KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fontisubflavum oceani gen. nov., sp. nov., isolated from the deep-sea cold seep water of South China Sea.

In this study, we report a Gram-stain-negative, rod-shaped, atrichous and aerobic bacterial strain named CSW1921T, which was isolated from the deep-sea water of a cold seep in South China Sea. Growth of strain CSW1921T occurred at 10.0-35.0 °C (optimum, 30 °C), pH 5.0-10.0 (optimum, pH 8.0-9.0) and with 0-9.0 % (w/v) NaCl (optimum, 1.0-2.0 %). Phylogenetic tree analysis based on 16S rRNA gene sequence or the genomic sequence indicated that strain CSW1921T belonged to the family Rhodobacteraceae and was closely related to Rhodophyticola porphyridii MA-7-27T (97.5 % sequence similarity). Genomic analysis indicated that strain CSW1921T contains a circular chromosome of 3 592 879 bp with G+C content of 60.5 mol%. The predominant respiratory quinone of CSW1921T was ubiquinone-10. The polar lipids of CSW1921T contained phosphatidylglycerol, three unidentified aminolipids, two unidentified phospholipids and two unidentified lipids. The major fatty acids of strain CSW1921T contained C16 : 0, C18 : 1 ω7c 11-methyl and summed feature 8 (C18 : 1 ω7c). The average nucleotide identity, DNA-DNA hybridization and average amino acid identity values between strain CSW1921T and members of its related species were 68.02-69.08 %, 12.7-12.9 % and 46.87-48.08 %, respectively, which were lower than the recommended threshold values for bacterial species or genus delineation. Phylogenetic, physiological, biochemical and morphological analyses suggested that strain CSW1921T represents a novel genus and a novel species of the family Rhodobacteraceae, and the name Fontisubflavum oceani gen. nov., sp. nov. is proposed with the type strain CSW1921T (=MCCC 1K08371T=KCTC 92834T).

Pore Environmental Modification by Amino Groups in Robust Microporous MOFs for SF6 Capturing and SF6/N2 Separation.

Capturing and separating the greenhouse gas SF6 from nitrogen N2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH2). This resulted in an enhanced adsorption of SF6 and separation of the SF6/N2 mixture in the MOF. The introduction of amino (-NH2) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF6 within the confined pores. Water-stable YTU-29-NH2 showed a significantly higher SF6 uptake (95.5 cm3/g) than YTU-29 (77.4 cm3/g). The results of the breakthrough experiments show that YTU-29-NH2 has a significantly improved separation performance for SF6/N2 mixtures, with a high SF6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH2 demonstrates great potential for SF6 capturing and SF6/N2 separation.

Description of Fuscovulum ytuae sp. nov, a facultative autotroph isolated from the intertidalite of Yangma island, China.

In this study, we reported a Gram-stain-negative, ovoid to rod-shaped, atrichous, and facultative anaerobe bacteria strain named YMD61T, which was isolated from the intertidal sediment of Yangma island, China. Growth of strain YMD61T occurred at 10.0-45.0 °C (optimum, 30.0 °C), pH 7.0-10.0 (optimum, 8.0) and with 0-3.0% (w/v) NaCl (optimum, 2.0%). Phylogenetic tree analysis based on 16 S rRNA gene or genomic sequence indicated that strain YMD61T belonged to the genus Fuscovulum and was closely related to Fuscovulum blasticum ATCC 33,485T (96.6% sequence similarity). Genomic analysis indicated that strain YMD61T contains a circular chromosome of 3,895,730 bp with DNA G + C content of 63.3%. The genomic functional analysis indicated that strain YMD61T is a novel sulfur-metabolizing bacteria, which is capable of fixing carbon through an autotrophic pathway by integrating the processes of photosynthesis and sulfur oxidation. The predominant respiratory quinone of YMD61T was ubiquinone-10 (Q-10). The polar lipids of YMD61T contained phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, five unidentified lipids, unidentified aminolipid and unidentified aminophospholipid. The major fatty acids of strain YMD61T contained C18:1ω7c 11-methyl and summed feature 8 (C18:1 ω 7c or/and C18:1 ω 6c). Phylogenetic, physiological, biochemical and morphological analyses suggested that strain YMD61T represents a novel species of the genus Fuscovulum, and the name Fuscovulum ytuae sp. nov. is proposed. The type strain is YMD61T (= MCCC 1K08483T = KCTC 43,537T).

Pseudo Elevation of TSH and ACTH Caused by Heterophilic Antibodies: a Case Report and Literature Review.

BACKGROUND: TSH and ACTH are crucial hormones for diagnosing thyroid and adrenal diseases, and incorrect test reports can cause significant harm to patients. METHODS: The TSH and ACTH levels on the testing system of our laboratory were measured using "sandwich" assays. The patient had heterophilic antibodies in their body, causing a false increase in TSH and ACTH levels. RESULTS: TSH on the Abbott platform was 59.7 µIU/mL and on the Roche platform it was 4.33 µIU/mL. After pretreatment with HBR it was 3.95 µIU/mL; ACTH on the SIEMENS platform was 263.5 pg/mL, on the Abbott platform it was 47.6 pg/mL. After pretreatment with HBR it was 36.5 pg/mL. CONCLUSIONS: The patient's serum contains heterophilic antibodies, which interfere with the TSH and ACTH tested by this method.

A Pseudo Elevation of CEA Caused by Epidemic Hemorrhagic Fever.

BACKGROUND: Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment. METHODS: This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body. RESULTS: The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 µmol/L, epidemic hemorrhagic fever IgM antibody was positive. CONCLUSIONS: When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease.

[Effects of urogenital mycoplasma and chlamydial infections on male fertility].

Objective： This study aimed to assess the impact of urogenital ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) infections on semen quality in men.Methods： In this study, 1022 males were enrolled at the Department of Reproductive Medicine, Rizhao People's Hospital, Shandong Province from October 2014 to January 2023. The participants included 393 in the infertility group, 139 in the recurrent miscarriage group, and 490 in the control group. Based on age, 852 cases were < 36 years old, and 170 cases were ≥ 36 years old. All patients underwent routine semen analysis and tests for Uu, Mh, and Ct, with results statistically analyzed for their impact on semen quality and compared among different age groups. Results: Among the 1022 patients, 344 (33.6%) were Uu-positive, 49 (4.7%) were Mh-positive, and 31 (3.0%) were Ct positive. The sperm concentration, total sperm count, forward sperm motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate of Uu Mh and/or Ct-positive patients were significantly lower than those of the negative group, and the overall difference between the two groups was statistically significant (P<0.05). The positive rate of Uu infection was 41.7% in the infertility group, 30.2% in the recurrent miscarriage group and 28.2% in the control group, and the overall positive rate of the three groups was statistically significant(P<0.05). The positive rate of Mh infection was 6.9% in the infertility group, 8.6% in the recurrent miscarriage group and 2.0% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positive rate of Ct infection was 6.1% in the infertility group, 2.9% in the recurrent miscarriage group and 0.6% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positivity rate of Uu infection was 35.8% at the age of <36 years and 22.9% at the age ≥ 36 years, and there was a statistically significant difference in the positivity rate between the two groups (P<0.05). Conclusion: The prevalence of Uu infection in the male urogenital tract is significantly higher than that of Mh and Ct, which is the main pathogen of urogenital tract infection in men. Uu, Mh and Ct infections have adverse effects on sperm concentration, total sperm count, sperm forward motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate, which will lead to a decrease in semen quality and affect male fertility. Genital tract infections are closely related to age, and the prevalence of Uu infection is higher in the younger age group.

Rbm24 modulates neuronal RNA splicing to restrict cognitive dysfunction.

Synaptic dysfunction is associated with early neurodegenerative changes and cognitive deficits. Neuronal cell-specific alternative splicing (AS) programs exclusively encode unique neuron- and synapse-specific proteins. However, it remains unclear whether splicing disturbances in neurons influence the pathogenesis of cognitive impairment. Here, we observed that RNA-binding motif protein 24 (RBM24) expression was decreased in Alzheimer's disease (AD) patients. Using conditional RBM24 knockout mice, we demonstrated that deletion of RBM24 in the brain resulted in learning and memory impairment. Electrophysiological recordings from hippocampal slices from mice lacking RBM24 revealed multiple defects in excitatory synaptic function and plasticity. Furthermore, RNA sequencing and splicing analysis showed that RBM24 regulates a network of genes related to cognitive function. Deletion of RBM24 disrupted the AS of synapse-associated genes, including GluR2 and Prrt1, the major disease genes involved in cognitive impairment and memory loss, leading to cognitive dysfunction. Together, our results suggest that the regulation of mRNA splicing by RBM24 is a key process involved in maintaining normal synaptic function and provide novel mechanistic insights into the pathogenesis of AD.

[Spatial and temporal distribution characteristics of extreme wind and its effect on wind erosion in Northeast China]. / ä¸œåŒ—åœ°åŒºæžç«¯å¤§é£Žæ—¶ç©ºåˆ†å¸ƒç‰¹å¾åŠå ¶å¯¹é£Žèš€é‡çš„å½±å“.

Under the background of climate change, extreme wind events occur frequently in Northeast China, and the soil erosion caused by these extreme wind events has attracted progressively more attention from scholars. We used the methods of linear analysis, Sen+Mann-Kendal trend analysis, and Kriging interpolation to analyze the spatial and temporal characteristics of extreme wind in Northeast China from 2005 to 2020, and used the RWEQ wind erosion estimation model to calculate the annual soil wind erosion of typical wind erosion sites and wind erosion under extreme wind conditions. The results showed that the extreme wind frequency in Northeast China presented a significant upward trend from 2005 to 2020, with an increase of 2.9 times·a-1. The annual average extreme wind frequency in Northeast China ranged from 1 to 49 times·a-1, and the high frequency areas were distributed in the northwest of Xilin Gol, the west of the Hulunbuir Plateau, and the northeast of Changbai Mountain. The average contribution rate of extreme wind to soil wind erosion in four typical sites (Xilinhot, New Barhu Right Banner, Nenjiang, and Tongyu) was 31%.

Misdiagnosed Meckel's diverticulum with internal hernia mimicking appendicitis: A case report.

BACKGROUND: Meckel's diverticulum is a common congenital anomaly of the gastrointestinal tract, with a higher incidence rate in children under 7 years old. The condition is characteristically asymptomatic but may become a clinical concern when complications such as intestinal obstruction, bleeding, perforation, or diverticulitis precipitate acute abdominal presentations. CASE SUMMARY: This report describes the case of a middle-aged man initially suspected of having acute appendicitis, which rapidly progressed to acute peritonitis with concomitant intestinal obstruction observed during preoperative assessment. Surgical exploration confirmed the diagnosis of Meckel's diverticulum-induced internal hernia, accompanied by intestinal obstruction and necrosis. In addition, the hernial ring base exhibited entrapment resembling a surgical knot. CONCLUSION: Meckel's diverticulum is a rare cause of small bowel obstruction in adults, and it should be considered in a differential diagnosis.

Triterpenoids with α-glucosidase inhibitory and cytotoxic activities from the fruits of Schisandra chinensis.

An intensive phytochemical investigation into the fruits of Schisandra chinensis afforded 28 triterpenoids incorporating diverse backbones with methyl-migration, ring-expansion and ring-opening features. Among them, ten compounds (1-10) including three likely extracting artefacts (8-10) were described for the first time. Their structures were fully characterized by comprehensive spectroscopic analyses, with the absolute configurations established via electronic circular dichroism and Mosher's NMR techniques. Preliminary biological evaluations revealed that nine isolates showed inhibitory activity against the hyperglycemic target α-glycosidase and 12 compounds exerted cytotoxicity toward three female tumor cell lines (Hela (cervical), MDA-MB231 and MCF-7 (breast)). Compound 6 exhibited the most promising potency on all the three tested cancer cells, and further assessment demonstrated that it could induce significant cell apoptosis and cycle arrest, as well as suppress cell migration, by regulating relevant proteins in MDA-MB231 cells.

[ABO*A2.08 Subtype Allele Identification and Protein Structure Analysis in Newborns].

OBJECTIVE: To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism. METHODS: ABO blood group identification was performed on proband and her family members by routine serological methods. ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer (PCR-SSP), and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed. The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis, 3D molecular modeling and protein stability prediction. RESULTS: The proband's serological test results showed subtype Ax, and ABO genotyping confirmed that the proband's genotype was ABO*A207/08. Gene sequencing of the proband's father confirmed the characteristic variation of c.539G>C in the 7th exon of ABO gene, leading to the replacement of polypeptide chain p.Arg180Pro (R180P). 3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation, and protein stability prediction showed that the mutation had a great influence on the protein structure stability. CONCLUSION: The mutation of the 7th exon c.539G>C of ABO gene leads to the substitution of polypeptide chain amino acid, which affects the structural stability of GTA protein and leads to the change of enzyme activity, resulting in the A2.08 phenotype. The mutated gene can be stably inherited.

A numerical study on the siphonic effect of enhanced external counterpulsation at lower extremities with a coupled 0D-1D closed-loop personalized hemodynamics model.

Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.

Computational Interpersonal Communication Model for Screening Autistic Toddlers: A Case Study of Response-to-Name.

Interpersonal communication facilitates symptom measures of autistic sociability to enhance clinical decision-making in identifying children with autism spectrum disorder (ASD). Traditional methods are carried out by clinical practitioners with assessment scales, which are subjective to quantify. Recent studies employ engineering technologies to analyze children's behaviors with quantitative indicators, but these methods only generate specific rule-driven indicators that are not adaptable to diverse interaction scenarios. To tackle this issue, we propose a Computational Interpersonal Communication Model (CICM) based on psychological theory to represent dyadic interpersonal communication as a stochastic process, providing a scenario-independent theoretical framework for evaluating autistic sociability. We apply CICM to the response-to-name (RTN) with 48 subjects, including 30 toddlers with ASD and 18 typically developing (TD), and design a joint state transition matrix as quantitative indicators. Paired with machine learning, our proposed CICM-driven indicators achieve consistencies of 98.44% and 83.33% with RTN expert ratings and ASD diagnosis, respectively. Beyond outstanding screening results, we also reveal the interpretability between CICM-driven indicators and expert ratings based on statistical analysis.

Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction.

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.

Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS: A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS: Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION: We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Bibliometric analysis of Mongolian medicine and medicinal materials in China since 2000.

Aim of the study: To analyze the progress in Mongolian medicine and medicinal materials and to highlight its development process, emerging trends, and hotspots. Materials and methods: Papers on Mongolian medicine and medicinal materials from January 2000 to May 2022 were retrieved from the China National Knowledge Infrastructure (CNKI) database. Using the collaboration network analysis of CiteSpace V and VOSviewer software, the cooperation among individuals and institutions in the field of scientific research was analyzed. The functions of frequency analysis, cluster analysis, and burst analysis were employed to conduct bibliometric analysis on research hotspots and trends in the field of Mongolian medicine research. Furthermore, the data visualization function was utilized to clearly display data trends and changes. Results: A total of 8362 papers on Mongolian medicine medicinal materials from CNKI were identified and analyzed.The research on Mongolian medicine has gone through three stages: the initial stage, the exploratory stage, and the developmental stage. The top two institutions in the number of papers are Inner Mongolia Medical University and Inner Mongolia University for Nationalities. Bagenna from Inner Mongolia Medical University is the author with the most papers. "clinical efficacy", "clinical research", and "quality standards" were the most frequently used keywords. Research in the field of Mongolian medicine has focused on several diseases, including skeletal system disorders, cardiovascular diseases, and digestive system disorders. Conclusion: Since 2000, there have been growing attention and efforts made in the field of Mongolian medicine and medicinal materials. The research in the field of Mongolian medicine had undergone three stages, namely the initial stage, the exploratory stage, and the developmental stage. The focus shifted from basic research such as the analysis of medicinal ingredients in Mongolian herbs to the application-oriented directions of traditional treatment techniques and advantageous diseases in Mongolian medicine. To make breakthroughs in this field, further research is needed to improve the persuasiveness and authority of Mongolian medicine and medicinal materials in terms of mechanism, standardization, and safety, to promote the development of Mongolian medicine and medicinal materials.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.