Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity. METHODS: We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity. RESULTS: A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08]. CONCLUSIONS: This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.

N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/ß-catenin signal pathway.

BACKGROUND: Wnt/FZD-mediated signaling pathways are activated in more than 90% of hepatocellular carcinoma (HCC) cell lines. As a well-known secretory glycoprotein, Wnt3 can interact with FZD receptors on the cell surface, thereby activating the Wnt/ß-catenin signaling pathway. However, the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still unclear. AIM: To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC cells. METHODS: Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites, actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation, the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy, and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/ß-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function experiments. RESULTS: Wnt3 has two N-glycosylation-modified sites (Asn90 and Asn301); when a single site at amino acid 301 is mutated, the stability of Wnt3 is weakened; the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously; and the level of proteins related to the Wnt/ß-catenin signaling pathway is downregulated. Cell proliferation, migration and invasion are also weakened in the case of single 301 site and double-site mutations. CONCLUSION: These results indicate that by inhibiting the N-glycosylation of Wnt3, the proliferation, migration, invasion and colony formation abilities of liver cancer cells can be weakened, which might provide new therapeutic strategies for clinical liver cancer in the future.

Peroxiredoxin 4 deficiency induces accelerated ovarian aging through destroyed proteostasis in granulosa cells.

Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4-/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4-/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Meta-analysis of new intervention measures for preventing side effects of artificial joint replacement.

BACKGROUND: Intertrochanteric fracture of the femur occurs mostly among older people, and seriously affects daily life and quality of life. At present, physical intervention, drug treatment, routine intervention and rehabilitation training are widely used for prevention of side effects, but it is still inconclusive which intervention has the best effect. AIM: To compare the effects of new intervention measures for preventing side effects of artificial joint replacement. METHODS: We searched the Chinese and English literatures for comparative studies on the prevention of side effects of new interventions for artificial joint replacement from July 2013 to June 2023 in China HowNet, PubMed, Wanfang, Weipu and other databases. Study quality was evaluated by improved Jadad scoring standard, and the effects of different interventions on preventing different complications were analyzed by meta-analysis of evidence-based medicine with Review Manager 5.0 software. RESULTS: Ten articles, including 869 cases, were finally included. The preventive effects of different interventions on the side effects of artificial joint replacement were studied, and valid data were extracted. There were two articles on the preventive effects of drug intervention, four on comparison of the preventive effects of combined and single interventions, and three on the preventive effects of physical intervention, rehabilitation training and routine intervention. Meta-analysis showed that the preventive effect of rivaroxaban was significantly better than low molecular weight heparin calcium [mean difference (MD) = -0.16, 95%CI: -0.28 to -0.04, P < 0.05]. The effect of combined intervention was significantly better than that of single intervention (MD = -0.08, 95%CI: -0.16 to -0.01, P < 0.001). Physical intervention was significantly better than routine intervention and rehabilitation training (MD = 0.26, 95%CI: 0.16-0.36, P < 0.001). CONCLUSION: Rivaroxaban combined with rehabilitation training is preferred for preventing deep vein thrombosis after artificial joint replacement. In the prevention of pulmonary embolism, rivaroxaban drug intervention is given priority. The effect of combined intervention is better than that of single intervention.

High methylation of the same promoter of lncRNA ZNF582-AS1/ZNF582 promotes malignant progression of esophageal cancer.

Aim: This study aimed to investigate the functions of ZNF582-AS1 and ZNF582 in esophageal cancer (EC). Materials & methods: Bioinformatics analysis, qRT-PCR and western blot were used to analyze the expression levels. Biological functions were evaluated using cell-counting kit 8, colony formation, Transwell assays and flow cytometry. FISH was used to detect subcellular localization, and methylation-specific PCR determined gene methylation levels. Animal experiments validated the impact on tumor progression. Results: ZNF582-AS1 and ZNF582 were highly methylated and downregulated in EC. Overexpression of ZNF582-AS1 up-regulated the expression of ZNF582, thereby inhibiting EC cell viability and metastasis, promoting apoptosis and inhibiting tumor growth. Conclusion: Low expression of ZNF582-AS1/ZNF582 mediated by DNA hypermethylation facilitates the malignant progression of EC.

Promoter hypermethylation silences ZNF582-AS1 and ZNF582, driving esophageal cancer progression, which has the potential for novel therapeutic strategies. # Methylation # Esophageal Cancer.

Norepinephrine regulates TNF expression via the A1AR-p38 MAPK-Relish pathway in granulocytes of oyster Crassostrea gigas.

Norepinephrine (NE) is involved in regulating cytokine expression and phagocytosis of immune cells in the innate immunity of vertebrates. In the present study, the modulation mechanism of NE on the biosynthesis of TNFs in oyster granulocytes was explored. The transcripts of CgTNF-1, CgTNF-2 and CgTNF-3 were highly expressed in granulocytes, and they were significantly up-regulated after LPS stimulation, while down-regulated after NE treatment. The phagocytic rate and apoptosis index of oyster granulocytes were also triggered by LPS stimulation and suppressed by NE treatment. The mRNA expressions of CgMAPK14 and CgRelish were significantly induced after NE treatment, and the translocation of CgRelish from cytoplasm to nucleus was observed. The concentration of intracellular Ca2+ in granulocytes was significantly up-regulated upon NE incubation, and this trend reverted after the treatment with DOX (specific antagonist for NE receptor, CgA1AR-1). No obvious significance was observed in intracellular cAMP concentrations in the PBS, NE and NE + DOX groups. Once CgA1AR-1 was blocked by DOX, the mRNA expressions of CgMAPK14 and CgRelish were significantly inhibited, and the translocation of CgRelish from cytoplasm to nucleus was also dramatically suppressed, while the mRNA expression of CgTNF-1 and the apoptosis index increased significantly to the same level with those in LPS group, respectively. These results collectively suggested that NE modulated TNF expression in oyster granulocyte through A1AR-p38 MAPK-Relish signaling pathway.

Rapid Mold Detection in Chinese Herbal Medicine Using Enhanced Deep Learning Technology.

Mold contamination poses a significant challenge in the processing and storage of Chinese herbal medicines (CHM), leading to quality degradation and reduced efficacy. To address this issue, we propose a rapid and accurate detection method for molds in CHM, with a specific focus on Atractylodes macrocephala, using electronic nose (e-nose) technology. The proposed method introduces an eccentric temporal convolutional network (ETCN) model, which effectively captures temporal and spatial information from the e-nose data, enabling efficient and precise mold detection in CHM. In our approach, we employ the stochastic resonance (SR) technique to eliminate noise from the raw e-nose data. By comprehensively analyzing data from eight sensors, the SR-enhanced ETCN (SR-ETCN) method achieves an impressive accuracy of 94.3%, outperforming seven other comparative models that use only the response time of 7.0 seconds before the rise phase. The experimental results showcase the ETCN model's accuracy and efficiency, providing a reliable solution for mold detection in Chinese herbal medicine. This study contributes significantly to expediting the assessment of herbal medicine quality, thereby helping to ensure the safety and efficacy of traditional medicinal practices.

Adherence to a Mediterranean diet is associated with a lower risk of diabetic kidney disease among individuals with hyperglycemia: a prospective cohort study.

BACKGROUND: Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). METHODS: We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. RESULTS: Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. CONCLUSIONS: In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

Notoginseng leaf triterpenes promotes angiogenesis by activating the Nrf2 pathway and AMPK/SIRT1-mediated PGC-1/ERα axis in ischemic stroke.

Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.

The characteristics of brain atrophy prior to the onset of Alzheimer's disease: a longitudinal study.

Objective: We aimed to use the onset time of Alzheimer's disease (AD) as the reference time to longitudinally investigate the atrophic characteristics of brain structures prior to the onset of AD. Materials and methods: A total of 328 participants from the ADNI database with clear onset of AD and structural imaging data were included in our study. The time before the onset of AD (abbreviated as BAD) was calculated. We investigated the longitudinal brain changes in 97 regions using multivariate linear mixed effects regression models. Results: The average BAD was -28.15 months, with a range from -156 to 0 months. The 54 brain regions showed significant atrophy prior to the onset of AD, and these regions were mainly distributed in the frontal and temporal lobes. The parietal and occipital lobe exhibited relatively less atrophy than the other brain lobes. Sex, age, and magnetic field strength had greater direct impacts on structural indicators than APOE genotype and education. The analysis of interaction effects revealed that the APOE ε4 mutation carriers exhibited more severe structural changes in specific brain regions as the BAD increased. However, sex, age, and education had minimal regulatory influence on the structural changes associated with BAD. Conclusion: Longitudinal analysis, with the onset time point of AD as the reference, can accurately describe the features of structural changes preceding the onset of AD and provide a comprehensive understanding of AD development.

High-Throughput Screening Strategy for Electrocatalysts for Selective Catalytic Oxidation of Formaldehyde to Formic Acid.

Electrocatalytic oxidation of formaldehyde (FOR) is an effective way to prevent the damage caused by formaldehyde and produce high-value products. A screening strategy of a single-layer MnO2-supported transition metal catalyst for the selective oxidation of formaldehyde to formic acid was designed by high-throughput density functional calculation. N-MnO2@Cu and MnO2@Cu are predicted to be potential FOR electrocatalysts with potential-limiting steps (PDS) of 0.008 and -0.009 eV, respectively. Electronic structure analysis of single-atom catalysts (SACs) shows that single-layer MnO2 can regulate the spin density of loaded transition metal and thus regulate the adsorption of HCHO (Ead), and Ead is volcanically distributed with the magnetic moment descriptor -|mM - mH|. In addition, the formula quantifies Ead and |mM - mH| to construct a volcano-type descriptor α describing the PDS [ΔG(*CHO)]. Other electronic and structural properties of SACs and α are used as input features for the GBR method to construct machine learning models predicting the PDS (R2 = 0.97). This study hopes to provide some insights into FOR electrocatalysts.

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma.

BACKGROUND: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. METHODS: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. RESULTS: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. CONCLUSIONS: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Occurrence and characterization of viruses infecting Amorphophallus in Yunnan, China.

Viral diseases are becoming an important problem in Amorphophallus production due to the propagation of seed corms and their trade across regions. In this study, combined-High-Throughput Sequencing, RT-PCR, electron microscopy, and mechanical inoculation were used to analyze virus-like infected Amorphophallus samples in Yunnan province to investigate the distribution, molecular characterization, and diversity and evolution of Amorphophallus-infecting viruses including three isolates of dasheen mosaic virus and three orthotospoviruses: mulberry vein banding associated virus (MVBaV), tomato zonate spot virus (TZSV) and impatiens necrotic spot virus (INSV). The results showed that DsMV is the dominant virus infecting Amorphophallus, mixed infections with DsMV and MVBaV to Amorphophallus were quite common in Yunnan province, China. This is the first report on infection of Amorphophallus with MVBaV, TZSV, and impatiens necrotic spot virus (INSV) in China. This work will help to develop an effective integrated management strategy to control the spread of Amorphophallus viral diseases.

Novel insights into the glucose metabolic alterations of freshwater snails: a pathway to molluscicide innovation and snail control strategies.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Interfacial Accumulation and Stability Enhancement Effects Triggered by Built-in Electric Field of SnO2/LaOCl Nanofibers Boost Carbon Dioxide Electroreduction.

Constructing a built-in interfacial electric field (BIEF) is an effective approach to enhance the electrocatalysts performance, but it has been rarely demonstrated for electrochemical carbon dioxide reduction reaction (CO2RR) to date. Herein, for the first time, SnO2/LaOCl nanofibers (NFs) with BIEF is created by electrospinning, exhibiting a high Faradaic efficiency (FE) of 100% C1 product (CO and HCOOH) at -0.9--1.1 V versus reversible hydrogen electrode (RHE) and a maximum FEHCOOH of 90.1% at -1.2 VRHE in H-cell, superior to the commercial SnO2 nanoparticles (NPs) and LaOCl NFs. SnO2/LaOCl NFs also exhibit outstanding stability, maintaining negligible activity degradation even after 10 h of electrolysis. Moreover, their current density and FEHCOOH are almost 400 mA cm-2 at -2.31 V and 83.4% in flow-cell. The satisfactory CO2RR performance of SnO2/LaOCl NFs with BIEF can be ascribed to tight interface of coupling SnO2 NPs and LaOCl NFs, which can induce charge redistribution, rich active sites, enhanced CO2 adsorption, as well as optimized Gibbs free energy of *OCHO. The work reveals that the BIEF will trigger interfacial accumulation and stability enhancement effects in promoting CO2RR activity and stability of SnO2-based materials, providing a novel approach to develop stable and efficient CO2RR electrocatalysts.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Sinomenine attenuates pulmonary fibrosis by downregulating TGF-ß1/Smad3, PI3K/Akt and NF-κB signaling pathways.

BACKGROUND: Since COVID-19 became a global epidemic disease in 2019, pulmonary fibrosis (PF) has become more prevalent among persons with severe infections, with IPF being the most prevalent form. In traditional Chinese medicine, various disorders are treated using Sinomenine (SIN). The SIN's strategy for PF defense is unclear. METHODS: Bleomycin (BLM) was used to induce PF, after which inflammatory factors, lung histological alterations, and the TGF-/Smad signaling pathway were assessed. By administering various dosages of SIN and the TGF- receptor inhibitor SB-431,542 to human embryonic lung fibroblasts (HFL-1) and A549 cells, we were able to examine proliferation and migration as well as the signaling molecules implicated in Epithelial-Mesenchymal Transition (EMT) and Extra-Cellular Matrix (ECM). RESULTS: In vivo, SIN reduced the pathological changes in the lung tissue induced by BLM, reduced the abnormal expression of inflammatory cytokines, and improved the weight and survival rate of mice. In vitro, SIN inhibited the migration and proliferation by inhibiting TGF-ß1/Smad3, PI3K/Akt, and NF-κB pathways, prevented the myofibroblasts (FMT) of HFL-1, reversed the EMT of A549 cells, restored the balance of matrix metalloenzymes, and reduced the expression of ECM proteins. CONCLUSION: SIN attenuated PF by down-regulating TGF-ß/Smad3, PI3K/Akt, and NF-κB signaling pathways, being a potential effective drug in the treatment of PF.

Cell Cycle-Related Centromere Protein F Deficiency Suppresses Ovarian Cancer Cell Growth by Inducing Ferroptosis.

OBJECTIVES: This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis. DESIGN: The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]). RESULTS: By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis. LIMITATIONS: This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies. CONCLUSIONS: Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.

A predictive model for patent ductus arteriosus seven days postpartum in preterm infants: an ultrasound-based assessment of ductus arteriosus intimal thickness within 24†h after birth.

Objectives: To develop a predictive model for patent ductus arteriosus (PDA) in preterm infants at seven days postpartum. The model employs ultrasound measurements of the ductus arteriosus (DA) intimal thickness (IT) obtained within 24 h after birth. Methods: One hundred and five preterm infants with gestational ages ranging from 27.0 to 36.7 weeks admitted within 24 h following birth were prospectively enrolled. Echocardiographic assessments were performed to measure DA IT within 24 h after birth, and DA status was evaluated through echocardiography on the seventh day postpartum. Potential predictors were considered, including traditional clinical risk factors, M-mode ultrasound parameters, lumen diameter of the DA (LD), and DA flow metrics. A final prediction model was formulated through bidirectional stepwise regression analysis and subsequently subjected to internal validation. The model's discriminative ability, calibration, and clinical applicability were also assessed. Results: The final predictive model included birth weight, application of mechanical ventilation, left ventricular end-diastolic diameter (LVEDd), LD, and the logarithm of IT (logIT). The receiver operating characteristic (ROC) curve for the model, predicated on logIT, exhibited excellent discriminative power with an area under the curve (AUC) of 0.985 (95% CI: 0.966-1.000), sensitivity of 1.000, and specificity of 0.909. Moreover, the model demonstrated robust calibration and goodness-of-fit (χ2 value = 0.560, p > 0.05), as well as strong reproducibility (accuracy: 0.935, Kappa: 0.773), as evidenced by 10-fold cross-validation. A decision curve analysis confirmed the model's broad clinical utility. Conclusions: Our study successfully establishes a predictive model for PDA in preterm infants at seven days postpartum, leveraging the measurement of DA IT. This model enables identifying, within the first 24 h of life, infants who are likely to benefit from timely DA closure, thereby informing treatment decisions.