The relationship and clinical significance of lactylation modification in digestive system tumors.

Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents a comprehensive review of lactylation in digestive system tumors, underscoring its critical involvement in tumor development and progression. By focusing on metabolic reprogramming, modulation of the tumor microenvironment, and the molecular mechanisms regulating tumor progression, the potential of targeting lactylation as a therapeutic strategy is highlighted. The research reveals that lactylation participates in gene expression regulation and cell signaling by affecting the post-translational states of histones and non-histone proteins, thereby influencing metabolic pathways and immune evasion mechanisms in tumor cells. Furthermore, this study assesses the feasibility of lactylation as a therapeutic target, providing insights for clinical treatment of gastrointestinal cancers. Future research should concentrate on elucidating the mechanisms of lactylation, developing efficient lactylation inhibitors, and validating their therapeutic efficacy in clinical trials, which could transform current cancer treatment and immunotherapy approaches. In summary, this review emphasizes the crucial role of lactylation in tumorigenesis and progression through a detailed analysis of its molecular mechanisms and clinical significance.

Bibliometric analysis reveals the research hotspots and trends of nasopharyngeal carcinoma immunotherapy.

Immunotherapy is a promising strategy for nasopharyngeal carcinoma (NPC), a common and aggressive malignancy with poor prognosis. However, the literature lacks a comprehensive and objective overview of the current research status and trends of immunotherapy-related fields in NPC. We performed a bibliometric analysis of 513 original articles and reviews in English on immunotherapy for NPC from the Web of Science Core Collection database, using CiteSpace and Bibliometrix software tools. We visualized the development trend of publications, the distribution of countries/regions, the co-occurrence of keywords, the collaboration and citation of authors, the citation of journals, the evolution of topics, and the thematic map. We found that the publication volume increased sharply after 2017, with China as the main contributor and leader, the US as an important partner, and the Netherlands as a potential innovator. The research focused on immune checkpoint inhibitors and cell therapy, which were also the hotspots of clinical trials. Tumor microenvironment, immune infiltration, multicenter studies, and novel immunotherapy were the frontier topics and the key challenges for future research. CD137l-DC, lymphoma, and chimeric antigen receptor were emerging topics with good prospects. Our study provides a valuable insight into the research status and trends of immunotherapy for NPC, which may guide future research directions and clinical applications.

A Deep Learning-Based Method for Preventing Data Leakage in Electric Power Industrial Internet of Things Business Data Interactions.

In the development of the Power Industry Internet of Things, the security of data interaction has always been an important challenge. In the power-based blockchain Industrial Internet of Things, node data interaction involves a large amount of sensitive data. In the current anti-leakage strategy for power business data interaction, regular expressions are used to identify sensitive data for matching. This approach is only suitable for simple structured data. For the processing of unstructured data, there is a lack of practical matching strategies. Therefore, this paper proposes a deep learning-based anti-leakage method for power business data interaction, aiming to ensure the security of power business data interaction between the State Grid business platform and third-party platforms. This method combines named entity recognition technologies and comprehensively uses regular expressions and the DeBERTa (Decoding-enhanced BERT with disentangled attention)-BiLSTM (Bidirectional Long Short-Term Memory)-CRF (Conditional Random Field) model. This method is based on the DeBERTa (Decoding-enhanced BERT with disentangled attention) model for pre-training feature extraction. It extracts sequence context semantic features through the BiLSTM, and finally obtains the global optimal through the CRF layer tag sequence. Sensitive data matching is performed on interactive structured and unstructured data to identify privacy-sensitive information in the power business. The experimental results show that the F1 score of the proposed method in this paper for identifying sensitive data entities using the CLUENER 2020 dataset reaches 81.26%, which can effectively prevent the risk of power business data leakage and provide innovative solutions for the power industry to ensure data security.

Nardosinone relieves metabolic-associated fatty liver disease and promotes energy metabolism through targeting CYP2D6.

BACKGROUND: Nardosinone, a major extract of Rhizoma nardostachyos, plays a vital role in sedation, neural stem cell proliferation, and protection of the heart muscle. However, the huge potential of nardosinone in regulating lipid metabolism and gut microbiota has not been reported, and its potential mechanism has not been studied. PURPOSE: To explore the regulation of nardosinone on liver lipid metabolism and gut microbiota. METHODS: In this study, the role of nardosinone in lipid metabolism was investigated in vitro and in vivo by adding it to mouse feed and HepG2 cell culture medium. And 16S rRNA gene sequencing was used to explore its regulatory effect on gut microbiota. RESULTS: Results showed that nardosinone could improve HFD-induced liver injury and abnormal lipid metabolism by promoting mitochondrial energy metabolism in hepatocytes, alleviating oxidative stress damage, and regulating the composition of the gut microbiota. Mechanistically, combined with network pharmacology and reverse docking analysis, it was predicted that CYP2D6 was the target of nardosinone, and the binding was verified by cellular thermal shift assay (CETSA). CONCLUSIONS: This study highlights a novel mechanism function of nardosinone in regulating lipid metabolism and gut microbiota. It also predicts and validates CYP2D6 as a previously unknown regulatory target, which provides new possibilities for the application of nardosinone and the treatment of metabolic-associated fatty liver disease.

Correlation Between Lifestyle Patterns and Cognitive Function Among Community-Dwelling Older Chinese Adults in the Pre-Dementia Stages: A Latent Class Analysis.

Lifestyle activity engagement is a modifiable factor for cognitive decline. We aimed to identify lifestyle patterns (LPs) among community-dwelling older adults in the pre-dementia stages and to explore the links between LPs, cognitive function, and individual characteristics. 702 older Chinese adults were recruited. Three LPs were identified by latent class analysis: active aging lifestyle pattern (AALP), leisure lifestyle pattern (LLP), and work-centered lifestyle pattern (WLP). AALP refers to participation in various activities that are meaningful to individuals and benefit their well-being. LLP is the pattern of activities aimed at recreation. WLP refers to the LP where individuals are most likely to engage in work-related activities. However, only AALP is protected against mild cognitive impairment (MCI). Multinomial logistic regression models revealed the differences in individual characteristics among participants with different LPs, indicating the importance of tailored intervention strategies. As a protective factor against MCI, AALP should be highlighted in community-based care.

Study protocol for a prediction model for mild cognitive impairment in older adults with diabetes mellitus and construction of a nurse-led screening system: a prospective observational study.

INTRODUCTION: With an increasing number of older adults in China, the number of people with cognitive impairment is also increasing. To decrease the risk of dementia, it is necessary to timely detect mild cognitive impairment (MCI), which is the preliminary stage of dementia. The prevalence of MCI is relatively high among older adults with diabetes mellitus (DM); however, no effective screening strategy has been designed for this population. This study will construct a nurse-led screening system to detect MCI in community-dwelling older adults with DM in a timely manner. METHODS AND ANALYSIS: A total of 642 participants with DM will be recruited (n=449 for development, n=193 for validation). The participants will be divided into MCI and none-MCI groups. The candidate predictors will include demographic variables, lifestyle factors, history of diseases, physical examinations, laboratory tests and neuropsychological tests. Univariate analysis, least absolute shrinkage and selection operator regression screening, and multivariate logistic regression analysis will be conducted to identify the outcome indicators. Based on the multivariate logistic regression equation, we will develop a traditional model as a comparison criterion for the machine learning models. The Hosmer-Lemeshow goodness-of-fit test and calibration curve will be used to evaluate the calibration. Sensitivity, specificity, area under the curves and clinical decision curve analysis will be performed for all models. We will report the sensitivity, specificity, area under the curve and decision curve analysis of the validation dataset. A prediction model with better performance will be adopted to form the nurse-led screening system. ETHICS AND DISSEMINATION: This prospective study has received institutional approval of the Medical Ethics Committee of Qidong Hospital of TCM (QDSZYY-LL-20220621). Study results will be disseminated through conference presentations, Chinese Clinical Trial Registry and publication. TRIAL REGISTRATION NUMBER: ChiCTR2200062855.

Cross-cultural adaptation and validation of the positive and negative social exchange scale in older adults with disabilities in China.

PURPOSE: This study translated the Positive and Negative Social Exchange (PANSE) scale into Chinese, examined its psychometric characteristics, and explored its feasibility for use among older adults with disabilities from China. MATERIALS AND METHODS: A two-stage study procedure was employed. In the first stage, the English version of the PANSE scale was translated and cross-culturally adapted. In the second stage, the reliability and validity of the scale were assessed based on item-total correlation, internal consistency, test-retest reliability, content validity, structural validity, concurrent criterion validity, and known group validity. RESULTS: A total of 357 older adults with disabilities participated in the survey. The Chinese version of the PANSE scale consisted of two parts, the Positive Social Exchange Scale and the Negative Social Exchange Scale. Exploratory factor analysis extracted six communal factors. The cumulative contribution of the two parts of the scale was 69.90% and 77.88%, respectively. The item-total correlation was 0.353 to 0.802, the internal consistency of the PANSE was 0.653 to 0.886. The PANSE demonstrated good content validity and it was correlated with the SSRS scale. CONCLUSION: The Chinese version of the PANSE is a valid and reliable instrument for assessing social exchange in Chinese older adults with disabilities.Implication for rehabilitationDespite the growing number of older adults with disabilities being a concern in China, the lack of tools to measure the type of social support limits research related to the health status of these people.This study cross-culturally adapted, translated into Chinese and validated the Positive and Negative Social Exchange (PANSE) scale as the measurement tool to be used in the cultural context of China.The two subscales of PANSE were validated in the Chinese population of older adults with disabilities.The PANSE scale measures social exchange among older adults with disabilities in China, which can guide the development of interventions to address issues in the social exchange of these people.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

The Roles of Natural Alkaloids and Polyphenols in Lipid Metabolism: Therapeutic Implications and Potential Targets in Metabolic Diseases.

The prevalence of obesity and its associated diseases has increased dramatically, and they are major threats to human health worldwide. A variety of approaches, such as physical training and drug therapy, can be used to reduce weight and reverse associated diseases; however, the efficacy and the prognosis are often unsatisfactory. It has been reported that natural food-based small molecules can prevent obesity and its associated diseases. Among them, alkaloids and polyphenols have been demonstrated to regulate lipid metabolism by enhancing energy metabolism, promoting lipid phagocytosis, inhibiting adipocyte proliferation and differentiation, and enhancing the intestinal microbial community to alleviate obesity. This review summarizes the regulatory mechanisms and metabolic pathways of these natural small molecules and reveals that the binding targets of most of these molecules are still undefined, which limits the study of their regulatory mechanisms and prevents their further application. In this review, we describe the use of Discovery Studio for the reverse docking of related small molecules and provide new insights for target protein prediction, scaffold hopping, and mechanistic studies in the future. These studies will provide a theoretical basis for the modernization of anti-obesity drugs and promote the discovery of novel drugs.

Effects of transitional care based on the social support theory for older patients with osteoporotic vertebral compression fractures: A quasi-experimental trial.

OBJECTIVES: This study aimed to investigate the effects of transitional care (TC) programs on the health outcomes of discharged older patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: A total of 160 older patients were recruited from two campuses of a public teaching hospital in China. Patients were grouped according to the campus to which they were admitted. The TC programs commenced one day before discharge and lasted 6 months after discharge. Repeated-measures analysis of variance was used to analyse the effects of the TC programs. RESULTS: The TC programs improved the discharge of older patients with OVCF in their activities of daily living (ADLs), pain levels and social support, and decreased fracture recurrence rates. CONCLUSIONS: This study provides evidence of concurrent clinical improvements and health outcomes in discharged older patients with OVCFs from the effects of TC programs based on social support theory.

Novel Covert-Inferior Pelvic Approach with a Subpubic Plate for Anterior Pelvic Ring Fractures: Preliminary Results.

BACKGROUND: Anterior pelvic ring injuries can be treated via Pfannenstiel, modified Stoppa, or ilioinguinal approaches, but these require exposing the abdominal soft tissues and may damage pelvic organs. The scar on the abdominal wall is also unacceptable for some patients. The minimally invasive anterior pelvic ring internal fixator (INFIX) is not ideal for thin patients with easily irritated skin, and it is associated with complications such as femoral nerve palsy, vascular occlusion, and lateral femoral cutaneous nerve injury. In this study, we designed a new external pelvic approach for the treatment of an anterior pelvic ring fracture. METHODS: We retrospectively reviewed 28 patients with 36 pubic ramus fractures that had been treated via the covert-inferior pelvic approach. All patients underwent a surgical procedure between August 2019 and January 2021. According to the Nakatani classification, there were 6 cases of type-I fracture, 25 cases of type-II fracture, and 5 cases of type-III fracture. Operative time, blood loss, and postoperative radiographic and computed tomographic (CT) findings were recorded. Patients were followed for fracture healing time, functional status, esthetic satisfaction, and complications. RESULTS: A total of 27 patients had follow-up for at least 12 months (range, 12 to 29 months). Postoperative radiographs and CT scans showed well-positioned plates and screws. The mean preoperative time was 9.4 ± 3.8 days, the mean operative time was 61.3 ± 22.67 minutes, the mean intraoperative blood loss was 63.6 ± 42.62 mL, the mean fracture healing time was 4.1 ± 1.6 months, and the mean Majeed score was 89.74 ± 8.07. There were no complications of nonunion, internal fixation failure, vascular injury, nerve palsy, or hernia. All of the patients were esthetically satisfied with the scar. CONCLUSIONS: The covert-inferior pelvic approach combined with a subpubic plate effectively fixed Nakatani type-I, II, and III fractures. The advantages of this method include rapid recovery after the surgical procedure, safety, simplicity, a short learning curve, no damage to abdominal soft tissue, no effect on pubic symphysis micromotion, and esthetic benefits. It may be another option for anterior pelvic ring fractures and can supplement other approaches. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Effects of internet-based interventions on improvement of glycemic control and self-management in older adults with diabetes: Systematic review and meta-analysis.

PURPOSE: To assess and summarize the effects of internet-based interventions on diabetes control and self-management of older adults with diabetes. METHODS: PubMed, Web of Science and three Chinese databases were searched to identified articles published in until December 2021. Clinical trials if they covered the effects of internet-based interventions on diabetes control and self-management of older adults with diabetes were included. All data analysis were performed by Review Manager 5.3. RESULTS: Sixteen studies with a total of 5604 participants met the inclusion criteria. Our primary outcomes included HbA1c control and self-management. (1) HbA1c control: results indicated statistically difference and high heterogeneity [Q = 112.9, df = 8, p < 0.001, I2 = 93%], in the subgroup analysis of studies in China, results showed a significant influence of internet-based interventions on HbA1c control [Q = 21.31, df = 5, p = 0.03, I2 = 77%]; (2) self-management: in the subgroup analysis of study duration ≤ 6 months [Q = 84.62, df = 2, p < 0.001, I2 = 98%]. CONCLUSION: Internet-based interventions are promising on diabetes control and self-management of older adults with diabetes, but still preliminary due to the heterogeneity of intervention components and the limited number of higher methodological quality trials. AVAILABILITY OF DATA AND MATERIAL: Applicable.

Effects of an emotional support programme on older adults living in nursing homes: A quasi-experimental study.

This study aimed to examine the feasibility and validity of an emotional support programme developed for older adults living in nursing homes, using a quasi-experimental design. Older adults in the intervention group attended a 12-week emotional support programme while those in the control group received usual care. Outcome variables, assessed at baseline and at 1-month and 3-month follow ups, included nursing home adjustment, perceived social support, and quality of life. Group-by-time interaction effects were found concerning nursing home adjustment and perceived social support. Significant improvements in the two variables were observed in the intervention group, but no significant difference was found in quality of life. The emotional support programme based on social learning theory resulted in significant improvements in nursing home adjustment and perceived social support. To respond to the demands of an ageing society, further studies are needed on this topic.

A New lncRNA, lnc-LLMA, Regulates Lipid Metabolism in Pig Hepatocytes.

A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.

CTCF: A novel fusion partner of ETO2 in a multiple relapsed acute myeloid leukemia patient.

ETO2 is a nuclear co-repressor, which plays a critical role in the regulation of the cell cycle, self-renewal capacity, and differentiation of hematopoietic progenitor cells. We identified novel fusion transcripts involving ETO2 and CTCF by RNA-seq in a multiple relapsed AML case. The CTCF-ETO2 and ETO2-CTCF chimeric genes were validated by RT-PCR and Sanger sequencing. In addition, both transcripts apparently promoted cell proliferation via JAK/STAT3 pathway that is sensitive to STAT3 inhibitors. The novel fusions may have prognostic value and pathogenic mechanisms in acute myeloid leukemia.

Translatomics Probes Into the Role of Lycopene on Improving Hepatic Steatosis Induced by High-Fat Diet.

Liver is an important organ for fat metabolism. Excessive intake of a high-fat/energy diet is a major cause of hepatic steatosis and its complications such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Supplementation with lycopene, a natural compound, is effective in lowering triglyceride levels in the liver, although the underlying mechanism at the translational level is unclear. In this study, mice were fed a high-fat diet (HFD) to induce hepatic steatosis and treated with or without lycopene. Translation omics and transcriptome sequencing were performed on the liver to explore the regulatory mechanism of lycopene in liver steatosis induced by HFD, and identify differentially expressed genes (DEGs). We identified 1,358 DEGs at the translational level. Through transcriptomics and translatomics joint analysis, we narrowed the range of functional genes to 112 DEGs and found that lycopene may affect lipid metabolism by regulating the expression of LPIN1 at the transcriptional and translational levels. This study provides a powerful tool for translatome and transcriptome integration and a new strategy for the screening of candidate genes.

Integrative ATAC-seq and RNA-seq Analysis of the Longissimus Muscle of Luchuan and Duroc Pigs.

Luchuan pig is a typical obese pig breed in China, and the diameter and area of its longissimus dorsi muscle fibers are significantly smaller than those of Duroc (lean) pig. Skeletal muscle fiber characteristics are related to meat quality of livestock. There is a significant correlation between the quality of different breeds of pork and the characteristics of muscle fiber, which is an important factor affecting the quality of pork. The diameter and area of muscle fibers are related to muscle growth and development. Therefore, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analysis to investigate the potential mechanism underlying the difference in skeletal muscle growth and development between the two types of pigs. First, transposase-accessible chromatin was analyzed to map the landscape of open chromatin regions and transcription factor binding sites. We identified several transcription factors that potentially affected muscle growth and development, including TFAP4, MAX, NHLH1, FRX5, and TGIF1. We also found that transcription factors with basic helix-loop-helix structures had a preference for binding to genes involved in muscle development. Then, by integrating ATAC-seq and RNA-seq, we found that the Wnt signaling pathway, the mTOR signaling pathway, and other classical pathways regulate skeletal muscle development. In addition, some pathways that might regulate skeletal muscle growth, such as parathyroid hormone synthesis, secretion, and action, synthesis and degradation of ketone bodies, and the thyroid hormone signaling pathway, which were significantly enriched. After further study, we identified a number of candidate genes (ASNS, CARNS1, G0S2, PPP1R14C, and SH3BP5) that might be associated with muscle development. We also found that the differential regulation of chromatin openness at the level of some genes was contrary to the differential regulation at the level of transcription, suggesting that transcription factors and transcriptional repressors may be involved in the regulation of gene expression. Our study provided an in-depth understanding of the mechanism behind the differences in muscle fibers from two species of pig and provided an important foundation for further research on improving the quality of pork.

Integrated Transcriptomic and Translatomic Inquiry of the Role of Betaine on Lipid Metabolic Dysregulation Induced by a High-Fat Diet.

An excessive high-fat/energy diet is a major cause of obesity and linked complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of mRNA sequencing and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates liver lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of transcriptome and translatome, we found that betaine had the greater effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP51A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrated betaine alleviating lipid metabolic dysfunction at the translational level. The transcriptome and translatome data integration approach used herein provides for a new understanding of the means by which to treat NAFLD.

Translatome analysis reveals the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (mRNAs bound to ribosome-nascent chain complex sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet adding betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism-associated genes were differentially expressed at translational level, for example. And the translation ratio (TR) of gene significantly increased after betaine treatment. Finally, we identified a novel function gene, Gpc1, which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD.