A 3'-pre-tRNA-derived small RNA tRF-1-Ser regulated by 25(OH)D promotes proliferation and stemness by inhibiting the function of MBNL1 in breast cancer.

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.

Comprehensive molecular characterization of long-term glioblastoma survivors.

Fewer than 5% glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4+ T cells (P = 0.031) and CD4+ Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8% of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.

Developing and validating prediction models for severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO) in China: a prospective observational study.

BACKGROUND: There is a lack of individualised prediction models for patients hospitalised with chronic obstructive pulmonary disease (COPD) for clinical practice. We developed and validated prediction models of severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO). METHODS: Data were obtained from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry study (NCT02657525) in China. Cause-specific hazard models were used to estimate coefficients. C-statistic was used to evaluate the discrimination. Slope and intercept were used to evaluate the calibration and used for model adjustment. Models were validated internally by 10-fold cross-validation and externally using data from different regions. Risk-stratified scoring scales and nomograms were provided. The discrimination ability of the SERCO model was compared with the exacerbation history in the previous year. RESULTS: Two sets with 2196 and 1869 patients from different geographical regions were used for model development and external validation. The 12-month severe exacerbations cumulative incidence rates were 11.55% (95% CI 10.06% to 13.16%) in development cohorts and 12.30% (95% CI 10.67% to 14.05%) in validation cohorts. The COPD-specific readmission incidence rates were 11.31% (95% CI 9.83% to 12.91%) and 12.26% (95% CI 10.63% to 14.02%), respectively. Demographic characteristics, medical history, comorbidities, drug usage, Global Initiative for Chronic Obstructive Lung Disease stage and interactions were included as predictors. C-indexes for severe exacerbations were 77.3 (95% CI 70.7 to 83.9), 76.5 (95% CI 72.6 to 80.4) and 74.7 (95% CI 71.2 to 78.2) at 1, 6 and 12 months. The corresponding values for readmissions were 77.1 (95% CI 70.1 to 84.0), 76.3 (95% CI 72.3 to 80.4) and 74.5 (95% CI 71.0 to 78.0). The SERCO model was consistently discriminative and accurate with C-indexes in the derivation and internal validation groups. In external validation, the C-indexes were relatively lower at 60-70 levels. The SERCO model discriminated outcomes better than prior severe exacerbation history. The slope and intercept after adjustment showed close agreement between predicted and observed risks. However, in external validation, the models may overestimate the risk in higher-risk groups. The model-driven risk groups showed significant disparities in prognosis. CONCLUSION: The SERCO model provides individual predictions for severe exacerbation and COPD-specific readmission risk, which enables identifying high-risk patients and implementing personalised preventive intervention for patients with COPD.

Machine learning models to predict submucosal invasion in early gastric cancer based on endoscopy features and standardized color metrics.

Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists' experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l'Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.

The DEP1 Mutation Improves Stem Lodging Resistance and Biomass Saccharification by Affecting Cell Wall Biosynthesis in Rice.

BACKGROUND: Plant cell walls have evolved precise plasticity in response to environmental stimuli. The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits. However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown. RESULTS: In this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification. The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls. The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mechanical properties relative to the wild-type, leading to a substantial improvement in lodging resistance. Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI). Additionally, the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition. Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymatic saccharification of biomass after the alkali pretreatment. Furthermore, the comparative transcriptome analysis revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis. CONCLUSIONS: Our findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

Spinel Nanostructures for the Hydrogenation of CO2 to Methanol and Hydrocarbon Chemicals.

Composite oxides have been widely applied in the hydrogenation of CO/CO2 to methanol or as the component of bifunctional oxide-zeolite for the synthesis of hydrocarbon chemicals. However, it is still challenging to disentangle the stepwise formation mechanism of CH3OH at working conditions and selectively convert CO2 to hydrocarbon chemicals with narrow distribution. Here, we investigate the reaction network of the hydrogenation of CO2 to methanol over a series of spinel oxides (AB2O4), among which the Zn-based nanostructures offer superior performance in methanol synthesis. Through a series of (quasi) in situ spectroscopic characterizations, we evidence that the dissociation of H2 tends to follow a heterolytic pathway and that hydrogenation ability can be regulated by the combination of Zn with Ga or Al. The coordinatively unsaturated metal sites over ZnAl2Ox and ZnGa2Ox originating from oxygen vacancies (OVs) are evidenced to be responsible for the dissociative adsorption and activation of CO2. The evolution of the reaction intermediates, including both carbonaceous and hydrogen species at high temperatures and pressures over the spinel oxides, has been experimentally elaborated at the atomic level. With the integration of a series of zeolites or zeotypes, high selectivities of hydrocarbon chemicals with narrow distributions can be directly produced from CO2 and H2, offering a promising route for CO2 utilization.

The inflammatory immunity and gut microbiota are associated with fear response differences in laying hens.

The fear response is a crucial adaptive mechanism for coping with environmental changes, and the individuals have different levels of fearfulness. The purpose of this study was to determine the status of the immune response and gut health in hens with different fear responses. A total of 80 healthy 75-wk-old native Lindian chickens were individually housed in conventional cages and categorized into high (TH) and low (TL) levels of fearfulness using the tonic immobility (TI) test. The immunological status and intestinal health of the laying hens were assessed, and the intestinal microbial community was sequenced using 16S rRNA testing. The results showed that the immune-related genes of interleukin (IL)-1ß, IL-4, IL-6, and IgG were significantly upregulated in the spleen of TH hens compared with hens in the TL group (P < 0.01). The inflammatory immune-related genes Toll-like receptor (TLR)2, TLR4, nuclear factor (NF)-κB, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, IL-10, and IgG were significantly increased in the intestinal tract, whereas IL-4, IgA, and the intestinal barrier gene claudin-4 were significantly decreased in TH hens (P < 0.05). In addition, serum concentrations of IL-1ß, IL-6, IL-10, interferon (IFN)-α and IgG were significantly higher in TH hens (P < 0.01). A high fear response also led to changes in gut microbial diversity, with a higher Simpson's index and lower ß-diversity similarity than hens with a low-fear response (P < 0.05). The TH group showed an increase in 8 genera, including Bacillaceae and Coprococcus, whereas the genus Anaerorhabdus decreased (P < 0.05). The gut microbiota has also been associated with gut barrier genes, and inflammatory cytokines. Bartonella stimulates IL-1ß and IgG secretion, whereas Lactobacillus inhibits IL-6 secretion, and Coprococcus and Subdoligranulum are associated with the maintenance of intestinal barrier function. The results of this study suggest that laying hens with high fear response levels have a more sensitive immune response and a more enriched gut microbiota, which may have positive effects on adapting to a complex environment.

Comparison of the analgesic effects of oxycodone vs. sufentanil on postoperative pain after laparoscopic gallbladder-preserving cholecystolithotomy: a prospective randomized controlled trial.

Background: We aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy, as well as changes in serum levels of inflammatory factors (TNF-α, IL-6, and IL-10) in the perioperative period. Methods: Sixty patients who underwent laparoscopic gallbladder-preserving cholecystolithotomy were evenly divided into oxycodone (O) and sufentanil (S) groups. In groups O and S, oxycodone (0.3 mg/kg) and sufentanil (0.3 ug/kg) were administered, respectively, followed by propofol (2 mg/kg) and rocuronium (0.6 mg/kg). In both groups, the intraoperative electroencephalography double-frequency index was used to guide the use of sedative and analgesic drugs, assessing the follow-up analgesic effect (VAS), degree of sedation (Ramsey), and postoperative complications at seven different time points (0, 0.5, 2, 4, 6, 8, and 24 h postoperatively). Results: Compared with the S group, patients in the O group exhibited lower VAS scores within 24 h postoperatively (P < 0.001), but there was no statistical difference between wound and shoulder pain scores (P > 0.05). Regarding postoperative awakening and extubation duration, O group patients experienced shorter times and better remedial analgesia (P < 0.05). In terms of the degree of sedation, the Ramsay score decreased at 0 h postoperatively compared with the S group (P < 0.001). Conclusion: Compared with sufentanil, oxycodone anesthesia induced better postoperative analgesia and less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy. Clinical Trial Registration: This study has been approved by the Ethics Committee of Peking University Shougang Hospital, with ethical approval (No. IRBK-2020-009), and has completed registration in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) (ChiCTR2000031230).

Angular-resolved Rabi oscillations of orthorhombic spins in a Co(II) molecular qubit.

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

Conditional survival nomogram for patients with colon mucinous adenocarcinoma to predict prognosis: a dynamic survival analysis.

The aim was to assess conditional survival for colon mucinous adenocarcinoma (MAC) patients, and to construct nomograms to predict conditional survival probability. Survival analysis was done using conditional survival, which was defined as the probability of surviving additional y years for patients who have survived for x years. The mathematical definition was express as: CS (y|x) = S (x + y)/S (x). Cox regression analyses were used to identify prognostic factors. A nomogram is constructed to predict conditional disease-free survival (DFS) and overall survival (OS) probability according to years that already survive. A total of 179 colon MAC patients were included. The 5-year DFS was 67% after surgery, and the 5-year survival probability of patients, who already survived 1, 2, 3, and 4 years were 75%, 87%, 95%, and 98%, respectively. The 5-year OS was 73% after surgery and increased to 76%, 82%, 88%, and 92% at 1, 2, 3, and 4 years, respectively. Subgroup analyses demonstrated the superiority of conditional survival was more pronounced in advanced stages than in stage I. And pT stage, pN stage, and lymphovascular invasion were significantly associated with DFS and OS. Conditional survival nomograms were constructed to predict the 5-year conditional DFS and OS probability given survival for 1, 2, 3, 4 years after surgery. Conditional survival can provide dynamic survival probability according to years that already survive, especially for patients with advanced stages. Taking into account the years already survived accounted for, novel nomograms contributed to effectively predicting conditional survival.

Improvement of functional dyspepsia with Suaeda salsa (L.) Pall via regulating brain-gut peptide and gut microbiota structure.

PURPOSE: The traditional Chinese herbal medicine Suaeda salsa (L.) Pall (S. salsa) with a digesting food effect was taken as the research object, and its chemical composition and action mechanism were explored. METHODS: The chemical constituents of S. salsa were isolated and purified by column chromatography, and their structures were characterized by nuclear magnetic resonance. The food accumulation model in mice was established, and the changes of the aqueous extract of S. salsa in gastric emptying and intestinal propulsion rate, colonic tissue lesions, serum brain-gut peptide hormone, colonic tissue protein expression, and gut microbiota structure were compared. RESULTS: Ten compounds were isolated from S. salsa named as naringenin (1), hesperetin (2), baicalein (3), luteolin (4), isorhamnetin (5), taxifolin (6), isorhamnetin-3-O-ß-D-glucoside (7), luteolin-3'-D-glucuronide (8), luteolin-7-O-ß-D-glucuronide (9), and quercetin-3-O-ß-D-glucuronide (10), respectively. The aqueous extract of S. salsa can improve the pathological changes of the mice colon and intestinal peristalsis by increasing the rate of gastric emptying and intestinal propulsion. By adjusting the levels of 5-HT, CCK, NT, SS, VIP, GT-17, CHE, MTL, and ghrelin, it can upregulate the levels of c-kit, SCF, and GHRL protein, and restore the imbalanced structure of gut microbiota, further achieve the purpose of treating the syndrome of indigestion. The effect is better with the increase of dose. CONCLUSION: S. salsa has a certain therapeutic effect on mice with the syndrome of indigestion. From the perspective of "brain-gut-gut microbiota", the mechanism of digestion and accumulation of S. salsa was discussed for the first time, which provided an experimental basis for further exploring the material basis of S. salsa.

Smooth-Guided Implicit Data Augmentation for Domain Generalization.

The training process of a domain generalization (DG) model involves utilizing one or more interrelated source domains to attain optimal performance on an unseen target domain. Existing DG methods often use auxiliary networks or require high computational costs to improve the model's generalization ability by incorporating a diverse set of source domains. In contrast, this work proposes a method called Smooth-Guided Implicit Data Augmentation (SGIDA) that operates in the feature space to capture the diversity of source domains. To amplify the model's generalization capacity, a distance metric learning (DML) loss function is incorporated. Additionally, rather than depending on deep features, the suggested approach employs logits produced from cross entropy (CE) losses with infinite augmentations. A theoretical analysis shows that logits are effective in estimating distances defined on original features, and the proposed approach is thoroughly analyzed to provide a better understanding of why logits are beneficial for DG. Moreover, to increase the diversity of the source domain, a sampling-based method called smooth is introduced to obtain semantic directions from interclass relations. The effectiveness of the proposed approach is demonstrated through extensive experiments on widely used DG, object detection, and remote sensing datasets, where it achieves significant improvements over existing state-of-the-art methods across various backbone networks.

A Large-Scale Online Survey on Clinical Severity and Associated Risk Factors for SARS-CoV-2 Omicron Infection - China, April-May 2023.

What is already known about this topic?: Individuals who initially contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack significant mixed immunity. Therefore, it is crucial to monitor the clinical characteristics and associated factors of these individuals in order to inform policy-making. What is added by this report?: The common symptoms reported were fever, cough, and sore throat. Reinfections and receiving four vaccination doses within a 6-month period were found to be associated with a shorter duration of virus shedding, decreased hospitalization rate, and reduced risk of pneumonia. Individuals aged 60 years and older, as well as those with underlying medical conditions, had a higher risk of developing pneumonia. What are the implication for public health practices?: Online surveys conducted through social media platforms have the potential to complement disease surveillance and data collection efforts. In terms of vaccination prioritization, it is recommended to prioritize older individuals and those with underlying diseases.

Unraveling Stoichiometry Effect in Nickel-Tungsten Alloys for Efficient Hydrogen Oxidation Catalysis in Alkaline Electrolytes.

Anion-exchange membrane fuel cells provide the possibility to use platinum group metal-free catalysts, but the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics and its source is still debated. Here, over nickel-tungsten (Ni-W) alloy catalysts, we show that the Ni:W ratio greatly governs the HOR performance in alkaline electrolyte. Experimental and theoretical studies unravel that alloying with W can tune the unpaired electrons in Ni, tailoring the potential of zero charge and the catalytic surface to favor hydroxyl adsorption (OHad). The OHad species coordinately interact with potassium (K+) ions, which break the K+ solvation sheath to leave free water molecules, yielding an improved connectivity of hydrogen-bond networks. Consequently, the optimal Ni17W3 alloy exhibits alkaline HOR activity superior to the state-of-the-art platinum on carbon (Pt/C) catalyst and operates steadily with negligible decay after 10,000 cycles. Our findings offer new understandings of alloyed HOR catalysts and will guide rational design of next-generation catalysts for fuel cells.

Strand-Specific RNA Sequencing Reveals Gene Expression Patterns in F1 Chick Breast Muscle and Liver after Hatching.

Heterosis refers to the phenomenon where hybrids exhibit superior performance compared to the parental phenotypes and has been widely utilized in crossbreeding programs for animals and crops, yet the molecular mechanisms underlying this phenomenon remain enigmatic. A better understanding of the gene expression patterns in post-hatch chickens is very important for exploring the genetic basis underlying economically important traits in the crossbreeding of chickens. In this study, breast muscle and liver tissues (n = 36) from full-sib F1 birds and their parental pure lines were selected to identify gene expression patterns and differentially expressed genes (DEGs) at 28 days of age by strand-specific RNA sequencing (ssRNA-seq). This study indicates that additivity is the predominant gene expression pattern in the F1 chicken post-hatch breast muscle (80.6% genes with additivity) and liver (94.2% genes with additivity). In breast muscle, Gene Ontology (GO) enrichment analysis revealed that a total of 11 biological process (BP) terms closely associated with growth and development were annotated in the identified DEG sets and non-additive gene sets, including STAT5A, TGFB2, FGF1, IGF2, DMA, FGF16, FGF12, STAC3, GSK3A, and GRB2. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation presented that a total of six growth- and development-related pathways were identified, involving key genes such as SLC27A4, GLUL, TGFB2, COX17, and GSK3A, including the PPAR signaling pathway, TGF-beta signaling pathway, and mTOR signaling pathway. Our results may provide a theoretical basis for crossbreeding in domestic animals.

The impact of US-China tensions on US science: Evidence from the NIH investigations.

Amid the discourse on foreign influence investigations in research, this study examines the impact of NIH-initiated investigations starting in 2018 on U.S. scientists' productivity, focusing on those collaborating with Chinese peers. Using publication data from 2010 to 2021, we analyze over 113,000 scientists and find that investigations coincide with reduced productivity for those with China collaborations compared to those with other international collaborators, especially when accounting for publication impact. The decline is particularly pronounced in fields that received greater preinvestigation NIH funding and engaged more in U.S.-China collaborations. Indications of scientist migration and broader scientific progress implications also emerge. We also offer insights into the underlying mechanisms via qualitative interviews.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Successful treatment of gastric cancer 10 years after heart transplantation: A case report.

BACKGROUND: While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION: A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION: This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.