RING finger protein 122-like (RNF122L) negatively regulates antiviral immune response by targeting STING in common carp (Cyprinus carpio L.).

Stimulator of interferon genes (STING), as an imperative adaptor protein in innate immune, responds to nucleic acid from invading pathogens to build antiviral responses in host cells. Aberrant activation of STING may trigger tissue damage and autoimmune diseases. Given the decisive role in initiating innate immune response, the activity of STING is intricately governed by several posttranslational modifications, including phosphorylation and ubiquitination. Here, we cloned and characterized a novel RNF122 homolog from common carp (named CcRNF122L). Expression analysis disclosed that the expression of CcRNF122L is up-regulated under spring viremia of carp virus (SVCV) stimulation in vivo and in vitro. Overexpression of CcRNF122L hampers SVCV- or poly(I:C)-mediated the expression of IFN-1 and ISGs in a dose-dependent way. Mechanistically, CcRNF122L interacts with STING and promotes the polyubiquitylation of STING. This polyubiquitylation event inhibits the aggregation of STING and the subsequent recruitment of TBK1 and IRF3 to the signaling complex. Additionally, the deletion of the TM domain abolishes the negative regulatory function of CcRNF122L. Collectively, our discoveries unveil a mechanism that governs the STING function and the precise adjustment of the innate immune response in teleost.

Low expression of ACOT13 predicts poor prognosis and immunotherapy outcome in ovarian cancer.

OBJECTIVE: Acyl-CoA thioesterase 13 (ACOT13) is involved in lipid biosynthesis, gene transcription, and signal transduction. We explored the potential of ACOT13 to predict ovarian cancer (OC) prognosis and patient immunotherapy responses. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus databases were used to extract raw data. To investigate the potential of ACOT13 as a prognostic and immunotherapeutic marker for OC, bioinformatic analyses were performed using the TIMER website, LinkedOmics database, and R software. We also explored the effects on the invasive ability of OC cells in vitro using a ACOT13 knockdown. RESULTS: The expression of ACOT13 in OC was high and associated with a better prognosis. The expression of ACOT13 was also linked to immune cell invasion immunity-related gene expression. Additionally, immunotherapy was more effective in patients with high ACOT13 expression levels. Multiple critical signaling pathways were found to be involved in the role of ACOT13 in energy metabolism and cell mobility based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. OC cells invaded and migrated significantly more when ACOT13 was knocked down. CONCLUSION: High ACOT13 expression in OC is associated to a better OC outcome.

Comparative genomics analysis of pheophorbide a oxygenase (PAO) genes in eight pyrus genomes and their regulatory role in multiple stress responses in Chinese pear (Pyrus bretschneideri).

Pyrus (pear) is among the most nutritious fruits and contains fibers that have great health benefits to humans. It is mostly cultivated in temperate regions globally and is highly subjected to biotic and abiotic stresses which affect its yield. Pheophorbide a oxygenase (PAO) is an essential component of the chlorophyll degradation system and contributes to the senescence of leaves. It is responsible for opening the pheophorbide a porphyrin macrocycle and forming the main fluorescent chlorophyll catabolite However, this gene family and its members have not been explored in Pyrus genomes. Here we report a pangenome-wide investigation has been conducted on eight Pyrus genomes: Cuiguan, Shanxi Duli, Zhongai 1, Nijisseiki, Yunhong No.1, d'Anjou, Bartlett v2.0, and Dangshansuli v.1.1. The phylogenetic history, their gene structure, conservation patterns of motifs, their distribution on chromosomes, and gene duplication are studied in detail which shows the intraspecific structural conservation as well as evolutionary patterns of Pyrus PAOs. Cis-elements, protein-protein interactions (PPI), and the Gene Ontology (GO) enrichment analyses show their potential biological functions. Furthermore, their expression in various tissues, fruit hardening conditions, and drought stress conditions is also studied. Based on phylogenetics, the identified PAOs were divided into four groups. The expansion of this gene family in Pyrus is caused by both tandem and segmental duplication. Moreover, positive and negative selection pressure equally directed the gene's duplication process. The Pyrus PAO genes were enriched in hormones-related, light, development, and stress-related elements. RNA-seq data analysis showed that PAOs have varied levels of expression under diseased and abiotic stress conditions. The 3D structures of PAOs are also predicted to get more insights into functional conservation. Our research can be used further to get a deeper knowledge of the PAO gene family in Pyrus and to guide future research on improving the genetic composition of Pyrus to enhance stress tolerance.

Advances in contezolid: novel oxazolidinone antibacterial in Gram-positive treatment.

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.

Circulating Tumor Cell Phenotype Detection and Epithelial-Mesenchymal Transition Tracking Based on Dual Biomarker Co-Recognition in an Integrated PDMS Chip.

Circulating tumor cells (CTCs) are widely considered as a reliable and promising class of markers in the field of liquid biopsy. As CTCs undergo epithelial-mesenchymal transition (EMT), phenotype detection of heterogeneous CTCs based on EMT markers is of great significance. In this report, an integrated analytical strategy that can simultaneously capture and differentially detect epithelial- and mesenchymal-expressed CTCs in bloods of non-small cell lung cancer (NSCLS) patients is proposed. First, a commercial biomimetic polycarbonate (PCTE) microfiltration membrane is employed as the capture interface for heterogenous CTCs. Meanwhile, differential detection of the captured CTCs is realized by preparing two distinct CdTe quantum dots (QDs) with red and green emissions, attached with EpCAM and Vimentin aptamers, respectively. For combined analysis, a polydimethylsiloxane (PDMS) chip with simple structure is designed, which integrates the membrane capture and QDs-based phenotype detection of CTCs. This chip not only implements the analysis of the number of CTCs down to 2 cells mL-1, but enables EMT process tracking according to the specific signals of the two QDs. Finally, this method is successfully applied to inspect the correlations of numbers or proportions of heterogenous CTCs in 94 NSCLS patients with disease stage and whether there is distant metastasis.

Epigenetic regulation of high light-induced anthocyanin biosynthesis by histone demethylase IBM1 in Arabidopsis.

In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.

Investigation of high-dose radiotherapy's effect on brain structure aggravated cognitive impairment and deteriorated patient psychological status in brain tumor treatment.

This study aims to investigate the potential impact of high-dose radiotherapy (RT) on brain structure, cognitive impairment, and the psychological status of patients undergoing brain tumor treatment. We recruited and grouped 144 RT-treated patients with brain tumors into the Low dose group (N = 72) and the High dose group (N = 72) according to the RT dose applied. Patient data were collected by using the HADS and QLQ-BN20 system for subsequent analysis and comparison. Our analysis showed no significant correlation between the RT doses and the clinicopathological characteristics. We found that a high dose of RT could aggravate cognitive impairment and deteriorate patient role functioning, indicated by a higher MMSE and worsened role functioning in the High dose group. However, the depression status, social functioning, and global health status were comparable between the High dose group and the Low dose group at Month 0 and Month 1, while being worsened in the High dose group at Month 3, indicating the potential long-term deterioration of depression status in brain tumor patients induced by high-dose RT. By comparing patient data at Month 0, Month 1, Month 3, Month 6, and Month 9 after RT, we found that during RT treatment, RT at a high dose could aggravate cognitive impairment in the short term and lead to worsened patient role functioning, and even deteriorate the overall psychological health status of patients in the long term.

Rapunzel syndrome in children: a retrospective review of ten cases combined with literature review in a tertiary referral center.

PURPOSE: Rapunzel syndrome is an uncommon condition in children, and its clinical features remain unclear. This study presents the largest single-center series of pediatric cases to date, with the objective of documenting the clinical characteristics and treatment approaches for children with Rapunzel syndrome. METHODS: A retrospective study was conducted in children with Rapunzel syndrome from 2019 to 2023. We recorded age, gender, symptoms, locations of bezoar, complications, and treatment options. RESULTS: Ten patients with Rapunzel syndrome were included. The median age was 9.1 years, with all of whom were female. The most common clinical symptoms were upper abdominal mass (90%), abdominal pain (80%), and nausea and vomiting (50%). Complications occurred in six cases (60%), including small bowel obstruction (20%), severe gastric dilatation (10%), intestinal perforation (10%), choledochodilation (10%), acute pancreatitis with cholecystitis (10%). Preoperative ultrasonography suggested low-echoic foreign bodies continuing to the jejunum or ileocecal region in five cases (50%). Preoperative gastroscopy attempted in four cases (40%) to remove the foreign bodies, all of which failed. All patients underwent surgical treatment, with nine cases undergoing gastric incision foreign body removal, and one case undergoing gastric incision foreign body removal combined with intestinal perforation repair. All patients recovered well. No recurrence was observed during follow-up. CONCLUSION: The accuracy of ultrasound diagnosis in identifying Rapunzel syndrome is high; however, it may lead to misdiagnosis if not complemented with the patient's medical history. Endoscopic presents a heightened treatment risk and a reduced success rate. The condition commonly presents with severe complications, thus making laparotomy a safe and effective option for intervention.

Identification and fine mapping of Brmmd1 gene controlling recessive genic male sterility in Brassica rapa L.

Recessive genic male sterility (RGMS) provides an effective approach for the commercial exploitation of heterosis, especially in Brassica crops. Although some artificial RGMS mutants have been reported in B. rapa, no causal genes derived from these natural mutants have been identified so far. In this study, a spontaneous RGMS mutant Bcajh97-01A derived from the 'Aijiaohuang' line traced back to the 1980 s was identified. Genetic analysis revealed that the RGMS trait was controlled by a single locus in the Bcajh97-01A/B system. Bulk segregant analysis (BSA) in combination with linkage analysis was employed to delimit the causal gene to an approximate 129 kb interval on chromosome A02. The integrated information of transcriptional levels and the predicted genes in the target region indicated that the Brmmd1 (BraA02g017420) encoding a PHD-containing nuclear protein was the most likely candidate gene. A 374 bp miniature inverted-repeat transposable element (MITE) was inserted into the first exon to prematurely stop the Brmmd1 gene translation, thus blocking the normal expression of this gene at the tetrad stage in the Bcajh97-01A. Additionally, a co-segregating structure variation (SV) marker was developed to rapidly screen the RGMS progenies from Bcajh97-01A/B system. Our findings reveal that BraA02g017420 is the causal gene responsible for the RGMS trait. This study lays a foundation for marker-assisted selection and further molecular mechanism exploration of pollen development in B. rapa.

Targeting leucine-rich PPR motif-containing protein/LRPPRC by 5,7,4'-trimethoxyflavone suppresses esophageal squamous cell carcinoma progression.

JAK2/STAT3/MYC axis is dysregulated in nearly 70 % of human cancers, but targeting this pathway therapeutically remains a big challenge in cancer therapy. In this study, genes associated with JAK2, STAT3, and MYC were analyzed, and potential target genes were selected. Leucine-rich PPR motif-containing protein (LRPPRC) whose function and regulation are not fully understood, emerged as one of top 3 genes in terms of RNA epigenetic modification. Here, we demonstrate LRPPRC may be an independent prognostic indicator besides JAK2, STAT3, and MYC. Mechanistically, LRPPRC impairs N6-methyladenosine (m6A) modification of JAK2, STAT3, and MYC to facilitate nuclear mRNA export and expression. Meanwhile, excess LRPPRC act as a scaffold protein binding to JAK2 and STAT3 to enhance stability of JAK2-STAT3 complex, thereby facilitating JAK2/STAT3/MYC axis activation to promote esophageal squamous cell carcinoma (ESCC) progression. Furthermore, 5,7,4'-trimethoxyflavone was verified to bind to LRPPRC, STAT3, and CDK1, dissociating LRPPRC-JAK2-STAT3 and JAK2-STAT3-CDK1 interaction, leading to impaired tumorigenesis in 4-Nitroquinoline N-oxide induced ESCC mouse models and suppressed tumor growth in ESCC patient derived xenograft mouse models. In summary, this study suggests regulation of m6A modification by LRPPRC, and identifies a novel triplex target compound, suggesting that targeting LRPPRC-mediated JAK2/STAT3/MYC axis may overcome JAK2/STAT3/MYC dependent tumor therapeutic dilemma.

Switchable divergent synthesis of chiral indole derivatives via catalytic asymmetric dearomatization of 2,3-disubstituted indoles.

A strategy allowing the switchable divergent synthesis of chiral indole derivatives was established via chiral phosphoric acid-catalyzed asymmetric dearomatization of 2,3-disubstituted indoles using naphthoquinone monoimines as electrophiles. The products were switched between chiral indolenines and fused indolines according to the post-processing conditions. Both two types of products were obtained in good to high yields with generally excellent enantioselectivities. NaBH4 was found to work as a promoter as well as a reductant in the cyclization process leading to fused indolines.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Clinical presentation of severe COVID­19 with heart failure: A single­center retrospective study.

The coronavirus disease-19 (COVID-19) pandemic has led to a global transformation in public health interventions. The present study aimed to evaluate the clinical features as well as the outcomes of severe heart failure (HF) among patients with severe COVID-19. A single-center observational study was carried out at The 904th Hospital of Joint Logistic Support Force (Wuxi, China) from November 2022 to April 2023, and a total of 210 patients diagnosed with severe HF were included. Among these patients, 128 patients had COVID-19 whereas the remaining patients were not diagnosed with COVID-19. The analysis entailed investigated pre-existing medical records, that is, admission and discharge, laboratory values, neuroimaging, length of hospitalization, mortality and costs incurred by patients throughout the COVID-19 pandemic from the records. All the 210 incorporated patients accomplished the follow-up and it was established that there was no significant differences in baseline characteristics between HF combined with COVID-19 and HF without COVID-19 were affirmed (P>0.05). HF coupled with COVID-19 infection demonstrated an increased risk of 30-day mortality (28.91 vs. 14.63%; P=0.017), extended length of hospital stays (22.54±6.73 vs. 19.35±5.69; P<0.001) and higher expenses for hospitalization (P<0.001). Complications related to hospitalization, including pneumonia (76.56 vs. 35.37%; P=1.0x10-4), respiratory failure (47.66 vs. 24.39%; P=0.001), pulmonary embolism (8.59 vs. 2.44%; P=0.031), deep vein thrombosis (30.47 vs. 14.63%; P=0.009), 7 days delirium (60.16 vs. 45.12%; P=0.033), multiple organ dysfunction syndrome (32.81 vs. 18.29%; P=0.021) and neurological deficits (30.47% vs. 17.07%, P=0.029) increased significantly. In conclusion, HF combined with COVID-19, treatment and prognosis are getting worse. Enhancing preparedness for future COVID-19 and other similar pandemics necessitates the comprehension of this to refine care provided to patients with HF (registration no. THH-IPR-20221101 on 01 November 2022).

L-fucose and fucoidan alleviate high-salt diet-promoted acute inflammation.

Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation in vitro. In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.

Metagenomic next-generation sequencing for the diagnosis of neurobrucellosis.

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.

Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.

Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.

Clinical features of intussusception in children secondary to small bowel tumours: a retrospective study of 31 cases.

BACKGROUND: Summarizing the clinical features of children with intussusception secondary to small bowel tumours and enhancing awareness of the disease. METHODS: Retrospective summary of children with intussusception admitted to our emergency department from January 2016 to January 2022, who underwent surgery and were diagnosed with small bowel tumours. Summarize the types of tumours, clinical presentation, treatment, and prognosis. RESULTS: Thirty-one patients were included in our study, 24 males and 7 females, with an age of onset ranging from 1 m to 11y 5 m. Post-operative pathology revealed 4 types of small intestinal tumour, 17 lymphomas, 10 adenomas, 4 inflammatory myofibroblastomas and 1 lipoma. The majority of tumours in the small bowel occur in the ileum (83.9%, 26/31). Abdominal pain, vomiting and bloody stools were the most common clinical signs. Operative findings indicated that the small bowel (54.8%, 17/31) and ileocolic gut were the main sites of intussusception. Two types of procedure were applied: segmental bowel resection (28 cases) and wedge resection of mass in bowel wall (3 cases). All patients recovered well postoperatively, with no surgical complications observed. However, the primary diseases leading to intussusception showed slight differences in long-term prognosis due to variations in tumor types. CONCLUSIONS: Lymphoma is the most common cause of intussusception in pediatric patients with small bowel tumours, followed by adenoma. Small bowel tumours in children tend to occur in the ileum. Therefore, the treatment of SBT patients not only requires surgeons to address symptoms through surgery and obtain tissue samples but also relies heavily on the expertise of pathologists for accurate diagnosis. This has a significant impact on the overall prognosis of these patients.

Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.