Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II.

Background: The standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms. Methods: A model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides. Results: PM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II. Conclusion: Silibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.

Effects of porosity distribution on mechanical properties and osseointegration of porous polyetheretherketone.

Porous polyetheretherketone (P-PEEK) is widely used as the material for making implant screws, and yet its mechanical properties and osseointegration for ultilization are still unsatisfied. In this work, the effects of the porosity distribution on the mechanical properties and osseointegration were investigated. Functionally graded P-PEEK (FGP-PEEK) and uniform P-PEEK (UP-PEEK) were developed by infiltration casting technology. The mechanical properties of the P-PEEK were studied by compressive and bending tests, and the osseointegration was evaluated by in vitro and rabbit femur experiments. The prepared FGP-PEEK was composed of the central dense part and its surrounding porous one where the pores were isodiametric and interconnected. Both the compressive strength and bending strength of the FGP-PEEK with graded porosity were higher than those of the UP-PEEK with uniform porosity. The mechanical properties of the FGP-PEEK were comparable to that of the human cancellous bone. The in vitro and in vivo experiments indicated the FGP-PEEK had no cytotoxicity, and its osseointegration was better than the UP-PEEK. The results demonstrated that the graded porosity had a superiority in the mechanical properties and osseointegration of the P-PEEK scaffolds compared to the uniform porosity. The influencing mechanisms of the porosity distribution on the mechanical properties and osseointegration were also clarified. Additionally, the osseointegration of the FGP-PEEK gradually increased as the surface porosity increased from 30 % to 50 %. The 50 %-surface porosity FGP-PEEK was a promising material on the application of the implant screws.

Comparison of three objective nutritional screening tools for identifying GLIM-defined malnutrition in patients with gastric cancer.

OBJECTIVE: This study aimed to compare three objective nutritional screening tools for identifying GLIM-defined malnutrition in patients with gastric cancer (GC). METHOD: Objective nutritional screening tools including geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were evaluated in patients with GC at our institution. Malnutrition was diagnosed according to the GLIM criteria. The diagnostic value of GNRI, PNI, and COUNT scores in identifying GLIM-defined malnutrition was assessed by conducting Receiver Operating Characteristic (ROC) curves and calculating the area under the curve (AUC). Additionally, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were determined. The Kappa coefficient (k) was used to assess agreement between three objective nutritional screening tools and GLIM criteria. RESULTS: A total of 316 patients were enrolled in this study, and malnutrition was diagnosed in 151 (47.8%) patients based on the GLIM criteria. The GNRI demonstrated good diagnostic accuracy (AUC = 0.805, 95% CI: 0.758-0.852) for detecting GLIM-defined malnutrition, while the PNI and COUNT score showed poor diagnostic accuracy with AUCs of 0.699 (95% CI: 0.641-0.757) and 0.665 (95% CI: 0.605-0.725) respectively. Among these objective nutritional screening tools, the GNRI-based malnutrition risk assessment demonstrated the highest specificity (80.0%), accuracy (72.8%), PPV (74.8%), NPV (71.4%), and consistency (k = 0.452) with GLIM-defined malnutrition. CONCLUSIONS: Compared to PNI and COUNT scores, GNRI demonstrated superior performance as an objective nutritional screening tool for identifying GLIM-defined malnutrition in GC patients.

Immunological roles for resistin and related adipokines in obesity-associated tumors.

Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.

Exploring the shared biomarkers between cardioembolic stroke and atrial fibrillation by WGCNA and machine learning.

Background: Cardioembolic Stroke (CS) and Atrial Fibrillation (AF) are prevalent diseases that significantly impact the quality of life and impose considerable financial burdens on society. Despite increasing evidence of a significant association between the two diseases, their complex interactions remain inadequately understood. We conducted bioinformatics analysis and employed machine learning techniques to investigate potential shared biomarkers between CS and AF. Methods: We retrieved the CS and AF datasets from the Gene Expression Omnibus (GEO) database and applied Weighted Gene Co-Expression Network Analysis (WGCNA) to develop co-expression networks aimed at identifying pivotal modules. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared genes within the modules related to CS and AF. The STRING database was used to build a protein-protein interaction (PPI) network, facilitating the discovery of hub genes within the network. Finally, several common used machine learning approaches were applied to construct the clinical predictive model of CS and AF. ROC curve analysis to evaluate the diagnostic value of the identified biomarkers for AF and CS. Results: Functional enrichment analysis indicated that pathways intrinsic to the immune response may be significantly involved in CS and AF. PPI network analysis identified a potential association of 4 key genes with both CS and AF, specifically PIK3R1, ITGAM, FOS, and TLR4. Conclusion: In our study, we utilized WGCNA, PPI network analysis, and machine learning to identify four hub genes significantly associated with CS and AF. Functional annotation outcomes revealed that inherent pathways related to the immune response connected to the recognized genes might could pave the way for further research on the etiological mechanisms and therapeutic targets for CS and AF.

The AST/ALT ratio predicts survival and improves oncological therapy decisions in patients with non-small cell lung cancer receiving immunotherapy with or without radiotherapy.

Background and purpose: Immunotherapy, with or without radiotherapy (iRT or ICIs-nonRT), is the standard treatment for non-small cell lung cancer (NSCLC). Nonetheless, the response to the treatment varies among patients. Given the established role of aspartate aminotransferase/alanine transaminase (AST/ALT) ratio in predicting cancer prognosis, we sought to identify whether the pre-treatment AST/ALT ratio has the potential to serve as a prognostic factor for NSCLC patients receiving ICIs-nonRT and iRT. Materials and methods: We retrospectively analyzed NSCLC patients who received immunotherapy between April 2018 and March 2021. Patients were classified into iRT group and ICIs-nonRT group and further classified based on AST/ALT ratio cut-off values. The Kaplan-Meier (KM) method estimated the time-to-event endpoints (progression-free survival (PFS) and overall survival (OS). Results: Of the cohort, 239 underwent ICIs-nonRT and 155 received iRT. Higher AST/ALT ratios correlated with worse outcomes in the ICIs-nonRT group but indicated better outcomes in those who received iRT. Multivariate analysis validated AST/ALT ratio as an independent prognostic factor. For AST/ALT ratios between 0.67-1.7, both ICIs-nonRT and iRT yielded similar treatment outcomes; with AST/ALT ratios greater than 1.7, iRT could be a more favorable treatment option (P=0.038). Conversely, for ratios less than 0.67, ICIs-nonRT could be a more favorable treatment option (P=0.073). Conclusions: The pre-treatment AST/ALT ratio demonstrates potential as a prognostic marker for treatment outcomes in NSCLC patients receiving either ICIs-nonRT or iRT. This finding could help guide clinicians in selecting more effective treatment protocols, thereby enhancing patient prognosis.

CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation.

AIMS: As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC). METHODS: In vitro and in vivo models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network. RESULTS: CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation. CONCLUSIONS: Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.

Dickeya fangzhongdai was prevalent and caused taro soft rot when coexisting with the Pectobacterium complex, with a preference for Araceae plants.

Bacterial soft rot caused by coinfection with Dickeya spp. and Pectobacterium spp. in hosts can cause successive changes in fields, and it is difficult to prevent the spread of and control the infection. Pectobacterium spp. are prevalent in the growing areas of tuberous crops, including taro and potato. Recently, Dickeya fangzhongdai has emerged as a virulent pathogen in taro. To determine the prevalence status of the causal agents and evaluate the potential spreading risks of D. fangzhongdai, screening and taxonomic classification were performed on phytopathogenic bacteria collected from different taro-growing areas in Guangdong Province, China, and biological and genomic characteristics were further compared among typical strains from all defined species. The causative agents were verified to be phytobacterial strains of D. fangzhongdai, Pectobacterium aroidearum and Pectobacterium colocasium. P. aroidearum and P. colocasium were found to form a complex preferring Araceae plants and show intensive genomic differentiation, indicating their ancestor had adapted to taro a long time prior. Compared with Pectobacterium spp., D. fangzhongdai was more virulent to taro corms under conditions of exogenous infection and more adaptable at elevated temperatures. D. fangzhongdai strains isolated from taro possessed genomic components of additional T4SSs, which were accompanied by additional copies of the hcp-vgrG genes of the T6SS, and these contributed to the expansion of their genomes. More gene clusters encoding secondary metabolites were found within the D. fangzhongdai strains than within the Pectobacterium complex; interestingly, distinct gene clusters encoding zeamine and arylpolyene were both most similar to those in D. solani that caused potato soft rot. These comparisons provided genomic evidences for that the newly emerging pathogen was potentially equipped to compete with other pathogens. Diagnostic qPCR verified that D. fangzhongdai was prevalent in most of the taro-growing areas and coexisted with the Pectobacterium complex, while the plants enriching D. fangzhongdai were frequently symptomatic at developing corms and adjacent pseudostems and caused severe symptoms. Thus, the emerging need for intensive monitoring on D. fangzhongdai to prevent it from spreading to other taro-growing areas and to other tuberous crops like potato; the adjustment of control strategies based on different pathopoiesis characteristics is recommended.

A novel role of AURKA kinase in erythroblast enucleation.

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection.

BACKGROUND: Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown. METHODS: Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy. RESULTS: The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720. CONCLUSIONS: Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).

Tuberoplasty reduces resistance force in dynamic shoulder abduction for irreparable rotator cuff tears: a cadaveric biomechanical study.

BACKGROUND: Arthroscopic tuberoplasty is an optional technique for managing irreparable rotator cuff tears. However, there is a lack of studies investigating the resistance force during shoulder abduction in cases of irreparable rotator cuff tears and tuberoplasty. HYPOTHESES: In shoulders with irreparable rotator cuff tears, impingement between the greater tuberosity (GT) and acromion increases the resistance force during dynamic shoulder abduction. Tuberoplasty is hypothesized to reduce this resistance force by mitigating impingement. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric shoulders, with a mean age of 67.75 years (range, 63-72 years), were utilized. The testing sequence included intact rotator cuff condition, irreparable rotator cuff tears (IRCTs), burnishing tuberoplasty, and prosthesis tuberoplasty. Burnishing tuberoplasty refers to the process wherein osteophytes on the GT are removed using a bur, and the GT is subsequently trimmed to create a rounded surface that maintains continuity with the humeral head. Deltoid forces and actuator distances were recorded. The relationship between deltoid forces and actuator distance was graphically represented in an ascending curve. Data were collected at five points within each motion cycle, corresponding to actuator distances of 20 mm, 30 mm, 40 mm, 50 mm, and 60 mm. RESULTS: In the intact rotator cuff condition, resistance forces at the five points were 34.25 ± 7.73 N, 53.75 ± 7.44 N, 82.50 ± 14.88 N, 136.25 ± 30.21 N, and 203.75 ± 30.68 N. In the IRCT testing cycle, resistance forces were 46.13 ± 7.72 N, 63.75 ± 10.61 N, 101.25 ± 9.91 N, 152.5 ± 21.21 N, and 231.25 ± 40.16 N. Burnishing tuberoplasty resulted in resistance forces of 32.25 ± 3.54 N, 51.25 ± 3.54 N, 75.00 ± 10.69 N, 115.00 ± 10.69 N, and 183.75 ± 25.04 N. Prosthesis tuberoplasty showed resistance forces of 29.88 ± 1.55 N, 49.88 ± 1.36 N, 73.75 ± 7.44 N, 112.50 ± 7.07 N, and 182.50 ± 19.09 N. Both forms of tuberoplasty significantly reduced resistance force compared to IRCTs. Prosthesis tuberoplasty further decreased resistance force due to a smooth surface, although the difference was not significant compared to burnishing tuberoplasty. CONCLUSION: Tuberoplasty effectively reduces resistance force during dynamic shoulder abduction in irreparable rotator cuff tears. Prosthesis tuberoplasty does not offer a significant advantage over burnishing tuberoplasty in reducing resistance force. CLINICAL RELEVANCE: Tuberoplasty has the potential to decrease impingement, subsequently reducing resistance force during dynamic shoulder abduction, which may be beneficial in addressing conditions like pseudoparalysis.

Arthroscopic Resection for Extra-articular Ganglion Cysts of Gastrocnemius Near Vessels.

Extra-articular ganglion cysts arising from the gastrocnemius tendon near popliteal vessels can cause pain and claudication. Open resection of this kind of cyst has been described frequently because the vessels can be well protected with a retractor. However, it's a challenge to remove cysts that are near vessels under arthroscopy, because a retractor cannot be used in arthroscopic surgery. This article will report a method of arthroscopic resection for extra-articular ganglion cysts near popliteal vessels.

Effects of chlorantraniliprole on the development, fecundity and prey consumption of a non-specific predator, Rhynocoris fuscipes (Hemiptera: Reduviidae).

Transplant treatment with chlorantraniliprole (CAP) is a proactive approach to protect transplanted plants from pests during early establishment and has been comprehensively applied in tobacco fields in Guangdong Province, China. However, it is not known whether the high dose of CAP in transplant treatments has lethal or sublethal effects on the generalist predator Rhynocoris fuscipes Fabricius (Hemiptera: Reduviidae). To address this concern, the mortalities of R. fuscipes were assessed when 2nd instar larvae of R. fuscipes were in direct contact with or consuming CAP and when their eggs were exposed to CAP. Furthermore, 2nd instar nymphs R. fuscipes were long-term exposed to CAP until they reached adulthood, and their life table parameters were determined. After exposure to CAP, the activity of detoxification enzymes (P450, CaeE and GST) and the functional respond of R. fuscipes to their preys Agrotis ipsilon larvae were determined. In this study, CAP at all concentrations did not significantly increase the mortality of 2nd instar of R. fuscipes nymphs in comparison with the control. The detoxification enzyme (P450, CarE and GST) activities and the number of A. ipsilon larvae consumed by R. fuscipes in the transplant treatment were not affected by CAP after 3-d or long-term exposure. These results indicated that CAP was harmless to R. fuscipes according to IOBC protocols. However, during the treatment of 2nd instar nymphs with a label rate of 15 g AI/ha and a 5× label rate of 75 g AI/ha, CAP significantly prolonged the pre-adult and pre-oviposition periods, and treated adults had lower oviposition. Attention should be given to the time interval between transplant treatment and the release of this biocontrol agent into the field to minimize the impact of CAP on the predator R. fuscipes.

Reverse electron transfer: Novel anaerobic methanogenesis pathway regulated through exogenous CO2 synergized with biochar.

Acid accumulation and carbon emission are two major challenges in anaerobic digestion. Syntrophic consortia can employ reverse electron transfer (RET) to facilitate thermodynamically unfavorable redox reactions during acetogenesis. However, the potential mechanisms and regulatory methods of RET remain unclear. This study examines the regulatory mechanisms by which exogenous CO2 affects RET and demonstrates that biochar maximizes CO2 solubility at 25.8 mmol/L to enhance effects further. CO2 synergized with biochar significantly increases cumulative methane production and propionate degradation rate. From the bioenergetic perspective, CO2 decreases energy level to a maximum of -87 kJ/mol, strengthening the thermodynamic viability. The underlying mechanism can be attributed to RET promotion, as indicated by increased formate dehydrogenase and enrichment of H2/formate-producing bacteria with their partner Methanospirillum hungatei. Moreover, the 5 % 13CH4 and methane contribution result show that CO2 accomplishes directed methanogenesis. Overall, this investigation riches the roles of CO2 and biochar in AD surrounding RET.

Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures.

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Zero-valent iron enhanced methane production of anaerobic digestion by reinforcing microbial electron bifurcation coupled with direct inter-species electron transfer.

Zero-valent iron (ZVI) can facilitate methanogens of anaerobic digestion (AD). However, the impact of ZVI on the micro-energetic strategies of AD microorganisms remains uncertain. This study aimed to elucidate the development of an energy conservation model involving direct interspecies electron transfer (DIET) and electron bifurcate (EB) by using four types of ZVI. Overall, the ZVI addition resulted in a substantial increase in methane production (1.26 to 2.18 times higher), and the effect of boron (B) doped ZVI was particularly pronounced. The underlying mechanism may be the formation of energy harvest pathway related to DIET. In detail, B-doped ZVI could enhance its interfacial binding to cytochrome c. Decreased polar solvation energy from 20.473 to 1.509 kJ/mol is beneficial for electron transfer, thereby augmenting the flavin-bounded Cytc activity and DIET process. Besides, ZVI-enhanced EB enzyme activity like HdrA2B2C2-MvhAGD could improve the EB process, which can couple with DIET for electron transfer and energy conservation. Energy analysis based on EB-coupled DIET metabolism pathways demonstrated that the ATP saved in this coupled model theoretically line in 0.25 to 0.5 mol ATP/mol substrate. Overall, this study offers valuable insights into microbial energetic strategies pertaining to the utilization of conductive materials, with the target of enhancing methane recovery efficiency from organic waste.

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay.

Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

Deep Learning Imaging Reconstruction Algorithm for Carotid Dual Energy CT Angiography: Opportunistic Evaluation of Cervical Intervertebral Discs-A Preliminary Study.

Thus, the aim of this study is to evaluate the performance of deep learning imaging reconstruction (DLIR) algorithm in different image sets derived from carotid dual-energy computed tomography angiography (DECTA) for evaluating cervical intervertebral discs (IVDs) and compare them with those reconstructed using adaptive statistical iterative reconstruction-Veo (ASiR-V). Forty-two patients who underwent carotid DECTA were included in this retrospective analysis. Three types of image sets (70 keV, water-iodine, and water-calcium) were reconstructed using 50% ASiR-V and DLIR at medium and high levels (DLIR-M and DLIR-H). The diagnostic acceptability and conspicuity of IVDs were assessed using a 5-point scale. Hounsfield Units (HU) and water concentration (WC) values of the IVDs; standard deviation (SD); and coefficient of variation (CV) were calculated. Measurement parameters of the 50% ASIR-V, DLIR-M, and DLIR-H groups were compared. The DLIR-H group showed higher scores for diagnostic acceptability and conspicuity, as well as lower SD values for HU and WC than the ASiR-V and DLIR-M groups for the 70 keV and water-iodine image sets (all p < .001). However, there was no significant difference in scores and SD among the three groups for the water-calcium image set (all p > .005). The water-calcium image set showed better diagnostic accuracy for evaluating IVDs compared to the other image sets. The inter-rater agreement using ASiR-V, DLIR-M, and DLIR-H was good for the 70 keV image set, excellent for the water-iodine and water-calcium image sets. DLIR improved the visualization of IVDs in the 70 keV and water-iodine image sets. However, its improvement on color-coded water-calcium image set was limited.

Recognition memory deficits detected through eye-tracking in well-controlled children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Children with self-limited epilepsy characterized by centrotemporal spikes (SeLECTS) exhibit cognitive deficits in memory during the active phase, but there is currently a lack of studies and techniques to assess their memory development after well-controlled seizures. In this study, we employed eye-tracking techniques to investigate visual memory and its association with clinical factors and global intellectual ability, aiming to identify potential risk factors by examining encoding and recognition processes. METHODS: A total of 26 recruited patients diagnosed with SeLECTS who had been seizure-free for at least 2 years, along with 24 control subjects, underwent Wechsler cognitive assessment and an eye-movement-based memory task while video-electroencephalographic (EEG) data were recorded. Fixation and pupil data related to eye movements were utilized to detect distinct memory processes and subsequently to compare the cognitive performance of patients exhibiting different regression patterns on EEG. RESULTS: The findings revealed persistent impairments in visual memory among children with SeLECTS after being well controlled, primarily observed in the recognition stage rather than the encoding phase. Furthermore, the age at onset, frequency of seizures, and interictal epileptiform discharges exhibited significant correlations with eye movement data. SIGNIFICANCE: Children with SeLECTS exhibit persistent recognition memory impairment after being well controlled for the disease. Controlling the frequency of seizures and reducing prolonged epileptiform activity may improve memory cognitive development. The application of the eye-tracking technique may provide novel insights into exploring memory cognition as well as underlying mechanisms associated with pediatric epilepsy.

Pregnancy-related knowledge in women with epilepsy in childbearing age: A pilot questionnaire survey from China.

PURPOSE: We aim to understand the knowledge of and attitudes toward pregnancy issues among women with epilepsy (WWE) and their caregivers and analyze the answers from the questionnaire to expose topics that require educational activities; thus, WWE experiences pregnancy better. METHODS: WWE at their childbearing age and/or their caregivers who entered the Fourth Affiliated Hospital of Zhejiang University for treatment of their condition were invited to fill out a questionnaire between March 1 and November 31, 2022. RESULTS: A combined total of 205 WWE and 142 caregivers completed the questionnaires. Among the surveyed WWE, a majority (63.74%) reported experiencing at least one miscarriage or induced abortion. However, a significant proportion (84.62%) of these WWE were still able to successfully give birth to at least one child. Furthermore, the offspring of these WWE showed no significant differences compared to the offspring of women without epilepsy, as reported by 93.51% of the participants. The participants' knowledge regarding the impact of epilepsy on pregnancy was found to be comparable, with average scores of 7.74 and 7.84, respectively. The participants exhibited a limited comprehension of antiseizure medications (ASMs)-related knowledge, specifically pertaining to ASMs adjustment during pregnancy (17.56% vs. 16.90%) and offspring outcomes (30.24% vs. 26.06%). Statistical analysis revealed significant correlations between the overall score and education level (p < .001), as well as epilepsy duration (p = .008). Regarding the source of knowledge, participants acknowledged primarily relying on neurologists, who remained their preferred choice for consultation. CONCLUSION: In our study, the understanding of pregnancy-related knowledge did not differ from WWE and their caregivers, both are far from satisfactory in certain areas. It is urgent for WWE and their caregivers to improve their pregnancy-related knowledge of epilepsy. As their primary access is from knowledgeable health care professionals like neurologists, well-trained neurologists in epilepsy management during pregnancy are in need.