Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery.

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.

Quantitative parameters of dual-layer spectral detector computed tomography for evaluating differentiation grade and lymphovascular and perineural invasion in colorectal adenocarcinoma.

PURPOSE: To explore the predictive value of dual-layer spectral detector CT (SDCT) quantitative parameters for determining differentiation grade, lymphovascular invasion (LVI) and perineural invasion (PNI) in colorectal adenocarcinoma (CRAC) patients. METHODS: A total of 106 eligible patients with CRAC were included in this study. Spectral parameters, including CT values at 40 and 100 keV, the effective atomic number (Zeff), the iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and the normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP), were compared according to the differentiation grade and the status of LVI and PNI. The diagnostic accuracies of the quantitative parameters with statistical significance were determined via receiver operating characteristic (ROC) curves, and the area under the curve (AUC) was calculated. RESULTS: There were 57 males and 49 females aged 43-86 (69 ± 10) years. The measured values of the spectral quantitative parameters of the CRAC were consistent within the observer (ICC range: 0.800-0.926). The 40 keV-AP, IC-AP, NIC-AP, 40 keV-VP, and IC-VP were significantly different among the different differentiation grades in the CRAC (P = 0.040, AUC = 0.673; P = 0.035, AUC = 0.684; P = 0.031, AUC = 0.639; P = 0.044, AUC = 0.663 and P = 0.035, AUC = 0.666, respectively). A statistically significant difference was observed in 40 keV-VP, 100 keV-VP, Zeff-VP, IC-VP, and λHU-VP between LVI-positive and LVI-negative patients (P = 0.003, AUC = 0.688; P = 0.015, AUC = 0.644; P = 0.001, AUC = 0.688; P = 0.001, AUC = 0.703 and P = 0.003, AUC = 0.677, respectively). There were no statistically significant differences in the values of the spectral parameters of the PNI state of patients with CRAC (P > 0.05). CONCLUSION: The quantitative parameters of SDCT had good diagnostic efficacy in differentiating between different grades and statuses of LVI in patients with CRAC; however, SDCT did not have value for identifying the state of PNI.

Improving ranging performance of SiPM LiDAR in low SNR conditions through an echo processing method and laser pulse modulation.

Due to its numerous advantages such as high gain and low operating bias, the silicon photomultiplier (SiPM) holds great potential in LiDAR applications. However, it is more jittery at weak echoes and more sensitive to ambient light, making its ranging performance at low signal-to-noise ratios (SNRs) severely deteriorated. To enhance the ranging performance of SiPM LiDAR under low SNR, a novel echo processing method, to the best of our knowledge, was proposed based on the statistical property of SiPM responses and validated under relatively intensive sunlight (>50k l x) using a self-developed LiDAR system. At the same time, laser pulse width modulation and multi-pulse laser emission are used in ranging experiments to maximize the advantages of this method. It has shown that increasing the laser pulse width within a certain range can improve ranging performance, and that emitting multiple laser pulses improves ranging performance more significantly. Utilizing a three-pulse laser with a peak power of only 3.2 W, a target 122 m away was ranged with a precision of 6.53 cm with only five accumulations.

Precision and Accuracy of Single-Cell/Nuclei RNA Sequencing Data.

Single-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue is the quality of sc/snRNA-Seq data that would impact the reliability of downstream analyses. Here we evaluated the precision and accuracy in 18 sc/snRNA-Seq datasets. The precision was assessed on data from human brain studies with a total of 3,483,905 cells from 297 individuals, by utilizing technical replicates. The accuracy was evaluated with sample-matched scRNA-Seq and pooled-cell RNA-Seq data of cultured mononuclear phagocytes from four species. The results revealed low precision and accuracy at the single-cell level across all evaluated data. Cell number and RNA quality were highlighted as two key factors determining the expression precision, accuracy, and reproducibility of differential expression analysis in sc/snRNA-Seq. This study underscores the necessity of sequencing enough high-quality cells per cell type per individual, preferably in the hundreds, to mitigate noise in expression quantification.

Assessing the influence of parameters on tissue welding in small bowel end-to-end anastomosis in vitro and in vivo.

BACKGROUND: The use of high-frequency electric welding technology for intestinal end-to-end anastomosis holds significant promise. Past studies have focused on in vitro, and the safety and efficacy of this technology is uncertain, severely limiting the clinical application of this technology. This study investigates the impact of compression pressure, energy dosage, and duration on anastomotic quality using a homemade anastomosis device in both in vitro and in vivo settings. METHODS: Two hundred eighty intestines and 5 experimental pigs were used for in vitro and in vivo experiments, respectively. The in vitro experiments were conducted to study the effects of initial pressure (50-400 kpa), voltage (40-60 V), and time (10-20 s) on burst pressure, breaking strength, thermal damage, and histopathological microstructure of the anastomosis. Optimal parameters were then inlaid into a homemade anastomosis and used for in vivo experiments to study the postoperative porcine survival rate and the pathological structure of the tissues at the anastomosis and the characteristics of the collagen fibers. RESULTS: The anastomotic strength was highest when the compression pressure was 250 kPa, the voltage was 60 V, and the time was 15 s. The degree of thermal damage to the surrounding tissues was the lowest. The experimental pigs had no adverse reactions after the operation, and the survival rate was 100%. 30 days after the operation, the surgical site healed well, and the tissues at the anastomosis changed from immediate adhesions to permanent connections. CONCLUSION: High-frequency electric welding technology has a certain degree of safety and effectiveness. It has the potential to replace the stapler anastomosis in future and become the next generation of new anastomosis device.

The decreased astrocyte-microglia interaction reflects the early characteristics of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aß is a typical AD hall marker, but Aß-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aß-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aß-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.

[Value of CT Quantitative Parameters in Prediction of Pathological Types
of Lung Ground Glass Nodules].

BACKGROUND: The pathological types of lung ground glass nodules (GGNs) show great significance to the clinical treatment. This study was aimed to predict pathological types of GGNs based on computed tomography (CT) quantitative parameters. METHODS: 389 GGNs confirmed by postoperative pathology were selected, including 138 cases of precursor glandular lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], 109 cases of microinvasive adenocarcinoma (MIA) and 142 cases of invasive adenocarcinoma (IAC). The morphological characteristics of nodules were evaluated subjectively by radiologist, as well as artificial intelligence (AI). RESULTS: In the subjective CT signs, the maximum diameter of nodule and the frequency of spiculation, lobulation and pleural traction increased from AAH+AIS, MIA to IAC. In the AI quantitative parameters, parameters related to size and CT value, proportion of solid component, energy and entropy increased from AAH+AIS, MIA to IAC. There was no significant difference between AI quantitative parameters and the subjective CT signs for distinguishing the pathological types of GGNs. CONCLUSIONS: AI quantitative parameters were valuable in distinguishing the pathological types of GGNs.

Co-Analysis of Serum and Urine Differentially Expressed Proteins in Mucopolysaccharidosis Type I.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by the deficiency of the enzyme α-l-iduronidase (IDUA), typically leading to devastating secondary pathophysiological cascades. Due to the irreversible nature of the disease's progression, early diagnosis and interventional treatment has become particularly crucial. Considering the fact that serum and urine are the most commonly used specimens in clinical practice for detection, we conducted an analysis to identify the differential protein profile in the serum and urine of MPS I patients using the tandem mass tag (TMT) technique. A total of 182 differentially expressed proteins (DEPs) were detected in serum, among which 9 showed significant differences as confirmed by parallel reaction monitoring (PRM) analysis. The proteins APOA1 and LGFBP3 were downregulated in serum, while the expression levels of ALDOB, CD163, CRTAC1, DPP4, LAMP2, SHBG, and SPP2 exhibited an increase. In further exploratory studies of urinary proteomics, 32 identified DEPs were consistent with the discovered findings in serum tests, specifically displaying a high diagnostic area under the curve (AUC) value. Thus, our study demonstrates the value of serum-urine integrated proteomic analysis in evaluating the clinical course of MPS I and other potential metabolic disorders, shedding light on the importance of early detection and intervention in these conditions.

Quantitative parameters of dual-layer spectral detector computed tomography for evaluating Ki-67 and human epidermal growth factor receptor 2 expression in colorectal adenocarcinoma.

Background: Ki-67 and human epidermal growth factor receptor 2 (HER2) are key biomarkers in evaluating the prognosis of colorectal adenocarcinoma (CRAC). The purpose of this study was to investigate the value of quantitative parameters in dual-layer spectral detector computed tomography (SDCT) for evaluating the expression of Ki-67 and HER2 in CRAC. Methods: In this retrospective, cross-sectional study, 88 eligible patients with pathologically confirmed CRAC were selected from Taicang Hospital of Traditional Chinese Medicine between May 2021 and April 2023. The study participants underwent enhanced SDCT of the whole abdomen within 2 weeks before to surgery, did not receive antitumor therapy, and had complete immunohistochemical (IHC) indexes. Patients with nonadenocarcinoma pathologic types, poor quality of spectral CT images, or no complete immunohistochemistry results were excluded. Spectral parameters including CT values at 40 and 100 keV, effective atomic number, iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP) were analyzed for their value in distinguishing between the high and low expression of Ki-67 and HER2-positive and -negative status in CRAC. The statistical significance of the SDCT parameters between the different groups of Ki-67 expression and those of HER2 status was assessed with the Mann-Whitney test. Spearman correlation analysis was used to analyze the correlation between the SDCT parameters and the extent of Ki-67 expression and HER2 expression status. The receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was calculated. Results: The SDCT parameters of CT values at 40 keV, effective atomic number, IC, and the λHU in the VP showed significant differences between the Ki-67 high- and low-expression groups in CRAC (P=0.035, P=0.041, P=0.036, and P=0.044, respectively), with AUCs of 0.639 [95% confidence interval (CI): 0.512-0.766], 0.634 (95% CI: 0.508-0.761), 0.638 (95% CI: 0.510-0.766), and 0.633 (95% CI: 0.504-0.762), respectively. The expression of CRAC Ki-67 was positively correlated with CT values at 40 keV (r=0.227; P=0.034), effective atomic number (r=0.219; P=0.040), IC (r=0.225; P=0.035), and the λHU in VP (r=0.216; P=0.043). SDCT parameter values showed no statistical difference between negative and positive expression in HER2 (all P values >0.05). There was no significant correlation between SDCT parameters and the expression of HER2 in CRAC (all P values >0.05). Conclusions: The quantitative parameters of SDCT in the VP provide valuable information for distinguishing between the low expression and high expression of Ki-67 in CRAC.

The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling During Neurodevelopment.

Intellectual disability (ID) is a condition characterized by cognitive impairment and difficulties in adaptive functioning. In our research, we identified two de novo mutations (c.955C>T and c.732C>A) at the KDM2A locus in individuals with varying degrees of ID. In addition, by using the Gene4Denovo database, we discovered five additional cases of de novo mutations in KDM2A. The mutations we identified significantly decreased the expression of the KDM2A protein. To investigate the role of KDM2A in neural development, we used both 2D neural stem cell models and 3D cerebral organoids. Our findings demonstrated that the reduced expression of KDM2A impairs the proliferation of neural progenitor cells (NPCs), increases apoptosis, induces premature neuronal differentiation, and affects synapse maturation. Through ChIP-Seq analysis, we found that KDM2A exhibited binding to the transcription start site regions of genes involved in neurogenesis. In addition, the knockdown of KDM2A hindered H3K36me2 binding to the downstream regulatory elements of genes. By integrating ChIP-Seq and RNA-Seq data, we made a significant discovery of the core genes' remarkable enrichment in the MAPK signaling pathway. Importantly, this enrichment was specifically linked to the p38 MAPK pathway. Furthermore, disease enrichment analysis linked the differentially-expressed genes identified from RNA-Seq of NPCs and cerebral organoids to neurodevelopmental disorders such as ID, autism spectrum disorder, and schizophrenia. Overall, our findings suggest that KDM2A plays a crucial role in regulating the H3K36me2 modification of downstream genes, thereby modulating the MAPK signaling pathway and potentially impacting early brain development.

Glioblastoma behavior study under different frequency electromagnetic field.

The tumor-treating fields (TTFields) technology has revolutionized the management of recurrent and newly diagnosed glioblastoma (GBM) cases. To ameliorate this treatment modality for GBM and other oncological conditions, it is necessary to understand the biophysical principles of TTFields better. In this study, we further analyzed the mechanism of the electromagnetic exposure with varying frequencies and electric field strengths on cells in mitosis, specifically in telophase. In reference to previous studies, an intuitive finite element model of the mitotic cell was built for electromagnetic simulations, predicting a local increase in the cleavage furrow region, which may help explain TTFields' anti-proliferative effects. Cell experiments confirmed that the reduction in proliferation and migration of glioma cell by TTFields was in a frequency- and field-strength-dependent manner. This work provides unique insights into the selection of frequencies in the anti-proliferative effect of TTFields on tumors, which could improve the application of TTFields.

The role of computed tomography in enterolith causing small bowel obstruction: A case series.

Intestinal obstruction caused by enteroliths is an uncommon medical condition. Timely detection of the presence of enteroliths and identification of their origin can guide clinical treatment. This study aimed to present the Computed Tomography (CT) features of enterolithic ileus confirmed by surgery in 7 patients. Seven patients with surgically confirmed enterolithic ileus who were admitted to our hospital between December 2013 and December 2022 were continuously enrolled, and an abdominopelvic CT examination was performed before surgery. The imaging characteristics were then analyzed. In the transition zone of all patients with intestinal obstruction, the sharply defined intraluminal masses were found. Three of them had gallstones and 4 had primary enteroliths. All 5 enteroliths in the 4 patients with primary enteroliths were in the proximal small intestine and were low-density with gas. Additionally, 3 gallstones were present in the distal small bowel, and calcifications were observed. Simultaneously, cholecystitis and secondary cholecystoduodenal fistula were observed in all 3 patients with gallstones. Compared to gallstones, primary enteroliths tend to be higher positioned, less dense, and accompanied by gas. CT examination is very important, as it allows accurate identification, location, diagnosis, and identification of complications of the different types of enteroliths to provide a basis for surgery.

Effects of Damage to the Integrity of the Left Dual-Stream Frontotemporal Network Mediated by the Arcuate Fasciculus and Uncinate Fasciculus on Acute/Subacute Post-Stroke Aphasia.

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone.

The diagnosis performance of convolutional neural network in the detection of pulmonary nodules: a systematic review and meta-analysis.

BACKGROUND: Pulmonary nodules are an early imaging indication of lung cancer, and early detection of pulmonary nodules can improve the prognosis of lung cancer. As one of the applications of machine learning, the convolutional neural network (CNN) applied to computed tomography (CT) imaging data improves the accuracy of diagnosis, but the results could be more consistent. PURPOSE: To evaluate the diagnostic performance of CNN in assisting in detecting pulmonary nodules in CT images. MATERIAL AND METHODS: PubMed, Cochrane Library, Web of Science, Elsevier, CNKI and Wanfang databases were systematically retrieved before 30 April 2023. Two reviewers searched and checked the full text of articles that might meet the criteria. The reference criteria are joint diagnoses by experienced physicians. The pooled sensitivity, specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated by a random-effects model. Meta-regression analysis was performed to explore potential sources of heterogeneity. RESULTS: Twenty-six studies were included in this meta-analysis, involving 2,391,702 regions of interest, comprising segmented images with a few wide pixels. The combined sensitivity and specificity values of the CNN model in detecting pulmonary nodules were 0.93 and 0.95, respectively. The pooled diagnostic odds ratio was 291. The AUC was 0.98. There was heterogeneity in sensitivity and specificity among the studies. The results suggested that data sources, pretreatment methods, reconstruction slice thickness, population source and locality might contribute to the heterogeneity of these eligible studies. CONCLUSION: The CNN model can be a valuable diagnostic tool with high accuracy in detecting pulmonary nodules.

A new diagnostic tool for brain disorders: extracellular vesicles derived from neuron, astrocyte, and oligodendrocyte.

Brain disorders are the leading cause of disability worldwide, affecting people's quality of life and causing economic burdens. The current clinical diagnosis of brain disorders relies solely on individual phenotypes and lacks accurate molecular biomarkers. An emerging field of research centers around extracellular vesicles (EVs), nanoscale membrane vesicles which can easily cross the blood-brain barrier. EVs in the blood are derived from various tissues, including the brain. Therefore, purifying central nervous system (CNS)-derived EVs from the blood and analyzing their contents may be a relatively non-invasive way to analyze brain molecular alterations and identify biomarkers in brain disorders. Recently, methods for capturing neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in peripheral blood were reported. In this article, we provide an overview of the research history of EVs in the blood, specifically focusing on biomarker findings in six major brain disorders (Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, depression, and autism spectrum disorder). Additionally, we discuss the methodology employed for testing CNS-derived EVs. Among brain disorders, Alzheimer's disease has received the most extensive attention in EV research to date. Most studies focus on specific molecules, candidate proteins, or miRNAs. Notably, the most studied molecules implicated in the pathology of these diseases, such as Aß, tau, and α-synuclein, exhibit good reproducibility. These findings suggest that CNS-derived EVs can serve as valuable tools for observing brain molecular changes minimally invasively. However, further analysis is necessary to understand the cargo composition of these EVs and improve isolation methods. Therefore, research efforts should prioritize the analysis of CNS-derived EVs' origin and genome-wide biomarker discovery studies.

Prediction of postoperative recurrence in resectable pancreatic body/tail adenocarcinoma: a novel risk stratification approach using a CT-based nomogram.

OBJECTIVES: To identify prognostic CT features that predict recurrence in patients with resectable pancreatic body/tail adenocarcinoma (PBTA) and construct a CT-based nomogram for preoperative risk stratification. METHODS: A total of 258 patients with resectable PBTA who underwent upfront surgery were retrospectively enrolled (development cohort, n = 172; validation cohort, n = 86), and their clinical and CT features were analyzed. Stepwise Cox proportional hazard analysis was performed to identify prognostic features and construct a predictive nomogram for recurrence-free survival (RFS). The prognostic performance of the CT-based nomogram was validated and compared to the 8th American Joint Committee on Cancer (AJCC) pathological staging system. RESULTS: In the development cohort, the following five CT features for predicting recurrence were identified to construct the nomogram: tumor density in the venous phase, tumor necrosis, adjacent organ invasion, splenic vein invasion, and superior mesenteric vein/portal vein abutment. In the validation cohort, the CT-based nomogram showed a concordance index of 0.65 (95% confidence interval: 0.58-0.73), which was higher than the 8th AJCC staging system. The area under the curves of the nomogram for predicting recurrence at 0.5, 1, and 2 years were 0.66, 0.71, and 0.72, respectively. Patients were categorized into high- and low-risk groups with 1-year recurrence probabilities of 0.73 and 0.43, respectively. CONCLUSIONS: The proposed nomogram provided accurate recurrence risk stratification for patients with resectable PBTA in a preoperative setting and may be used to facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: The proposed CT-based nomogram, based on easily available CT features, may serve as an effective and convenient tool for stratifying further the recurrence risk of patients with pancreatic body/tail adenocarcinoma. KEY POINTS: • The CT-based nomogram, incorporating five commonly used CT features, successfully preoperatively stratified patients with resectable PBTA into distinct prognosis groups. • Tumor density in the venous phase, tumor necrosis, splenic vein invasion, adjacent organ invasion, and superior mesenteric vein/portal vein abutment were associated with RFS in patients with resectable PBTA. • The CT-based nomogram exhibited better predictive performance for recurrence than the 8th AJCC staging system.

Validation and optimization of two models for the magnetic restoring forces using a multi-stable piezoelectric energy harvester.

This article presents a tunable multi-stable piezoelectric energy harvester. The apparatus consists of a stationary magnet and a cantilever beam whose free end is attached by an assembly of two cylindrical magnets that can be moved along the beam and a small cylindrical magnet that is fixed at the beam tip. By varying two parameters, the system can assume three stability states: tri-stable, bi-stable, and mono-stable, respectively. The developed apparatus is used to validate two models for the magnetic restoring force: the equivalent magnetic point dipole approach and the equivalent magnetic 2-point dipole approach. The study focuses on comparing the accuracy of the two models for a wide range of the tuning parameters. The restoring forces of the apparatus are determined dynamically and compared with their analytical counterparts based on each of the models. To improve the model accuracy, a model optimization is carried out by using the multi-population genetic algorithm. With the optimum models, the parametric sensitivity of each of the models is investigated. The stability state region is generated by using the optimum second model.

An ex vivo preliminary investigation into the impact of parameters on tissue welding strength in small intestine mucosa-mucosa end-to-end anastomosis.

Background: Tissue welding is an electrosurgical technique that can fuse tissue for small intestine anastomosis. However, limited knowledge exists on its application in mucosa-mucosa end-to-end anastomosis. This study investigates the effects of initial compression pressure, out-put power, and duration time on anastomosis strength ex vivo in mucosa-mucosa end-to-end anastomosis. Methods: Ex vivo porcine bowel segments were used to create 140 mucosa-mucosa end-to-end fusions. Different experimental parameters were employed for fusion, including initial com-pression pressure (50kPa-400 kPa), output power (90W, 110W, and 140W), and fusion time (5, 10, 15, 20 s). The fusion quality was measured by burst pressure and optical microscopes. Results: The best fusion quality was achieved with an initial compressive pressure between 200 and 250 kPa, an output power of 140W, and a fusion time of 15 s. However, an increase in output power and duration time resulted in a wider range of thermal damage. There was no significant difference between the burst pressure at 15 and 20 s (p > 0.05). However, a substantial increase in thermal damage was observed with longer fusion times of 15 and 20 s (p < 0.05). Conclusion: The best fusion quality for mucosa-mucosa end-to-end anastomosis ex vivo is achieved when the initial compressive pressure is between 200 and 250 kPa, the output power is approximately 140W, and the fusion time is approximately 15 s. These findings can serve as a valuable theoretical foundation and technical guidance for conducting animal experiments in vivo and subsequent tissue regeneration.

Deep Bottom-up Proteomics Enabled by the Integration of Liquid-Phase Ion Trap.

In bottom-up proteomics, the complexity of the proteome requires advanced peptide separation and/or fractionation methods to acquire an in-depth understanding of protein profiles. Proposed earlier as a solution-phase ion manipulation device, liquid phase ion traps (LPITs) were used in front of mass spectrometers to accumulate target ions for improved detection sensitivity. In this work, an LPIT-reversed phase liquid chromatography-tandem mass spectrometry (LPIT-RPLC-MS/MS) platform was established for deep bottom-up proteomics. LPIT was used here as a robust and effective method for peptide fractionation, which also shows good reproducibility and sensitivity on both qualitative and quantitative levels. LPIT separates peptides based on their effective charges and hydrodynamic radii, which is orthogonal to that of RPLC. With excellent orthogonality, the integration of LPIT with RPLC-MS/MS could effectively increase the number of peptides and proteins being detected. When HeLa cells were analyzed, peptide and protein coverages were increased by ∼89.2% and 50.3%, respectively. With high efficiency and low cost, this LPIT-based peptide fraction method could potentially be used in routine deep bottom-up proteomics.

The diagnostic value of quantitative parameters on dual-layer detector-based spectral CT in identifying ischaemic stroke.

Objective: To investigate the diagnostic value of quantitative parameters of spectral computed tomography (CT) in ischaemic stroke areas. Methods: The medical records of 57 patients with acute ischaemic stroke (AIS) who underwent plain computed tomography (CT) head scans, CT angiography (CTA), and CT perfusion (CTP) were retrospectively reviewed. The ischaemic areas (including the core infarct area and penumbra) and non-ischaemic areas in each patient were quantitatively analyzed using F-STROKE software. Two independent readers measured the corresponding values of the spectroscopic quantitative parameters (effective atomic number [Zeff value], iodine density value, and iodine-no-water value) in the ischaemic area and contralateral normal area alone. The differences in spectroscopic quantitative parameters between the two groups were compared, and their diagnostic efficacy was obtained. Results: The Zeff, iodine-no-water value, and iodine density value of the ischaemic area all showed significant lower than those of non-ischaemic tissue (P < 0.001). For differentiating the ischaemic area from non-ischaemic tissue, the area under the curve (AUC) of the Zeff value reached 0.869 (cut-off value: 7.385; sensitivity: 93.0%; specificity: 70.2%), the AUC of the iodine density value reached 0.932 (cut-off value: 0.235; sensitivity: 91.2%; specificity: 82.5%), and the AUC of the iodine-no-water value reached 0.922 (cut-off value: 0.205; sensitivity: 96.5%; specificity: 78.9%). Conclusion: The study showed the spectral CT would be a potential novel rapid method for identifying AIS. The spectral CT quantitative parameters (Zeff, iodine density values, and iodine-no-water values) can effectively differentiate the ischaemic area from non-ischaemic tissue in stroke patients.