LINC00525 enhances ZNF460-regulated CD24 expression through the sponge miR-125a-5p to promote malignant progression of breast cancer.

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.

The effect of LNCRNA SHANK3 on the malignant development of gastric cancer cells by regulating the miR-4530/MNX1.

Gastric cancer (GC) has become the first malignant tumor with highest incidence rate and mortality of cancer in China, finding therapeutic targets for gastric cancer is of great significant for improving the survival rate of patients with GC. Recently, many of studies have shown that LncRNAs is involved in multiple biological progresses in the development of GC. This study, we screened for abnormally high expression of LncSHANK3 in GC through the TCGA database, and found that LncSHANK3 sponge adsorbs miR-4530, further competing with MNX1 and binding to miR-4530. We demonstrated the interaction between LncSHANK3 and miR-4530 through luciferase reporting analysis, with miR-4530 negatively regulating MNX1.Through CCK8, colony formation, transwell, and wound healing assays, it was found that LncSHANK3 affects the occurrence of GC through cell proliferation, migration and invasion. In conclusion, LncSHANK3/miR-4530/MNX1 axis is a potential mechanism for the treatment of GC.

Pindel-TD: A Tandem Duplication Detector Based on A Pattern Growth Approach.

Tandem duplication (TD) is a major type of structural variations (SVs) that plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most modern SV detection methods due to the lack of specialized operation on TD-related mutational signals. Herein, we developed a TD detection module for the Pindel tool, referred to as Pindel-TD, based on a TD-specific pattern growth approach. Pindel-TD is capable of detecting TDs with a wide size range at single nucleotide resolution. Using simulated and real read data from HG002, we demonstrated that Pindel-TD outperforms other leading methods in terms of precision, recall, F1-score, and robustness. Furthermore, by applying Pindel-TD to data generated from the K562 cancer cell line, we identified a TD located at the seventh exon of SAGE1, providing an explanation for its high expression. Pindel-TD is available for non-commercial use at https://github.com/xjtu-omics/pindel.

Preparation of Environmentally Friendly Oil- and Water-Resistant Paper Using Holo-Lignocellulosic Nanofibril (LCNF)-Based Composite Coating.

In the present study, an environmentally friendly oil- and water-resistant paper was developed using a holo-lignocellulosic nanofibril (LCNF)-based composite coating. The LCNF was prepared from wheat straw using a biomechanical method. Characterizations of oil- and water-resistant coated paper and the effect of LCNF content on the performance of the coated paper were confirmed by combining contact angle analysis, Cobb 300s, and mechanical performance tests. The results show that the barrier performance and mechanical strength of the coated paper were greatly improved with the increase of LCNF content. The contact angle of oil and water of coated paper containing 50% LCNF were 69° and 78°, respectively, while the contact angle of oil and water of the base paper were only 30° and 20°, respectively. Cobb 300s values reduced from 110 g/m2 to 30 g/m2 when the LCNF content increased from 50% to 90%. Moreover, under the coating amount of 20 g/m2, the tensile strength of the coating paper was 0.980 KN/m, an increase of 10.11% compared with the base paper. The bursting strength reached 701.930 KPa, which was 10.75% higher than the base paper. In short, it is feasible to prepare LCNF from wheat straw, and apply it to produce water-proof and oil-proof paper. The water-proof and oil-proof paper developed in this study not only offers a novel approach to addressing white pollution but also presents a new research avenue for exploring the potential applications of agricultural waste.

Scoping review of obesity interventions: Research frontiers and publication status.

Obesity and overweight are significant global health issues, and numerous obesity intervention studies have been conducted. Summarizing current knowledge of interventions aims to inform researchers and policymakers to keep up-to-date with the latest scientific advancements and trends. In this review, we comprehensively retrieved and screened 4,541 studies on obesity intervention published between 2018 and 2022 in the Web of Science Core Collection, and objectively presented research frontiers using bibliometric analysis. The research frontiers of intervention are mainly focused on dietary, exercise, pharmacological interventions, bariatric surgery, environmental, and cognitive interventions. Time-restricted eating is the hottest research topic, followed by probiotics and Roux-en-Y gastric bypass. Gut microbiota is located in the "Basic and transversal themes" quadrant with a high centrality and low density, which has great development potentiality. Obesity intervention is becoming increasingly common,and we advocate for researchers to undertake more focused research endeavors that consider the specific characteristics of diverse populations or patients.

Aberrant activated Notch1 promotes prostate enlargement driven by androgen signaling via disrupting mitochondrial function in mouse.

The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide, the incidence of prostate diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), is on the rise and is gradually becoming a significant medical problem globally. The notch signaling pathway is essential in regulating prostate early development. However, the potential regulatory mechanism of Notch signaling in prostatic enlargement and hyperplasia remains unclear. In this study, we proved that overactivation of Notch1 signaling in mouse prostatic epithelial cells (OEx) led to prostatic enlargement via enhancing proliferation and inhibiting apoptosis of prostatic epithelial cells. Further study showed that N1ICD/RBPJ directly up-regulated the androgen receptor (AR) and enhanced prostatic sensitivity to androgens. Hyper-proliferation was not found in orchidectomized OEx mice without androgen supply but was observed after Dihydrotestosterone (DHT) supplementation. Our data showed that the number of mitochondrion in prostatic epithelial cells of OEx mice was increased, but the mitochondrial function was impaired, and the essential activity of the mitochondrial respiratory electron transport chain was significantly weakened. Disordered mitochondrial number and metabolic function further resulted in excessive accumulation of reactive oxygen species (ROS). Importantly, anti-oxidant N-Acetyl-L-Cysteine (NAC) therapy could alleviate prostatic hyperplasia caused by the over-activation of Notch1 signaling. Furthermore, we observed the incremental Notch signaling activity in progenitor-like club cells in the scRNA-seq data set of human BPH patients. Moreover, the increased number of TROP2+ progenitors and Club cells was also confirmed in our OEx mice. In conclusion, our study revealed that over-activated Notch1 signaling induces prostatic enlargement by increasing androgen receptor sensitivity, disrupting cellular mitochondrial metabolism, increasing ROS, and a higher number of progenitor cells, all of which can be effectively rescued by NAC treatment.

A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer.

BACKGROUND: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo. METHODS: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels. RESULTS: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH+ cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79. CONCLUSION: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics.

Ectopic expression of the Arabidopsis mutant L3 NB-LRR receptor gene in Nicotiana benthamiana cells leads to cell death.

Nucleotide-binding sites and leucine-rich repeat proteins (NLRs) act as critical intracellular immune receptors. Previous studies reported an Arabidopsis-resistant gene L3 (AT1G15890), which encoded a coiled-coil (CC) NLR that conferred cell death in bacteria; however, its function in planta remains unclear. This study describes a comprehensive structure-function analysis of L3 in Nicotiana benthamiana. The results of the transient assay showed that the L3 CC domain is sufficient for cell-death induction. The first 140 amino acid segment constituted the minimal function region that could cause cell death. The YFP-labeled L3 CC domain was localized to the plasma membrane, which was considered crucial for the function and self-interaction of the L3 CC domain. The results of point mutations analysis showed that L3 CC domain function is affected by mutations in some specific residues, and loss-of-function mutations in the CC domain affected the function of full-length L3. These study results offered considerable evidence to understand the activation mechanism of L3.

Efficacy and safety of transcranial direct current stimulation in the treatment of fibromyalgia: A systematic review and meta-analysis.

OBJECTIVES: To update a systematic review of the efficacy and safety of transcranial direct current stimulation (tDCS) for analgesia, for antidepressant effects, and to reduce the impact of fibromyalgia (FM), looking for optimal areas of stimulation. METHODS: We searched five databases to identify randomized controlled trials comparing active and sham tDCS for FM. The primary outcome was pain intensity, and secondary outcome measures included FM Impact Questionnaire (FIQ) and depression score. Meta-analysis was conducted using standardized mean difference (SMD). Subgroup analysis was performed to determine the effects of different regional stimulation, over the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), opercular-insular cortex (OIC), and occipital nerve (ON) regions. We analyzed the minimal clinically important difference (MCID) by the value of the mean difference (MD) for an 11-point scale for pain, the Beck Depressive Inventory-II (BDI-II), and the Fibromyalgia Impact Questionnaire (FIQ) score. We described the certainty of the evidence (COE) using the tool GRADE profile. RESULTS: Twenty studies were included in the analysis. Active tDCS had a positive effect on pain (SMD= -1.04; 95 % CI -1.38 to -0.69), depression (SMD= -0.46; 95 % CI -0.64 to -0.29), FIQ (SMD= -0.73; 95 % CI -1.09 to -0.36), COE is moderate. Only group M1 (SD=-1.57) and DLPFC (SD=-1.44) could achieve MCID for analgesia; For BDI-II, only group DLPFC (SD=-5.36) could achieve an MCID change. Adverse events were mild. CONCLUSION: tDCS is a safe intervention that relieves pain intensity, reduces depression, and reduces the impact of FM on life. Achieving an MCID is related to the stimulation site and the target symptom.

Hexaxial external fixator versus intramedullary nail in treating segmental tibial fractures: a retrospective study.

BACKGROUND: It's difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs. METHODS: A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit. RESULTS: There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P < 0.05), with bone union time for (6.9 ± 0.8) months and (7.7 ± 1.4) months, respectively(P < 0.05). There was no deep infection in both groups. In the HEF group and IMN group, mMPTA was (86.9 ± 1.5)° and (89.7 ± 1.8)°(P < 0.05), mPPTA was (80.8 ± 1.9)° and (78.6 ± 2.0)°(P < 0.05), mLDTA was (88.5 ± 1.7)° and (90.3 ± 1.7)°(P < 0.05), while mADTA was (80.8 ± 1.5)° and (78.4 ± 1.3)°(P < 0.05). No significant differences were found between the two groups at the last clinical visit concerning HSS knee joint score and AOFAS ankle joint score, ROM of flexion of keen joint and ROM of plantar flexion of ankle joint (P > 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P < 0.05). CONCLUSION: In terms of final clinical outcomes, the use of either HEF or IMN for STFs can achieve good therapeutic effects. While HEF is superior to IMN in terms of completely closed reduction, early full weight bearing, early bone union and alignment. Nevertheless, HEF has a greater impact on the ROM of dorsal flexion of the ankle joint, and much more care and adjustment are needed for the patients than IMN.

Advanced lung cancer inflammation index predicts overall survival of hepatocellular carcinoma after hepatectomy.

Aim: Limited data are available regarding ALI's clinical relevance and prognostic value in patients with hepatocellular carcinoma (HCC) after hepatectomy. Materials and methods: HCC patients who received hepatectomy at the Meizhou People's Hospital from May 2011 to February 2022 were enrolled in the study cohort. The ALI was calculated as follows: ALI = BMI (kg/m2) × ALB (g/dL)/(absolute neutrophil count/absolute lymphocyte count). The primary outcome was overall survival (OS). The secondary outcome was cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were performed, followed by nomogram construction and decision curve analysis (DCA). Results: 425 HCC patients were enrolled for analyses. Lower preoperative ALI was significantly correlated with incomplete tumor capsule and advanced tumor stage. Lower preoperative ALI was an adverse independent prognostic factor for OS (HR: 1.512, 95% CI: 1.122-2.039, P 0.007) and CSS (HR: 1.754, 95% CI: 1.262-2.438, P <0.001) in HCC patients. The nomogram plot was built based on three (including age, TNM stage, and ALI) and two (including TNM stage and ALI) independent prognostic factors for OS and CSS, respectively. Further analyses indicated that the nomogram had better predictive value and some net benefit than the traditional TNM stage alone, especially in long-term OS. Conclusions: Our study further indicated that ALI could be a prognostic marker for OS and CSS in HCC patients after hepatectomy, especially in long-term OS.

MAGE-A11 is a potential prognostic biomarker and immunotherapeutic target in gastric cancer.

Gastric cancer poses a serious threat to human health and affects the digestive system. The lack of early symptoms and a dearth of effective identification methods make diagnosis difficult, with many patients only receiving a definitive diagnosis at a malignant stage, causing them to miss out on optimal therapeutic interventions. Melanoma-associated antigen-A (MAGE-A) is part of the MAGE family and falls under the cancer/testis antigen (CTA) category. The MAGE-A subfamily plays a significant role in tumorigenesis, proliferation and migration. The expression, prognosis and function of MAGE-A family members in GC, however, remain unclear. Our research and screening have shown that MAGE-A11 was highly expressed in GC tissues and was associated with poor patient prognosis. Additionally, MAGE-A11 functioned as an independent prognostic factor in GC through Cox regression analysis, and its expression showed significant correlation with both tumour immune cell infiltration and responsiveness to immunotherapy. Our data further indicated that MAGE-A11 regulated GC cell proliferation and migration. Subsequently, our findings propose that MAGE-A11 may operate as a prognostic factor, having potential as an immunotherapy target for GC.

Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Effectiveness of a socioecological model-guided, smart device-based, self-management-oriented lifestyle intervention in community residents: protocol for a cluster-randomized controlled trial.

BACKGROUND: Healthy lifestyles are crucial for preventing chronic diseases. Nonetheless, approximately 90% of Chinese community residents regularly engage in at least one unhealthy lifestyle. Mobile smart devices-based health interventions (mHealth) that incorporate theoretical frameworks regarding behavioral change in interaction with the environment may provide an appealing and cost-effective approach for promoting sustainable adaptations of healthier lifestyles. We designed a randomized controlled trial (RCT) to evaluate the effectiveness of a socioecological model-guided, smart device-based, and self-management-oriented lifestyles (3SLIFE) intervention, to promote healthy lifestyles among Chinese community residents. METHODS: This two-arm, parallel, cluster-RCT with a 6-month intervention and 6-month follow-up period foresees to randomize a total of 20 communities/villages from 4 townships in a 1:1 ratio to either intervention or control. Within these communities, a total of at least 256 community residents will be enrolled. The experimental group will receive a multi-level intervention based on the socioecological model supplemented with a multi-dimensional empowerment approach. The control group will receive information only. The primary outcome is the reduction of modifiable unhealthy lifestyles at six months, including smoking, excess alcohol consumption, physical inactivity, unbalanced diet, and overweight/obesity. A reduction by one unhealthy behavior measured with the Healthy Lifestyle Index Score (HLIS) will be considered favorable. Secondary outcomes include reduction of specific unhealthy lifestyles at 3 months, 9 months, and 12 months, and mental health outcomes such as depression measured with PHQ-9, social outcomes such as social support measured with the modified Multidimensional Scale of Perceived Social Support, clinical outcomes such as obesity, and biomedical outcomes such as the development of gut microbiota. Data will be analyzed with mixed effects generalized linear models with family and link function determined by outcome distribution and accounting for clustering of participants in communities. DISCUSSION: This study will provide evidence concerning the effect of a mHealth intervention that incorporates a behavioral change theoretical framework on cultivating and maintaining healthy lifestyles in community residents. The study will provide insights into research on and application of similar mHealth intervention strategies to promote healthy lifestyles in community populations and settings. TRIAL REGISTRATION NUMBER: ChiCTR2300070575. Date of registration: April 17, 2023. https://www.chictr.org.cn/index.aspx .

7-Methoxy-13-dehydroxypaxilline: New indole diterpenoid from an endophytic fungus Penicillium sp. Nb 19.

ABSTACTA chemical investigation of the endophyte Penicillium sp. Nb 19, isolated from leaves of the traditionally medical plant Baphicacanthus cusia (Nees) Bremek., yielded one new indole diterpenoid, 7-methoxy-13-dehydroxypaxilline (1) together with seven known metabolites (2-8). The obtained structure of compound 1 was elucidated by its spectroscopic data. In addition, the absolute configuration of compound 6 was confirmed by ECD for the first time. Compounds 1-6 were evaluated for antitumor activity against MCF-7, HepG2, and HCCC-9810 cell lines.

ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression.

BACKGROUND: Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. METHODS: The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. RESULTS: ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. CONCLUSIONS: In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

Parental adherence to healthy lifestyles in relation to the risk of obesity in offspring: A prospective cohort study in China.

Background: While maternal adherence to a healthy lifestyle was shown to be associated with a lower risk of obesity in offspring, the potential role of overall parental lifestyles has not yet been explored. We aimed to address this gap by exploring whether parental adherence to an overall healthy lifestyle was associated with a lower risk of obesity in offspring. Methods: We included 5881 children and adolescents aged 6-15 years at enrolment in the 2010, 2012, and 2014 waves of the China Family Panel Studies (CFPS) who were free of obesity and followed them until 2020. Parental healthy lifestyle score at study baseline was composed of five modifiable lifestyle factors (0-5; 1 for each): never smoking, non-habitual drinking, weekly exercise, modified dietary diversity score ≥5 points, and body mass index (BMI) of 18.5-23.9 kg/m2. We defined obesity according to the age- and gender-specific cutoffs by the BMI percentile curves for Chinese children aged 6-18 years. We used multivariable Cox proportional hazard models to examine the association between parental healthy lifestyle score (both as continuous and categorical variables) and risk of offspring obesity. Results: Overall, 597 (10.2%) offspring developed obesity during a median follow-up of 6 years. Compared to the lowest tertile of parental healthy lifestyle score, participants in the highest tertile had a 42% (hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.45-0.74) lower risk of obesity. Both maternal (HR = 0.75; 95% CI = 0.61-0.92) and paternal (HR = 0.73; 95% CI = 0.60-0.89) healthy lifestyle scores were associated with lower risks of obesity in offspring. For specific lifestyle factors, we observed beneficial associations for paternal diverse diet (HR = 0.73; 95% CI = 0.60-0.88) and healthy BMI (HR = 0.65; 95% CI = 0.55-0.78). Conclusions: Adherence to an overall parental healthier lifestyle was associated with a lower risk of obesity in childhood and adolescence. This finding highlights the potential benefits of promoting a healthy lifestyle among parents for the primary prevention of offspring obesity.

Triglyceride-Glucose Index is Related to Carotid Artery Plaque in Railway Workers: A Cross-Sectional Study.

Aim: China has the highest rail transportation density in the world. Compared to other occupational populations, railway workers in China face increased risk of chronic non-communicable diseases. This study aims to investigate the relationship between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP) in a population of railway workers in southwest China. Methods: The cross-sectional study was conducted among 3169 railway workers who were categorized into four groups based on TyG index quartiles. The presence of CAP was assessed using carotid Doppler ultrasound. Logistic regression and restricted cubic spline analyses were used to estimate the association between TyG index and CAP, and subgroup analyses were performed based on age, blood pressure, metabolic dysfunction-associated fatty liver disease (MAFLD), smoking, drinking, and physical activity. Results: Participants with higher TyG index quartiles had a higher prevalence of CAP, with 11.63%, 14.11%, 20.20%, and 18.56% from the first to fourth quartile, respectively. The multi-adjusted logistic regression models showed a positive association between TyG index and the risk of CAP (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.06-1.41) when treated as a continuous variable. When analyzed as a categorical variable with increasing TyG index tertiles, the risk of CAP substantially increased with ORs (95% CIs) of 1.22 (0.90-1.65) for the second quartile, 1.70 (1.27-2.28) for the third quartile, and 1.46 (1.08-1.98) for the fourth quartile compared to the lowest quartile. Restricted cubic spline revealed that the association gradually strengthened with the increase of the TyG index below 9.56. Conclusion: TyG index was significantly associated with CAP, notably in populations with elevated quartiles of TyG index among railway workers. Monitoring the TyG index could be a useful risk management strategy for CAP in occupation population.

Metabolomics and Transcriptomics Analyses Reveals the Molecular Regulatory Mechanisms of Walnut (Juglans regia L.) Embryos in Response to Shade Treatment.

The walnut is an important nut that has numerous uses worldwide. However, due to dwarf and close plantation methods as well as continuous cloudy or rainy days that occur during periods of walnut oil accumulation, the walnut fruit exhibits varying degrees of stress under low-light conditions. However, the effects of shade on metabolites and genes in walnut embryos remain unclear in the literature. The purpose of this study is to investigate the lipid biosynthesis process that occurs in walnut embryos under shade treatment via the use of metabolomics and transcriptomics analyses. The results indicate that the oil content decreases significantly under shaded conditions, while the protein content increases significantly. The expression levels of fatty acid desaturase 2 (FAD2) and stearoyl-ACP-desaturase (SAD) involved in the lipid biosynthesis mechanism were significantly reduced in the shaded group, which resulted in reductions in oleic (C18:1), linoleic (C18:2), and α-linolenic (C18:3) acids. The reduced oil content was consistent with the downregulation of genes associated with the lipid biosynthesis mechanism. In the amino acid biosynthesis process, the upregulated cysteine synthase (cscK) and anthranilate synthase beta subunit 2 (trpG) genes promoted the accumulation of L-aspartic acid and L-citrulline. The increase in protein content was consistent with the upregulation of genes related to amino acid biosynthesis. Thus, our study provides new insights into the regulatory mechanisms of shade underlying overall walnut fruit quality.