Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes.

BACKGROUND/OBJECTIVES: Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in "adiponectin paradox", we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation. METHODS: This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α. RESULTS: This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036-0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03-0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5-49.2, P = 0.02). CONCLUSIONS: In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.

Utilization of the Shensheng-Piwen changed medicinal powder extracts combines metal-organic frameworks as an antibacterial agent.

Introduction: Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs. Methods: This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts. Results: Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against S. aureus, with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of S. aureus revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of S. aureus. Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect. Discussion: In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against S. aureus infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Yield-related quantitative trait loci identification and lint percentage hereditary dissection under salt stress in upland cotton.

Salinity is frequently mentioned as a major constraint in worldwide agricultural production. Lint percentage (LP) is a crucial yield-component in cotton lint production. While the genetic factors affect cotton yield in saline soils are still unclear. Here, we employed a recombinant inbred line population in upland cotton (Gossypium hirsutum L.) and investigated the effects of salt stress on five yield and yield component traits, including seed cotton yield per plant, lint yield per plant, boll number per plant, boll weight, and LP. Between three datasets of salt stress (E1), normal growth (E2), and the difference values dataset of salt stress and normal conditions (D-value), 87, 82, and 55 quantitative trait loci (QTL) were detectable, respectively. In total, five QTL (qLY-Chr6-2, qBNP-Chr4-1, qBNP-Chr12-1, qBNP-Chr15-5, qLP-Chr19-2) detected in both in E1 and D-value were salt related QTL, and three stable QTL (qLP-Chr5-3, qLP-Chr13-1, qBW-Chr5-5) were detected both in E1 and E2 across 3 years. Silencing of nine genes within a stable QTL (qLP-Chr5-3) highly expressed in fiber developmental stages increased LP and decreased fiber length (FL), indicating that multiple minor-effect genes clustered on Chromosome 5 regulate LP and FL. Additionally, the difference in LP caused by Gh_A05G3226 is mainly in transcription level rather than in the sequence difference. Moreover, silencing of salt related gene (GhDAAT) within qBNP-Chr4-1 decreased salt tolerance in cotton. Our findings shed light on the regulatory mechanisms underlining cotton salt tolerance and fiber initiation.

MRPS9-Mediated Regulation of the PI3K/Akt/mTOR Pathway Inhibits Neuron Apoptosis and Protects Ischemic Stroke.

Neuronal apoptosis is crucial in the pathophysiology of ischemic stroke (IS), albeit its underly24ing mechanism remaining elusive. Investigating the mechanism of neuronal apoptosis in the context of IS holds substantial clinical value for enhancing the prognosis of IS patients. Notably, the MRPS9 gene plays a pivotal role in regulating mitochondrial function and maintaining structural integrity. Utilizing bioinformatic tactics and the extant gene expression data related to IS, we conducted differential analysis and weighted correlation network analysis (WGCNA) to select important modules. Subsequent gene interaction analysis via the STRING website facilitated the identification of the key gene-mitochondrial ribosomal protein S9 (MRPS9)-that affects the progression of IS. Moreover, possible downstream signaling pathways, namely PI3K/Akt/mTOR, were elucidated via Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) pathway analysis. Experimental models were established utilizing oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. Changes in gene and protein expression, as well as cell proliferation and apoptosis, were monitored through qPCR, WB, CCK8, and flow cytometry. An OGD/R cell model was further employed to investigate the role of MRPS9 in IS post transfusion of MRPS9 overexpression plasmids into cells. Further studies were conducted by transfecting overexpressed cells with PI3K/Akt/mTOR signaling pathway inhibitor LY294002 to unveil the mechanism of MRPS9 in IS. Bioinformatic analysis revealed a significant underexpression of MRPS9 in ischemic stroke patients. Correspondingly, in vitro experiments with HN cells subjected to OGD/R treatment demonstrated a marked reduction in MRPS9 expression, accompanied by a decline in cell viability, and an increase cell apoptosis. Notably, the overexpression of MRPS9 mitigated the OGD/R-induced decrease in cell viability and augmentation of apoptosis. In animal models, MRPS9 expression was significantly lower in the MCAO/R group compared to the sham surgery group. Further, the KEGG pathway analysis associated MRPS9 expression with the PI3K/Akt/mTOR signaling pathway. In cells treated with the specific PI3K/Akt/mTOR inhibitor LY294002, phosphorylation levels of Akt and mTOR were decreased, cell viability decreased, and apoptosis increased compared to the MRPS9 overexpression group. These findings collectively indicate that MRPS9 overexpression inhibits PI3K/Akt/mTOR pathway activation, thereby protecting neurons from apoptosis and impeding IS progression. However, the PI3K/Akt/mTOR inhibitor LY294002 is capable of counteracting the protective effect of MRPS9 overexpression on neuronal apoptosis and IS. Our observations underscore the potential protective role of MRPS9 in modulating neuronal apoptosis and in attenuating the pathophysiological developments associated with IS. This is achieved through the regulation of the PI3K/Akt/mTOR pathway. These insights forge new perspectives and propose novel targets for the strategic diagnosis and treatment of IS.

Synergistically Coupling Atomic-Level Defect-Manipulation and Nanoscopic-Level Interfacial Engineering Enables Fast and Durable Sodium Storage.

Through inducing interlayer anionic ligands and functionally modifying conductive carbon-skeleton on the transition metal chalcogenides (TMCs) parent to achieve atomic-level defect-manipulation and nanoscopic-level architecture design is of great significance, which can broaden interlayer distance, optimize electronic structure, and mitigate structural deformation to endow high-efficiency battery performance of TMCs. Herein, an intriguing 3D biconcave hollow-tyre-like anode constituted by carbon-packaged defective-rich SnSSe nanosheet grafting onto Aspergillus niger spores-derived hollow-carbon (ANDC@SnSSe@C) is reported. Systematically experimental investigations and theoretical analyses forcefully demonstrate the existence of anion Se ligand and outer-carbon all-around encapsulation on the ANDC@SnSSe@C can effectively yield abundant structural defects and Na+ -reactivity sites, accelerate rapid ion migration, widen interlayer spacing, as well as relieve volume expansion, thus further resolving the critical issues throughout the charge-discharge processes. As anticipated, as-fabricated ANDC@SnSSe@C anode contributes extraordinary reversible capacity, wonderful cyclic lifespan with 83.4% capacity retention over 2000 cycles at 20.0 A g-1 , and exceptional rate capability. A series of correlated kinetic investigations and ex situ characterizations deeply reveal the underlying springheads for the ion-transport kinetics, as well as synthetically elucidate phase-transformation mechanism of the ANDC@SnSSe@C. Furthermore, the ANDC@SnSSe@C-based sodium ion full cell and hybrid capacitor offer high-capacity contribution and remarkable energy-density output, indicative of its great practicability.

Hierarchical Architecture Engineering of Branch-Leaf-Shaped Cobalt Phosphosulfide Quantum Dots: Enabling Multi-Dimensional Ion-Transport Channels for High-Efficiency Sodium Storage.

New-fashioned electrode hosts for sodium-ion batteries (SIBs) are elaborately engineered to involve multifunctional active components that can synergistically conquer the critical issues of severe volume deformation and sluggish reaction kinetics of electrodes toward immensely enhanced battery performance. Herein, it is first reported that single-phase CoPS, a new metal phosphosulfide for SIBs, in the form of quantum dots, is successfully introduced into a leaf-shaped conductive carbon nanosheet, which can be further in situ anchored on a 3D interconnected branch-like N-doped carbon nanofiber (N-CNF) to construct a hierarchical branch-leaf-shaped CoPS@C@N-CNF architecture. Both double carbon decorations and ultrafine crystal of the CoPS in-this exquisite architecture hold many significant superiorities, such as favorable train-relaxation, fast interfacial ion-migration, multi-directional migration pathways, and sufficiently exposed Na+ -storage sites. In consequence, the CoPS@C@N-CNF affords remarkable long-cycle durability over 10 000 cycles at 20.0 A g-1 and superior rate capability. Meanwhile, the CoPS@C@N-CNF-based sodium-ion full cell renders the potential proof-of-feasibility for practical applications in consideration of its high durability over a long-term cyclic lifespan with remarkable reversible capacity. Moreover, the phase transformation mechanism of the CoPS@C@N-CNF and fundamental springhead of the enhanced performance are disclosed by in situ X-ray diffraction, ex situ high-resolution TEM, and theoretical calculations.

Bio-inspired Ti3C2Tx MXene composite coating for enhancing corrosion resistance of aluminum alloy in acidic environments.

Aluminum alloy (Al alloy) suffers from severe corrosion in acidic solution. Two-dimensional (2D) MXene-based composite coatings show great prospects for corrosion protection on metals used in special conditions. The composite coatings still face challenges in complex functionalization and orientation control. In harsh conditions, the long-term ability and roles of MXene in corrosion protection are still not clear. Here, a bio-inspired myristic-calcium chloride-Ti3C2Tx MXene (MA + CaCl2 + MXene) composite coating is successfully prepared on aluminum alloy (Al alloy) by electrodeposition process. Electrochemical tests, surface morphology, and chemical composition are analyzed to investigate the corrosion resistance and protection mechanism of the MXene coating in acidic solution (0.5 M H2SO4 + 2 ppm HF). As a result, the incorporation of MXene can significantly reduce corrosion current density (7.498 × 10-8 A/cm2) by âˆ¼ 5 orders of magnitude and impedance modulus at 0.01 Hz (|Z|0.01 Hz) value of the composite coating is 196.8 Ω·cm2, which is over 4 times higher than that of bare Al alloy (40.74 Ω·cm2) after immersion test for 72 h. Furthermore, the in-situ corrosion test confirms the enhanced corrosion resistance of the MA + CaCl2 + MXene composite coating. The MXene can increase coating thickness to 23.6 ± 0.4 µm, reduce porosity to (5.845 ± 1) × 10-5, decrease the diffusion coefficients of H+ to (1.587 ± 0.3) × 10-9 cm2/s, and enhance the adhesion of the coating to the substrate (the delamination time exceeds 5 h), thus providing improved anti-corrosion ability. This strategy opens up new prospects for construction of 2D MXene-based anti-corrosion coatings.

[Effect of Twin-block in adolescents with mandibular retrusion and normal anterior overjet].

PURPOSE: To investigate the therapeutic effect of modified fixed Twin-block on patients whose mandible was retruded and anterior overjet was normal. METHODS: Thirty-six adolescents with mandibular retrusion and normal anterior overjet were selected. The goal of occlusal reconstruction was to move the soft tissue pogonion forward to the zero meridian(0°). Fixed Twin-block combined with the mini-implants on the mandibular buccal shelf was used to promote mandibular growth. After 12 months, the appliances were removed step by step to observe the stability of the jaw relationship. Fixed orthodontic treatment was performed to achieve ideal occlusion and coordinated profile. SPSS 13.0 software package was used for Student's t test. RESULTS: The length of mandibular body increased significantly which facilitated the forward movement of the soft tissue pogonion, and the profile changed from convex to straight. Comparison of the results before and after Twin-block treatment showed that Co-Gn, SNB, U1-SN, U6-0°, U1-0°, U1-L1, anterior overbite, anterior overjet, Pog's-0°, L1-0° and lower anterior facial height changed significantly (P＜0.05). Comparison of the results before and after fixed orthodontic treatment showed that PP-MP, SN-MP, U6-0°, IMPA, L1-0°,U1-SN, U1-L1, anterior overbite and overjet changed significantly(P＜0.05). CONCLUSIONS: Modified fixed Twin-block combined with mini-implants on the mandibular buccal shelf can effectively stimulate the mandibular growth and improve the lateral profile of patients with mandibular retrusion and normal overjet.

The Role of TGF-ß during Pregnancy and Pregnancy Complications.

Transforming growth factor beta (TGF-ß), a multifunctional cytokine, is one of the most important inflammatory cytokines closely related to pregnancy. It plays significant roles in hormone secretion, placental development, and embryonic growth during pregnancy. TGF-ß is implicated in embryo implantation and inhibits the invasion of extraepithelial trophoblast cells. It also moderates the mother-fetus interaction by adjusting the secretion pattern of immunomodulatory factors in the placenta, consequently influencing the mother's immune cells. The TGF-ß family regulates the development of the nervous, respiratory, and cardiovascular systems by regulating gene expression. Furthermore, TGF-ß has been associated with various pregnancy complications. An increase in TGF-ß levels can induce the occurrences of pre-eclampsia and gestational diabetes mellitus, while a decrease can lead to recurrent miscarriage due to the interference of the immune tolerance environment. This review focuses on the role of TGF-ß in embryo implantation and development, providing new insights for the clinical prevention and treatment of pregnancy complications.

Construction of an Efficient Genetic Transformation System for Watercress (Nasturtium officinale W. T. Aiton).

Based on the established efficient regeneration system for watercress in our laboratory, we optimized the processes of pretreatment, co-culture, and differentiation culture. Through GFP fluorescence and PCR identification, we successfully obtained transgenic watercress with the DR5 gene, which allowed us to investigate the distribution details of auxin in the growth process of watercress. Our findings provide an effective method for gene function research and lay the foundation for innovative utilization of germplasm resources of watercress.

Leveraging a disulfidptosis/ferroptosis-based signature to predict the prognosis of lung adenocarcinoma.

BACKGROUND: Disulfidptosis and Ferroptosis are two novel forms of cell death. Although their mechanisms differ, research has shown that there is a relationship between the two. Investigating the connection between these two forms of cell death can further deepen our understanding of the development and progression of cancer, and provide better prediction models for accurate prognosis. METHODS: In this study, RNA sequencing (RNA-seq) data, clinical data, single nucleotide polymorphism (SNP) data, and single-cell sequencing data were obtained from public databases. We used weighted gene co-expression network analysis (WGCNA) and unsupervised clustering to identify new Disulfidptosis/Ferroptosis-Related Genes (DFRG), and constructed a LASSO COX prognosis model that was externally validated. To further explore this novel signature, pathway and function analysis was performed, and differences in gene mutation frequency between high- and low-risk groups were studied. Importantly, we also conducted research on immune checkpoint, immune cell infiltration levels and immune resistance indicators, in addition to analyzing real clinical immunotherapy data. RESULTS: We have identified four optimal disulfidptosis/ferroptosis-related genes (ODFRGs) that are differentially expressed and associated with the prognosis of Lung Adenocarcinoma (LUAD). These genes include GMPR, MCFD2, MRPL13, and SALL2. Based on these ODFRGs, we constructed a robust prognostic model in this study, and the high-risk group showed significantly lower overall survival (OS) compared to the low-risk group. Furthermore, this model can also predict the immunotherapy outcomes of LUAD patients to some extent.

Aspirin protects human trophoblast HTR-8/SVneo cells from H2O2-Induced oxidative stress via NADPH/ROS pathway.

INTRODUCTION: Pre-eclampsia (PE) is a pregnancy complication that can lead to maternal, fetal, and neonatal deaths in clinical practice. Accumulation of trophoblastic reactive oxygen species (ROS), which could result in oxidative stress and cell apoptosis, is considered to play an important role in PE pathology. It has been reported that aspirin has a positive effect on PE treatment in high-risk pregnant women. METHODS: In vitro, extravillous trophoblast cell line (HTR-8/SVneo) were treated with hydrogen peroxide (H2O2, 150 µM) after the presence of aspirin (90 and 120 µM) with or without GKT137831 (a Nox4 inhibitor, 20 µM). A series of experiments including CCK-8 assays, flow cytometry, biochemical testing, and Western Blotting etc. verified the protective effects and potential mechanisms of aspirin against oxidative stress-induced damage in PE. RESULTS: Our results demonstrated that H2O2 induces oxidative stress and apoptosis in HTR8/SVneo cells. However, aspirin pretreatment rescue cell viability and reduce LDH activity of HTR-8/SVneo cells. Aspirin can suppress the ROS overproduction and MDA level while increase SOD content and CAT activity. In addition, aspirin pretreatment significantly alleviated cell apoptosis and suppressed the expression of Nox4 and its subunits (p22phox and p47phox) at protein and mRNA levels. The above results were more obvious after the combination of aspirin with GKT137831. DISCUSSION: This study demonstrated that aspirin protects human trophoblasts against H2O2-induced oxidative stress and cell apoptosis via suppressing NADPH/ROS pathway. These findings provide novel insights for the application of aspirin as a protective and curative agent against PE.

The Developmental Mechanism of the Root System of Cultivated Terrestrial Watercress.

A well-developed root system is crucial for the rapid growth, asexual reproduction, and adaptation to the drought environments of the watercress. After analyzing the transcriptome of the watercress root system, we found that a high concentration of auxin is key to its adaptation to dry conditions. For the first time, we obtained DR5::EGFP watercress, which revealed the dynamic distribution of auxin in watercress root development under drought conditions. Via the application of naphthylphthalamic acid (NPA), 4-biphenylboronic acid (BBO), ethylene (ETH), abscisic acid (ABA), and other factors, we confirmed that auxin has a significant impact on the root development of watercress. Finally, we verified the role of auxin in root development using 35S::NoYUC8 watercress and showed that the synthesis of auxin in the root system mainly depends on the tryptophan, phenylalanine, and tyrosine amino acids (TAA) synthesis pathway. After the level of auxin increases, the root system of the watercress develops toward adaptation to dry environments. The formation of root aerenchyma disrupts the concentration gradient of auxin and is a key factor in the differentiation of lateral root primordia and H cells in watercress.

Idiopathic Isolated Adrenocorticotropic Hormone Deficiency: A Single-Center Retrospective Study.

Idiopathic isolated adrenocorticotrophic hormone deficiency (IIAD) is rare, with high clinical omission and misdiagnosis rates. This study retrospectively collected information on clinical presentation, laboratory findings, and treatment response of 17 patients with IIAD at Jining No. 1 People's Hospital from January 2014 to December 2022. The clinical characteristics were summarized, and the pertinent data were analyzed. As a result, most of the patients with IIAD were male (94.12%), with age at onset ranging from 13 to 80 years. The primary manifestations were anorexia (88.24%), nausea (70.59%), vomiting (47.06%), fatigue (64.71%), and neurological or psychiatric symptoms (88.24%). The median time to diagnosis was 2 months and the longest was 10 years. Laboratory tests mostly showed hyponatremia (88.24%) and hypoglycemia (70.59%). The symptoms and laboratory indicators returned to normal after supplementing patients with glucocorticoids. IIAD has an insidious onset and atypical symptoms; it was often misdiagnosed as gastrointestinal, neurological, or psychiatric disease. The aim of this study was to improve clinicians' understanding of IIAD, patients with unexplained gastrointestinal symptoms, neurological and psychiatric symptoms, hyponatremia, or hypoglycemia should be evaluated for IIAD and ensure early diagnosis and treatment.

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma.

Background: Cuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients. Methods: RNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB). Results: We have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.

Energy Harvesting System Whose Potential Is Mapped with the Modified Fibonacci Function.

In this paper, we compare three energy harvesting systems in which we introduce additional bumpers whose mathematical model is mapped with a non-linear characteristic based on the hyperbolic sine Fibonacci function. For the analysis, we construct non-linear two-well, three-well and four-well systems with a cantilever beam and permanent magnets. In order to compare the effectiveness of the systems, we assume comparable distances between local minima of external wells and the maximum heights of potential barriers. Based on the derived dimensionless models of the systems, we perform simulations of non-linear dynamics in a wide spectrum of frequencies to search for chaotic and periodic motion zones of the systems. We present the issue of the occurrence of transient chaos in the analyzed systems. In the second part of this work, we determine and compare the effectiveness of the tested structures depending on the characteristics of the bumpers and an external excitation whose dynamics are described by the harmonic function, and find the best solutions from the point view of energy harvesting. The most effective impact of the use of bumpers can be observed when dealing with systems described by potential with deep external wells. In addition, the use of the Fibonacci hyperbolic sine is a simple and effective numerical tool for mapping non-linear properties of such motion limiters in energy harvesting systems.

Cuproptosis/ferroptosis-related gene signature is correlated with immune infiltration and predict the prognosis for patients with breast cancer.

Background: Breast invasive carcinoma (BRCA) is a malignant tumor with high morbidity and mortality, and the prognosis is still unsatisfactory. Both ferroptosis and cuproptosis are apoptosis-independent cell deaths caused by the imbalance of corresponding metal components in cells and can affect the proliferation rate of cancer cells. The aim in this study was to develop a prognostic model of cuproptosis/ferroptosis-related genes (CFRGs) to predict survival in BRCA patients. Methods: Transcriptomic and clinical data for breast cancer patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cuproptosis and ferroptosis scores were determined for the BRCA samples from the TCGA cohort using Gene Set Variation Analysis (GSVA), followed by weighted gene coexpression network analysis (WGCNA) to screen out the CFRGs. The intersection of the differentially expressed genes grouped by high and low was determined using X-tile. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) were used in the TGCA cohort to identify the CFRG-related signature. In addition, the relationship between risk scores and immune infiltration levels was investigated using various algorithms, and model genes were analyzed in terms of single-cell sequencing. Finally, the expression of the signature genes was validated with quantitative real-time PCR (qRT‒PCR) and immunohistochemistry (IHC). Results: A total of 5 CFRGs (ANKRD52, HOXC10, KNOP1, SGPP1, TRIM45) were identified and were used to construct proportional hazards regression models. The high-risk groups in the training and validation sets had significantly worse survival rates. Tumor mutational burden (TMB) was positively correlated with the risk score. Conversely, Tumor Immune Dysfunction and Exclusion (TIDE) and tumor purity were inversely associated with risk scores. In addition, the infiltration degree of antitumor immune cells and the expression of immune checkpoints were lower in the high-risk group. In addition, risk scores and mTOR, Hif-1, ErbB, MAPK, PI3K/AKT, TGF-ß and other pathway signals were correlated with progression. Conclusion: We can accurately predict the survival of patients through the constructed CFRG-related prognostic model. In addition, we can also predict patient immunotherapy and immune cell infiltration.

[Genetic modification of acetogens and optimization of fermentation process in C1-gas bioconversion].

The current linear economy model relies on fossil energy and increases CO2 emissions, which contributes to global warming and environmental pollution. Therefore, there is an urgent need to develop and deploy technologies for carbon capture and utilization to establish a circular economy. The use of acetogens for C1-gas (CO and CO2) conversion is a promising technology due to high metabolic flexibility, product selectivity, and diversity of the products including chemicals and fuels. This review focuses on the physiological and metabolic mechanisms, genetic and metabolic engineering modifications, fermentation process optimization, and carbon atom economy in the process of C1-gas conversion by acetogens, with the aim to facilitate the industrial scale-up and carbon negative production through acetogen gas fermentation.

Nuclear PLD1 combined with NPM1 induces gemcitabine resistance through tumorigenic IL7R in pancreatic adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%. Of PDAC patients, 15%-20% are eligible for radical surgery. Gemcitabine is an important chemotherapeutic agent for patients with PDAC; however, the efficacy of gemcitabine is limited due to resistance. Therefore, reducing gemcitabine resistance is essential for improving survival of patients with PDAC. Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC. METHODS: We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment. Then, co-IP, ChIP, ChIP-seq, transcriptome sequencing, and qPCR were used to determine the specific mechanism by which phospholipase D1 (PLD1) confers resistance to gemcitabine. RESULTS: PLD1 combines with nucleophosmin 1 (NPM1) and triggers NPM1 nuclear translocation, where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor (IL7R) expression. Upon interleukin 7 (IL-7) binding, IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein, BCL-2, and induce gemcitabine resistance. The PLD1 inhibitor, Vu0155069, targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells. CONCLUSIONS: PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1, further promoting the downstream JAK1/STAT5/Bcl-2 pathway. Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.