The Journal retracts the article “Inhibition of AKT2 Enhances Sensitivity to Gemcitabine via Regulating PUMA and NF-κB Signaling Pathway in Human Pancreatic Ductal Adenocarcinoma” [...]

Background and Objective: Transcription factor Engrailed-1 (EN1) has been implicated as an oncogene in various solid tumors; however, its role in papillary thyroid carcinoma (PTC) is unknown. In the present study, the authors investigate the EN1 expression in PTC clinical specimens and its correlation with clinical outcomes, and then explore its function in PTC progression using in vitro and in vivo models.Methods: A retrospective cohort of 376 paired PTC was collected with informed consent. Immunohistochemistry for EN1 protein expression was evaluated. Clinic pathological data were recorded. EN1-specific shRNAs (or siRNAs) and overexpression plasmids were used. Using En-1 knockdown and overexpression, cell invasion, migration, proliferation, and apoptosis in vitro were detected using Transwell and wound healing assays, MTT, colony formation assay, and flow cytometry assay, respectively. Xenograft tumor models (subcutaneous) and tail-vein injection metastasis models (lung colonization) were established in mice.Results: EN1 is significantly overexpressed in PTC tissues; high EN1 expression is correlated with lymphovascular invasion (p < 0.05), lymph node metastasis (p < 0.05), TNM stage (p < 0.05), and recurrence (p < 0.05). Functionally enhanced EN1 expression promotes PTC cell invasion and migration, and promotes cell proliferation in vitro. Conversely, EN1 knockdown potently inhibited this invasive phenotype, induced significant apoptosis, and inhibited cell proliferation. EN1 silencing reduced tumor growth and lung metastatic potential in murine models in vivo. EN1 overexpression enhanced these malignant phenotypes in vivo.Conclusions: EN1 may be a novel driver of PTC aggressiveness and metastasis, suggesting its potential utility as a prognostic biomarker and therapeutic target.

Background and aims Targeting key enzymes in hepatic de novo lipogenesis (DNL) presents a promising strategy for treating hypercholesterolemia. However, the precise regulatory mechanisms governing hepatic DNL remain incompletely understood. Cytosolic citrate plays a crucial role in DNL, with aconitase 1 (ACO1), a key enzyme in citrate metabolism, potentially influencing lipid metabolism. The aim of this study was to clarify the role of hepatic ACO1 in regulating both hepatic and systemic lipid homeostasis. Methods ACO1 expression and activity were assessed in liver tissues from multiple hypercholesterolemic animal models. Using liver-specific genetic manipulation, we examined the effects of hepatic ACO1 knockout and overexpression on hypercholesterolemia and atherosclerosis. Targeted metabolomics and stable isotope-based flux analysis were used to profile hepatic substrate utilization patterns. Results Hepatic ACO1 expression was significantly reduced in both hypercholesterolemic patients and animal models. Hepatocyte-specific ACO1 deletion exacerbated dyslipidemia, while ACO1 overexpression improved hypercholesterolemia, hepatic steatosis, and atherosclerosis in mouse models. Mechanistically, ACO1 overexpression redirected cytosolic citrate metabolism toward α-ketoglutarate, thereby limiting acetyl-CoA availability for DNL and suppressing fatty acid and cholesterol synthesis. These lipid-lowering effects were dependent on ACO1 enzymatic activity, as catalytically inactive ACO1 mutants failed to replicate the observed benefits. Conclusion Our findings identify hepatic ACO1 as a critical regulator of lipid metabolism homeostasis. Promoting ACO1-mediated citrate redirection effectively mitigates hypercholesterolemia and atherosclerosis by suppressing hepatic DNL, highlighting ACO1 as a potential target for lipid-lowering therapies.

High thermoelectric performance is generally achieved by synergistically optimizing two or even three of the contradictorily coupled thermoelectric parameters. Here we demonstrate magneto-thermoelectric correlation as a strategy to achieve simultaneous gain in an enhanced Seebeck coefficient and reduced thermal conductivity in topological materials. We report a large magneto-Seebeck effect and high magneto-thermoelectric figure of merit of 1.7 ± 0.2 at 180 K and 0.7 T in a single-crystalline Bi88Sb12 topological insulator. This result fills a gap of a high performance below 300 K and is promising for low-temperature thermoelectric applications. The large magneto-Seebeck response is attributed to the ultrahigh mobility and the Dirac band dispersion. The application of a low magnetic field to achieve a high thermoelectric performance can be extended to topological materials with similar features that are rapidly emerging because it synergistically optimizes the thermoelectric parameters. Applying a magnetic field to the topological material Bi88Sb12 enhances the Seebeck coefficient, resulting in a high thermoelectric figure of merit zT of 1.7 at 180 K and 0.7 T.

The kagome ferrimagnet family RMn6Sn6 (R = Gd - Er) features Chern-gapped Dirac points in the band structure, theoretically allowing a large anomalous Hall effect. However, the experimentally observed anomalous Hall effect in RMn6Sn6 is only comparable to those found in conventional ferromagnets. Here, we report a significant enhancement of anomalous Hall effect in the kagome ferrimagnet TbMn6Sn6 induced by local disorder through Mg substitution on Tb. By electrical transport and anomalous Nernst effect measurements, combined with first-principles calculations, we demonstrate that the Mg substitution modulates the band structure of TbMn6Sn6, leading to an increase in intrinsic anomalous Hall conductivity. Additionally, the modulated band structure enhances the longitudinal conductivity, further boosting the extrinsic anomalous Hall conductivity dominated by skew scattering. Consequently, the total anomalous Hall conductivity reaches 950 Q-1cm-1, entering the regime of topological magnets. Both of the large intrinsic and extrinsic anomalous Hall conductivity can be attributed to the nontrivial band structure near the Fermi level.

Weyl semimetals have attracted considerable research interest over the past decade, with a number of intriguing transport phenomena reported. Magnetic Weyl semimetals, which break time reversal symmetry, have been predicted and recently discovered. Co3Sn2S2 is a magnetic Weyl semimetal that exhibit a giant anomalous Hall effect (AHE) when the magnetic moments are aligned along the c axis. In this paper, we report the evolution of the AHE with an external magnetic field applied in the ab plane and current along the c axis, namely, the out-of-plane AHE of Co3Sn2S2. Density functional theory calculations predict a finite out-of-plane AHE when the spins are fully aligned in the ab plane. The evolution of the magnetic structure modifies the nodal line distribution and the Berry curvature, resulting in a weaker AHE with an amplitude of 200Scm−1 at the saturation field. To ensure the alignment of the magnetic field in the ab plane, a two-round scanning process was performed experimentally. After this, the out-of-plane AHE was measured at multiple temperatures. The observed AHE signals with applied fields of 1 and 2 T were in good agreement with theoretical predictions. These results suggest that engineering the anomalous Hall effect may be possible by designing the symmetry relation of the local Berry curvature. Published by the American Physical Society 2025

BACKGROUND Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery. AIM To explore the effect of the operative position during bariatric surgery on PONV. METHODS Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors’ hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t -test were used to study the influence of operative position on PONV. RESULTS There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) (P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group (P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766). CONCLUSION Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery.

Background Laparoscopic sleeve gastrectomy (LSG) is currently the most commonly performed bariatric surgery due to its effective weight loss and low complication rates. However, some patients experience weight regain or insufficient weight loss due to residual gastric dilation, the factors of which are unclear. This study uses 3D CT reconstruction to measure changes in residual gastric volume after LSG and investigates factors contributing to gastric dilation and its impact on weight loss. Method This retrospective study involved 50 LSG patients. Preoperative clinical and laboratory data were collected. Residual gastric volume was measured using 3D CT reconstruction at 1 and 3 months post-surgery. The study assessed total sleeve volume (TSV), tube volume (TV), and antral volume (AV). Resected gastric volume and staple line length were measured during surgery. Weight metrics and laboratory indices were recorded at 1, 3, 6, and 12 months post-surgery. The Three-Factor Eating Questionnaire-R21 (TFEQ-R21), the Eating Behavior and Belief Scale Questionnaire (EBBS-Q), and the Gastroesophageal Reflux Disease Questionnaire (GERD-Q) were used to assess patients' postoperative dietary behavior, treatment adherence, and reflux condition, respectively. Correlations between weight metrics, residual gastric dilation, and the aforementioned factors were analyzed. Results The 50 patients had a mean preoperative BMI of 42.27 ± 7.19 kg/m² and an average total weight loss (%TWL) of 34 ± 7% one year post-LSG. One month post-LSG, mean TV, AV, and TSV were 45.93 ± 16.75 mL, 115.85 ± 44.92 mL, and 161.77 ± 55.37 mL, respectively. %TWL at one year significantly correlated with residual gastric dilation (p < 0.05). Three months post-surgery, the degree of residual gastric dilation was 13.50 ± 17.35%. Initial residual gastric volume, preoperative diabetes, and postoperative reflux were associated with dilation. Conclusion Residual gastric dilation post-LSG significantly affects weight loss efficacy. Factors including initial residual residual gastric volume, preoperative diabetes, and postoperative reflux are associated with residual gastric dilation.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Background: The aim of this study was to evaluate the effects of the enhanced recovery after surgery (ERAS) program versus conventional perioperative care on the short-term postoperative outcomes among elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. Methods: Elderly patients with gastric cancer (age >= 65 y) who are undergoing laparoscopic total gastrectomy were randomized to ERAS or conventional perioperative care groups. Short-term postoperative outcomes, including postoperative hospital stay, mortality, complications, readmission rate, and reoperation rate were compared between the two groups. In addition, blood samples were taken preoperatively (baseline) and on postoperative days 1, 3, and 5. Systemic human leukocyte antigen (HLA)-DR expression on monocytes and C-reactive protein (CRP) were analyzed. Results: Of the 171 eligible patients, 85 patients were assigned to receive ERAS program treatment (ERAS group) and 86 patients to receive conventional care (conventional group). The patients' characteristics were comparable. Postoperative hospital stay was shorter in the ERAS group than in the conventional group (11 [7-11] versus 13 [8-20] d, P 0.001). Hospital mortality, overall morbidity, morbidity Clavien-Dindo (C-D) grade II, readmission rate, and reoperation rate did not show significant differences between the two groups. However, morbidity >= C-D grade IIIa was lower in the ERAS group than that in the conventional group (8.2% versus 18.6%, P = 0.047). The ERAS program shortened the number of days to postoperative first flatus, first defecation, semifluid diet, and soft bland diet. Moreover, the ERAS program increased the HLA-DR expression on monocytes and decreased the CRP levels on postoperative days 1, 3, and 5. Conclusions: The ERAS program was feasible and effective for elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. The benefits of ERAS were associated with improvement of impaired immune function and suppression of inflammatory reaction. (c) 2020 Elsevier Inc. All rights reserved.

The kagome metals AV_3Sb_5 (A=K,Rb,Cs) present an ideal sandbox to study the interrelation between multiple coexisting correlated phases such as charge order and superconductivity. So far, no consensus on the microscopic nature of these states has been reached as the proposals struggle to explain all their exotic physical properties. Among these, field-switchable electric magneto-chiral anisotropy (eMChA) in CsV_3Sb_5 provides intriguing evidence for a rewindable electronic chirality, yet the other family members have not been likewise investigated. Here, we present a comparative study of magneto-chiral transport between CsV_3Sb_5 and KV_3Sb_5. Despite their similar electronic structure, KV_3Sb_5 displays negligible eMChA, if any, and with no field switchability. This is in stark contrast to the non-saturating eMChA in CsV_3Sb_5 even in high fields up to 35 T. In light of their similar band structures, the stark difference in eMChA suggests its origin in the correlated states. Clearly, the V kagome nets alone are not sufficient to describe the physics and the interactions with their environment are crucial in determining the nature of their low-temperature state.

Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 levels are increased in patients with thoracic aortic dissection (TAD). TAD shares several risk factors with abdominal aortic aneurysm (AAA). However, the role of ANGPTL8 in AAA pathogenesis has never been investigated. Here, we investigated the effect of ANGPTL8 knockout on AAA in ApoE(-/-) mice. ApoE(-/-) ANGPTL8(-/-) mice were generated by crossing ANGPTL8(-/-) and ApoE(-/-) mice. AAA was induced in ApoE(-/-) using perfusion of angiotensin II (AngII). ANGPTL8 was significantly up-regulated in AAA tissues of human and experimental mice. Knockout of ANGPTL8 significantly reduced AngII-induced AAA formation, elastin breaks, aortic inflammatory cytokines, matrix metalloproteinase expression, and smooth muscle cell apoptosis in ApoE(-/-) mice. Similarly, ANGPTL8 sh-RNA significantly reduced AngII-induced AAA formation in ApoE(-/-) mice. ANGPTL8 deficiency inhibited AAA formation, and ANGPTL8 may therefore be a potential therapeutic target for AAA.

Purpose:Kinetochore scaffold 1 (KNL1), a crucial protein during cell mitosis participating in cell division, was widely expressed in multiple kinds of cancers. However, the expression profile, the effect on cell biological function, tumor immune microenvironment, and predictive value of clinical prognosis in pan-cancer of KNL1 still require a comprehensive inquiry.Methods:The mRNA and protein expression profile of KNL1 was validated in pan-cancer using different databases. Six algorithms were used to explore the correlation between KNL1 and immune infiltration and the relationship between KNL1 and tumor mutation burden (TMB), microsatellite instability (MSI), and TIDE score were calculated. The diagnostic and clinical prognostic predictive ability of KNL1 was assessed. Differentially expressed genes (DEGs) of KNL1 were screened out and function enrichment analyses were performed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and bladder urothelial carcinoma (BLCA). Finally, 8 cases of pancreatic adenocarcinoma tissues and paired adjacent tissues were collected for immunohistochemical (IHC) staining and the histological score (H-score) was calculated. Real-time PCR was performed in gastric cancer and bladder cancer cell lines.Results:KNL1 was abnormally upregulated in more than half of cancers across different databases. IHC and real-time PCR verified the up-regulated expression in cancer tissues in PAAD, gastric cancer, and BLCA. The satisfactory diagnostic value of KNL1 was indicated in 30 cancers and high KNL1 expression was associated with poorer overall survival (OS) in 12 cancers. The prognostic role of KNL1 as a predictive biomarker of PAAD was clarified. KNL1 played an active part in the cell cycle and cell proliferation. Moreover, KNL1 was likely to mold the Th2-dominant suppressive tumor immune microenvironment and was associated with TMB, MSI, and immune checkpoint-related genes in pan-cancer.Conclusion:Our study elucidated the anomalous expression of KNL1 and revealed that KNL1 was a promising prognostic biomarker in pan-cancer.

Recently, the giant intrinsic anomalous Hall effect (AHE) has been observed in the materials with kagome lattice. In this study, we systematically investigate the influence of high pressure on the AHE in the ferromagnet LiMn6Sn6 with clean Mn kagome lattice. Our in-situ high-pressure Raman spectroscopy indicates that the crystal structure of LiMn6Sn6 maintains a hexagonal phase under high pressures up to 8.51 GPa. The anomalous Hall conductivity (AHC) {\sigma}xyA remains around 150 {\Omega}-1 cm-1, dominated by the intrinsic mechanism. Combined with theoretical calculations, our results indicate that the stable AHE under pressure in LiMn6Sn6 originates from the robust electronic and magnetic structure.

This publication has been retracted by the Editor due to the identification of falsified figure images and manuscript content that raise concerns regarding the credibility of the study and the manuscript. Reference: Vemurafenib Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang. The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib. Med Sci Monit, 2018; 24: 3002-3010. DOI: 10.12659/MSM.910084.

BIOMEDICAL SCIENCE IN BRIEF Br J Biomed Sci, 11 January 2022 https://doi.org/10.3389/bjbs.2021.10268

The objective of this study was to compare the efficacy of exclusive enteral nutrition (EEN) and corticosteroids on the gut microbiome in Crohn’s disease. Methods. Data were collected for 16 patients newly diagnosed with CD as the test group and 10 healthy volunteers as the control group. The 16 patients were randomly divided into the EEN group and the corticosteroids group. For subsequent analysis, 6 patients in the EEN group with follow-up were enrolled to compare the 0-month, 1-month, and 3-month outcomes. We analyzed and compared gut microbiota between different groups in 3 stages. To evaluate the clinical outcome of treatment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (HB), albumin (ALB), and Crohn’s disease activity (CDAI) were recorded. Results. There are significant differences in microbiota between patients with CD and healthy people, and there are intuitive differences in the main components of the microbiota. 16 patients were included in stage 2, in which both corticosteroids and EEN can induce CD remission well. However, corticosteroids have a greater impact on inflammatory indicators, while EEN has a more obvious effect on nutritional indicators. Principal component analysis suggests that there are different compositional changes in the gut microbiome after corticosteroids and EEN treatment. After 3 months of dynamic observation, we found that EEN can effectively maintain CD remission, reduce inflammatory indicators, and improve nutritional indicators. Conclusions. Both EEN and corticosteroids can increase the diversity of the microbiome in inducing CD remission, while they have different effects on the proportion of microbiome species. This trial is registered with NCT02056418.

Transition metal chalcogenides such as CoS2 have been reported as competitive catalysts for oxygen evolution reaction. It has been well confirmed that surface modification is inevitable in such a process, with the formation of different re-constructed oxide layers. However, which oxide species should be responsible for the optimized catalytic efficiencies and the detailed interface structure between the modified layer and precatalyst remain controversial. Here, a topological CoS2 single crystal with a well-defined exposed surface is used as a model catalyst, which makes the direct investigation of the interface structure possible. Cross-sectional transmission electron microscopy of the sample reveals the formation of a 2 nm thickness Co3O4 layer that grows epitaxially on the CoS2 surface. Thick CoO pieces are also observed and are loosely attached to the bulk crystal. The compact Co3O4 interface structure can result in the fast electron transfer from adsorbed O species to the bulk crystal compared with CoO pieces as evidenced by the electrochemical impedance measurements. This leads to the competitive apparent and intrinsic reactivity of the crystal despite the low surface geometric area. These findings are helpful for the understanding of catalytic origins of transition metal chalcogenides and the designing of high-performance catalysts with interface-phase engineering.