quenching of Ti3C2 and the competitive binding between the exosomes and a fluorescently labeled probe. This method exhibited a low detection limit of 4.21 × 104 particles mL-1, a number that is comparable to the state-of-the-art method in the detection of exosomes. The present study demonstrates a method of simultaneous enrichment and detection of exosomes with a high sensitivity, accuracy, specificity, and cost-effectiveness providing significant potential for clinical research and diagnosis.

Procaine induces cell cycle arrest, apoptosis and autophagy through the inhibition of the PI3K/AKT and ERK pathways in human tongue squamous cell carcinoma.

Procaine (PCA), a local anesthetic commonly used in stomatology, exhibits antitumor activity in some human malignancies. However, the precise mechanism underlying PCA activity remains unknown, and its antitumor effect in human tongue squamous carcinoma cells has not been reported. Flow cytometry and western blotting were used to assess the effects of PCA on mitochondrial membrane potential (ΔΨm), intracellular reactive oxygen species (ROS) production, cell cycle and apoptosis. The results suggested that PCA inhibits CAL27 and SCC-15 cell proliferation, and clone formation in a dose-dependent manner. CAL27 cells were more sensitive to PCA than SCC-15 cells. PCA also significantly inhibited cell migration, induced mitochondrial damage, reduced ΔΨm and increased intracellular ROS production. PCA causes G2/M cycle arrest and induces apoptosis. The possible mechanism for the inhibition of human tongue squamous carcinoma cell proliferation is through the regulation of ERK phosphorylation and PI3K/AKT-mediated signaling pathways. The results further suggested that autophagy occurs during PCA-induced apoptosis in CAL27 cells, and the addition of the autophagy inhibitor hydroxychloroquine sulfate further enhanced the sensitivity of PCA to inhibit cell proliferation, indicating that autophagy plays an important role in protecting cancer cells from apoptosis. PCA shows potential as an anticancer drug and its combination with autophagy inhibitors enhances its sensitivity.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma.

BACKGROUND: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.