Protective role of fruits of Rosa odorata var. gigantea against WIRS-induced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis.

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy.

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

Biomechanical evaluation of reinsertion and revision screws in the subaxial cervical vertebrae.

BACKGROUND: This study aimed to evaluate the biomechanical effects of reinserted or revised subaxial cervical vertebral screws. METHODS: The first part aimed to gauge the maximum insertional torque (MIT) of 30 subaxial cervical vertebrae outfitted with 4.0-mm titanium screws. A reinsertion group was created wherein a screw was wholly removed and replaced along the same trajectory to test its maximum pullout strength (MPOS). A control group was also implemented. The second part involved implanting 4.0-mm titanium screws into 20 subaxial cervical vertebrae, testing them to failure, and then reinserting 4.5-mm revision screws along the same path to determine and compare the MIT and MPOS between the test and revision groups. RESULTS: Part I findings: No significant difference was observed in the initial insertion's maximum insertion torque (MIT) and maximum pull-out strength (MPOS) between the control and reinsertion groups. However, the MIT of the reinsertion group was substantially decreased compared to the first insertion. Moderate to high correlations were observed between the MIT and MPOS in both groups, as well as between the MIT of the first and second screw in the reinsertion group. Part II, the MIT and MPOS of the screw in the test group showed a strong correlation, while a modest correlation was observed for the revision screw used in failed cervical vertebrae screw. Additionally, the MPOS of the screw in the test group was significantly higher than that of the revision screw group. CONCLUSION: This study suggests that reinsertion of subaxial cervical vertebrae screws along the same trajectory is a viable option that does not significantly affect fixation stability. However, the use of 4.5-mm revision screws is inadequate for failed fixation cases with 4.0-mm cervical vertebral screws.

Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

Self-assembly formation of Co quantum dot loaded N-doped porous carbon cathode for quinoline degradation in the electro-Fenton system.

Quinoline is high toxicity and difficult biodegradation in oil washing wastewater. Therefore, efficient removal of quinoline contaminant from water bodies poses a major challenge. Hence, Co quantum dot loaded N-doped porous carbon (CoNC) nanosheets grown in situ on carbon cloth were fabricated as cathode for the degradation of quinoline in electro-Fenton system. Under optimal conditions (c(Fe2+) = 0.5 mM, U = -0.3 V, pH = 3), quinoline was completely degraded within 15 min with superior apparent rate constant of 0.385 min-1, which was 19.6 times higher than that of the ZIF-L precursor, due to the abundance of Co QDs active sites and hydrophilicity and electrical conductivity of N-doped porous carbon. In addition, three reaction pathways for quinoline were deduced by combining Density Functional Theory (DFT) calculation and Liquid Chromatography-Mass Spectrometry (LC-MS). More importantly, in situ FTIR and free energy calculations were analyzed to reveal that pathway Ⅰ as spontaneous reaction was the main reaction pathway. Finally, the toxicity of the intermediates was assessed with ECOSAR software and E. coli experiments, and the overall toxicity decreased during the degradation reactions. This work provides novel perspectives on environmental protection by designing in-situ grown cathodes through self-assembly method, thereby effectively purifying pollutants from wastewater.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Combined EEG-tDCS approach in resting state to reduce comorbid anxiety and depressive symptoms in affective disorders: A sham-controlled pilot study.

Continuous challenges have been imposed on mental health science by Anxiety and Depression disorders as the most prevalent and debilitating psychiatric conditions worldwide. Pharmacologic and cognitive behavioral therapies, either alone or in combination, have been considered as the first-line therapies, however, resistant symptomatology is prevalent in comorbid conditions with symptoms remaining after interventions. The demand for new therapeutic solutions has given space to the development of non-invasive brain stimulation techniques (NIBS), and the transmagnetic direct current stimulation (tDCS) has been reported as a safe and well-tolerated technique for the treatment of several mental health conditions, including Anxiety and Depression disorders. Relying on quantitative electroencephalography(qEEG)- tDCS approach, the current study aims to inspect the effect of tDCS intervention on patients who suffer from anxiety-depression comorbidity, in particular, the impact of tDCS intervention on qEEG spectral power activity and resting-state connectivity organization during eyes closed and eyes open protocols. QEEG data were acquired from eight patients suffering from moderate to severe anxiety-depression comorbid symptoms along with poor coping skills to manage stress and negative affect. Twelve control subjects allocated in the control group exhibiting low to moderate symptoms in both anxiety and depression conditions went also through the qEEG data acquisition. In addition, a sham-controlled study was conducted, and the patient group went through resting-state qEEG-tDCS neuromodulation once a week for ten weeks. Various-stage qEEG recordings were performed to inspect the efficacy of tDCS treatment during the modulation of brain regions involved in the regulation of affective responses. Our results demonstrated that after tDCS neuromodulation, the patients' groups exhibited decreased absolute power abnormalities over the left anterior cingulate cortex and reduced abnormal activity in the alpha band over posterior regions; improved functional connectivity indexes; decreased anxiety and depressive scores while positive affect score was improved. Besides the promising improvements, our study did not find a significant tDCS effect on perceived stress and negative affect scores. Consistently, significant differences in absolute spectral power over the left anterior cingulate cortex were detected among the patient group, as compared to the controls, as expected. Therefore, our study offers preliminary data to understand the neuroplasticity changes that potentially result from the manipulation of cortical excitability during affective regulation protocols followed by the consequent decrease of comorbid anxiety and depressive symptomatology. The pilot study was followed by prospective registration with ChiCTR2200062142.

SPINK4 modulates inhibition of glycolysis against colorectal cancer progression.

Dysregulation of glycolysis is frequently linked to aggressive tumor activity in colorectal cancer (CRC). Although serine peptidase inhibitor, Kazal type 4 (SPINK4) has been linked to CRC, its exact linkage to glycolytic processes and gene expression remains unclear. Differentially expressed genes (DEGs) were screened from two CRC-related datasets (GSE32323 and GSE141174), followed by expression and prognostic analysis of SPINK4. In vitro techniques such as flow cytometry, western blotting, transwell assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess SPINK4 expression in CRC cells. Its effects on apoptosis, glycolysis, and the cell cycle were also investigated. Finally, the impact of SPINK4 overexpression on tumor development was assessed using a xenograft model, while histological and immunohistochemical analyses characterized SPINK4 expression patterns in CRC tissues. SPINK4 expression was downregulated in CRC, correlating with poor patient prognosis. In vitro assays confirmed that overexpression of SPINK4 reduced CRC cell proliferation, invasion, and migration, while its knockdown promoted these processes and caused G1 arrest. SPINK4 also regulated apoptosis by altering caspase activation and Bcl-2 expression. Besides, SPINK4 overexpression altered glycolytic activity, reduced 2-Deoxy-D-glucose (2-DG) absorption, and controlled critical glycolytic enzymes, resulting in alterations in metabolic pathways, whereas SPINK4 knockdown reversed this effect. SPINK4 overexpression significantly reduced tumor volume in vivo, indicating its inhibitory role in carcinogenesis. Moreover, high expression of SPINK4, hexokinase 2 (HK2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) was observed in CRC tissues. As a key inhibitor of glycolytic metabolism in CRC, SPINK4 promises metabolic intervention in CRC therapy due to its impact on tumor growth and cell proliferation.

An NIR-II-emitting type-I photosensitizer for efficient hypoxic tumor phototheranostics.

A small molecule-based NIR-II type-I photosensitizer (IT-IC) with a strong push-pull effect and good planar π-conjugated structure was synthesized. The IT-IC NPs exhibited strong light absorption, outstanding NIR-II fluorescence emission, excellent photothermal conversion and efficient type-I/II ROS generation, showing encouraging therapeutic outcomes for hypoxic tumors.

Discovery of a novel SHP2 allosteric inhibitor using virtual screening, FMO calculation, and molecular dynamic simulation.

CONTEXT: SHP2 is a non-receptor protein tyrosine phosphatase to remove tyrosine phosphorylation. Functionally, SHP2 is an essential bridge to connect numerous oncogenic cell-signaling cascades including RAS-ERK, PI3K-AKT, JAK-STAT, and PD-1/PD-L1 pathways. This study aims to discover novel and potent SHP2 inhibitors using a hierarchical structure-based virtual screening strategy that combines molecular docking and the fragment molecular orbital method (FMO) for calculating binding affinity (referred to as the Dock-FMO protocol). For the SHP2 target, the FMO method prediction has a high correlation between the binding affinity of the protein-ligand interaction and experimental values (R2 = 0.55), demonstrating a significant advantage over the MM/PBSA (R2 = 0.02) and MM/GBSA (R2 = 0.15) methods. Therefore, we employed Dock-FMO virtual screening of ChemDiv database of ∼2,990,000 compounds to identify a novel SHP2 allosteric inhibitor bearing hydroxyimino acetamide scaffold. Experimental validation demonstrated that the new compound (E)-2-(hydroxyimino)-2-phenyl-N-(piperidin-4-ylmethyl)acetamide (7188-0011) effectively inhibited SHP2 in a dose-dependent manner. Molecular dynamics (MD) simulation analysis revealed the binding stability of compound 7188-0011 and the SHP2 protein, along with the key interacting residues in the allosteric binding site. Overall, our work has identified a novel and promising allosteric inhibitor that targets SHP2, providing a new starting point for further optimization to develop more potent inhibitors. METHODS: All the molecular docking studies were employed to identify potential leads with Maestro v10.1. The protein-ligand binding affinities of potential leads were further predicted by FMO calculations at MP2/6-31G* level using GAMESS v2020 system. MD simulations were carried out with AmberTools18 by applying the FF14SB force field. MD trajectories were analyzed using VMD v1.9.3. MM/GB(PB)SA binding free energy analysis was carried out with the mmpbsa.py tool of AmberTools18. The docking and MD simulation results were visualized through PyMOL v2.5.0.

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

ABSTRACT: Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

Distinct brain network organizations between club players and novices under different difficulty levels.

SIGNIFICANT: Chunk memory is one of the essential cognitive functions for high-expertise (HE) player to make efficient decisions. However, it remains unknown how the neural mechanisms of chunk memory processes mediate or alter chess players' performance when facing different opponents. AIM: This study aimed at inspecting the significant brain networks associated with chunk memory, which would vary between club players and novices. APPROACH: Functional networks and topological features of 20 club players (HE) and 20 novice players (LE) were compared at different levels of difficulty by means of functional near-infrared spectroscopy. RESULTS: Behavioral performance indicated that the club player group was unaffected by differences in difficulty. Furthermore, the club player group demonstrated functional connectivity among the dorsolateral prefrontal cortex, the frontopolar cortex, the supramarginal gyrus, and the subcentral gyrus, as well as higher clustering coefficients and lower path lengths in the high-difficulty task. CONCLUSIONS: The club player group illustrated significant frontal-parietal functional connectivity patterns and topological characteristics, suggesting enhanced chunking processes for improved chess performance.

Safety and feasibility of minimally invasive gastrectomy after neoadjuvant immunotherapy for locally advanced gastric cancer: a propensity score-matched analysis in China.

Background: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) for locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare short-term outcomes between MIG after neoadjuvant chemo-immunotherapy (NICT-MIG) and MIG after neoadjuvant chemotherapy alone (NCT-MIG), and determine risk factors for post-operative complications (POCs). Methods: This retrospective study included clinicopathologic data from 193 patients who underwent NCT-MIG or NICT-MIG between January 2020 and February 2023 in the Department of General Surgery, Chinese People's Liberation Army General Hospital First Medical Center (Beijing, China). Propensity score-matched analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables and short-term outcomes were compared between the two groups. Results: The baseline characteristics were comparable between 49 patients in the NICT-MIG group and 86 patients in the NCT-MIG group after propensity score matching. Objective and pathologic complete response rates were significantly higher in the NICT-MIG group than in the NCT-MIG group (P < 0.05). The overall incidence of treat-related adverse events, intraoperative bleeding, operation time, number of retrieved lymph nodes, time to the first flatus, post-operative duration of hospitalization, overall morbidity, and severe morbidity were comparable between the NCT-MIG and NICT-MIG groups (P > 0.05). By multivariate logistic analysis, estimated blood loss of >200 mL (P = 0.010) and prognostic nutritional index (PNI) score of <45 (P = 0.003) were independent risk factors for POCs after MIG following neoadjuvant therapy. Conclusions: Safety and feasibility of NICT were comparable to those of NCT in patients undergoing MIG for LAGC. Patients with an estimated blood loss of >200 mL or a PNI score of <45 should be carefully evaluated for increased POCs risk.

Evaluation of the learning state of online video courses based on functional near infrared spectroscopy.

Studying brain activity during online learning will help to improve research on brain function based on real online learning situations, and will also promote the scientific evaluation of online education. Existing research focuses on enhancing learning effects and evaluating the learning process associated with online learning from an attentional perspective. We aimed to comparatively analyze the differences in prefrontal cortex (PFC) activity during resting, studying, and question-answering states in online learning and to establish a classification model of the learning state that would be useful for the evaluation of online learning. Nineteen university students performed experiments using functional near-infrared spectroscopy (fNIRS) to monitor the prefrontal lobes. The resting time at the start of the experiment was the resting state, watching 13 videos was the learning state, and answering questions after the video was the answering state. Differences in student activity between these three states were analyzed using a general linear model, 1s fNIRS data clips, and features, including averages from the three states, were classified using machine learning classification models such as support vector machines and k-nearest neighbor. The results show that the resting state is more active than learning in the dorsolateral prefrontal cortex, while answering questions is the most active of the three states in the entire PFC, and k-nearest neighbor achieves 98.5% classification accuracy for 1s fNIRS data. The results clarify the differences in PFC activity between resting, learning, and question-answering states in online learning scenarios and support the feasibility of developing an online learning assessment system using fNIRS and machine learning techniques.

Research into the anatomy of the subaxial cervical pedicle for ensuring screw insertion safety.

The study aimed to determine the optimal entry points and trajectories for posterior subaxial cervical pedicle screw (CPS) fixation. Computed tomography (CT) and Mimics software were used to evaluate the subaxial cervical pedicle in 42 cervical spine CT scans. The width of the cervical pedicle was measured and compared at medial angulations of 30°, 35°, 40°, 45°, 50°, 55°, and 60° relative to the midline sagittal plane. Based on an observational examination of the positions of all cervical 3-dimensional models and screws, the proposed entry point for C3-7 CPS was analyzed. Although the variations in C3-6 pedicle width (PW) among 45°, 50°, and 55° were not statistically significant, they were significantly larger than the differences among 30°, 35°, 40°, and 60° angles (P < .05). The differences in C7 PW between the 30°, 35°, 40°, and 45° angles were not statistically different even though the 30°, 35°, 40°, and 45° angles were significantly bigger. (P < .05). The proposed entry point for C3-7 CPS was below the junction of the lateral and lower borders of the superior articular process joint surface. The entry point for C3-7 levels was below the junction of the lateral and lower borders of the superior articular process joint surface. The optimal medial angulation for the posterior C3-6 CPS was 45°-55° and that for the posterior C7 CPS was 30°-45°. The sagittal angle of the posterior C3-7 CPS was parallel to the corresponding upper endplate.

Identification, screening and taste mechanisms analysis of two novel umami pentapeptides derived from the myosin heavy chain of Atlantic cod (Gadus morhua).

Umami peptides are new ingredients for the condiment and seasoning industries, with healthy and nutrition characteristics, some of which were identified from aquatic proteins. This study aims to further explore novel umami peptides from Atlantic cod (Gadus morhua) by combining in silico, nano-HPLC-MS/MS, sensory evaluation, and electronic tongue analysis. Two novel peptides, Leu-Val-Asp-Lys-Leu (LVDKL) and Glu-Ser-Lys-Ile-Leu (ESKIL), from the myosin heavy chain of Atlantic cod (Gadus morhua), were screened and confirmed to have strong umami tastes with the thresholds of 0.427 mM and 0.574 mM, respectively. The molecular docking was adopted to explore the interactions between the umami peptides and the umami taste receptor T1R1/T1R3, which showed that the umami peptides interacted with T1R1/T1R3 mainly by electrostatic interaction, hydrogen bond interaction, and hydrophobic interaction. Furthermore, the physicochemical properties of the peptides were investigated by in silico methods and cell viability experiments. This study will provide a better understanding of the umami taste in Atlantic cod and will promote the development of condiments and seasonings.

Irreversible Transmural Intestinal Necrosis in Acute Mesenteric Ischemia: Retrospective Cohort Study from a High-Volume Hospital.

Background: Owing to the low incidence rate and nonspecific symptoms of acute mesenteric ischemia (AMI), the identification and prediction of irreversible transmural intestinal necrosis (ITIN) and extensive bowel resection (≥100 cm) (EBR) are difficult and critical. This study aimed to investigate the risk factors for ITIN and EBR in patients with AMI. Methods: The clinical data of 254 AMI patients were retrospectively analyzed. Furthermore, the incidence of ITIN and EBR were set as dependent variables, and relevant risk factors were screened using univariate and multivariate logistic regression analyses. The comparisons of surgical characteristics and postoperative recovery outcomes between the EBR and control group were also conducted. Results: The presence of hemorrhagic (odds ratio [OR] = 28.356, P < .001) or other types ascites (OR = 13.051, P = .003), peritonitis (OR = 8.463, P = .005), intestinal diameter >2.35 cm (OR = 5.493, P = .020), and serum creatinine (CREA) >95 µmol/L (OR = 4.866, P = .048) were identified as independent risk factors for ITIN in patients with AMI. In addition, serum C-reactive protein (CRP) >15 mg/L (OR = 38.023, P = .006), and CREA >100 µmol/L (OR = 6.248, P = .035) were proved to be independently associated with EBR for ITIN cases. Compared to the control group, EBR significantly increased the likelihood of requiring enterostomy (P = .001), blood transfusion (P = .002), and transfer to intensive care unit (P = .016), while also prolonging the recovery time for intestinal function (P = .014). Conclusions: The presence of ascites, peritonitis, intestinal diameter >2.35 cm, and serum CREA >95 µmol/L were independently correlated with ITIN for AMI cases, while serum CRP >15 mg/L and CREA >100 µmol/L independently increased the risk of EBR.

Natural Fat Nanoemulsions for Enhanced Optical Coherence Tomography Neuroimaging and Tumor Imaging in the Second Near-Infrared Window.

Optical coherence tomography (OCT) imaging mainly uses backscattered light to visualize the structural and functional information on biological tissues. In particular, OCT angiography can not only map the capillary networks but also capture the blood flow in the tissue microenvironment, making it a good candidate for neuroimaging and tumor imaging in vivo and in real time. To further improve the detection accuracy of cancer or brain disorders, it is essential to develop a natural and nontoxic contrast agent for enhanced OCT imaging in the second near-infrared (NIR-II) window. In this study, a superior biocompatible and highly scattering NIR-II fat nanoemulsion was constructed to improve OCT imaging contrast and depth for monitoring the vascular network changes of the cerebral cortex or tumor. In vivo experimental results demonstrated that a natural fat nanoemulsion can serve as an excellent probe for enhanced OCT neuroimaging and tumor imaging.