Reverse Reaction Research Articles

Pre-intercalated Sodium Ions Enhance Sodium Storage of MoS2 Anode by Mitigating Structural Dissociation.

Molybdenum disulfide (MoS2) is a promising anode for sodium-ion batteries (SIBs) due to its high theoretical capacity and layered structure. However, a poor reversible conversion reaction and a low initial Coulombic efficiency (ICE) limit its practical application. This study systematically investigated the potential of pre-intercalated sodium ions molybdenum disulfide (Na-MoS2) as an anode material for SIBs. Because of the mitigation of MoS2 structural dissociation and effective replenishment of active sodium ions, Na-MoS2 delivered an outstanding capacity of 507.7 mAh g-1 after 2000 cycles at 5 A g-1, along with an ICE of 95.30%. Pre-intercalating sodium ions can expand interlayer spacing and modulate electronic structure, allowing Na-MoS2 to have greater tolerance to the electrochemical intercalation/extraction process. Furthermore, the conversion reaction of Na-MoS2 has a higher Gibbs free energy, implying its structural dissociation is thermodynamically unfavorable. This work provides a new perspective on the study of transition metal dichalcogenide electrode materials for SIBs.

Autophagy Attenuates Oxidative Stress-Induced Collagen Degradation in Vaginal Fibroblasts: Implications for Pelvic Organ Prolapse.

The relationship between autophagy and pelvic organ prolapse (POP) remains unknown. The aim of this novel experimental study, utilizing tissue samples derived from women undergoing gynecological surgery, is to investigate the role of autophagy in mitigating collagen degradation in human vaginal fibroblasts induced by oxidative stress, with particular emphasis on its implications in the pathogenesis of POP. Exploring the role of autophagy in protecting against collagen degradation and cellular senescence in human vaginal fibroblasts under oxidative stress may offer new insights into therapeutic strategies for conditions such as POP. This study consists of laboratory-based experimental research that utilizes tissue samples collected from female patients undergoing gynecological surgery to analyze the role of autophagy in collagen degradation induced by oxidative stress. By treating with different concentrations of hydrogen peroxide (H2O2) and using rapamycin (RAPA) and 3-methyladenine (3-MA) as autophagy activators and inhibitors respectively, the effects on human vaginal fibroblasts (HVFs) were evaluated. Cell viability was determined using the Cell Counting Kit-8 test. Cellular senescence was determined with senescence-associated-β-galactosidase labeling and western blotting to identify the expression of p21 and p53. Reactive oxygen species (ROS) were determined with 2,7-dichlorofluorescin diacetate. Additionally, western blotting was used to establish collagen I, collagen III, microtubule-associated protein 1A/1B-light chain 3 (LC3), Beclin-1, and p62 and reverse transcription-quantitative polymerase chain reaction was used to determine the mRNA levels of COL3A1, COL1A1,TIMP1,MMP9,LC3,andBeclin-1to investigate collagen metabolism and autophagic activity. The results showed that high-dose H2O2 significantly increased ROS levels, cell senescence, and collagen degradation in HVFs. The combined use of RAPA significantly reduced ROS levels, collagen degradation, and cell senescence, but this protective effect disappeared when 3-MA was added. Nevertheless, co-treatment of HVFs with RAPA, H2O2, and 3-MA abolished the positive impact of RAPA via boosting autophagy resistance. Autophagy inhibits collagen degeneration and cellular senescence caused by oxidative stress.

Brassinin from Brassica campestris L. inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis.

Indole phytoalexins, plant-derived compounds present in cruciferous vegetables, have demonstrated anticancer properties. Brassinin (BSN), derived from Brassica campestris L. var. campestris, is known for its potent antitumor effects on various cancers. However, the role of ferroptosis in regulating the antitumor effects of BSN has not been fully elucidated. The components of B. campestris L. against colorectal cancer (CRC) were analyzed by network pharmacology. CCK-8 assay and colony formation assay detected cell viability induced by BSN. Molecular docking verified the binding of BSN to the target protein. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed whether BSN can inactivate the NRF2 signaling and inhibit the expression of p62 and HO-1. The RKO-xenograft tumor models were established and then were treated by 75 or 150 mg/kg BSN to verify the antitumor efficacy and side effects of BSN. Network pharmacology suggested that BSN is the most important component of B. campestris L. against CRC. BSN inhibits CRC cell viability in a dose- and time-dependent manner. Furthermore, this inhibitory effect is associated with the induction of ferroptosis, as BSN suppresses the cell viability of CRC by inducing GPX4-regulated ferroptosis. BSN may bind to NRF2 protein to inactivate the NRF2 signaling, inhibiting the expression of p62 and HO-1. Importantly, a low dose or a high dose of BSN significantly reduced the tumor growth invivo. Our findings reveal that BSN blocks CRC growth by inducing p62/NRF2/GPX4-regulated ferroptosis, which may be a novel lead compound for tumor treatment.

Unraveling Redox Mediator-Assisted Chemical Relithiation Mechanism for Direct Recycling of Spent Ni-Rich Layered Cathode Materials.

The increasing demand for Li-ion batteries across various energy storage applications underscores the urgent need for environmentally friendly and efficient direct recycling strategies to address the issue of substantial cathode waste. Diverse reducing agents for Li supplements, such as quinone molecules, have been considered to homogenize the Li distribution in the cathode materials obtained after cycling; however, the detailed reaction mechanism is still unknown. Herein, the ideal electrochemical potential factor and reaction mechanism of the redox mediator 3,5-di-tert-butyl-o-benzoquinone (DTBQ) for the chemical relithiation of high-Ni-layered cathodes are elucidated. Here, 100% efficiency of DTBQ-assisted chemical relithiation is achieved by adjusting the direct immersion time of Li-deficient cathode electrodes. The reversible reaction features of the physical and chemical structures of both the regenerated cathodes and the DTBQ molecules are investigated using advanced characterization and density functional theory calculations. These findings emphasize the potential of redox-mediator-assisted chemical relithiation for realizing direct recycling processes and offer a facile and sustainable solution for battery recycling.

Analyses of Adverse Drug Reactions to Fluoroquinolones in Spontaneous Reports Before and After the Referral and in Clinical Routine Cases.

In November 2018, the European Medicines Agency (EMA) restricted the use of fluoroquinolones (used by mouth, injections or inhalation) in the context of a referral due to long-lasting and potentially irreversible adverse drug reactions (ADRs). Fluoroquinolones should no longer be used to treat mild or moderate bacterial infections unless other antibacterials cannot be used. The first aim of our study was to analyze whether in the period before compared with after the referral the characteristics of spontaneous ADR reports related to fluoroquinolones differed and whether specific ADRs were more frequently reported for fluoroquinolones compared with cotrimoxazole. Secondly, we analyzed whether the ADR profile differed between individual fluoroquinolones. Finally, the number of fluoroquinolone reports was considered in relation to the number of outpatient drug prescriptions. All spontaneous ADR reports from Germany received before the referral (01/2014-12/2019) and after the referral (01/2020-12/2022) for adults in which fluoroquinolones (n=2575; n=967) or cotrimoxazole (n=299, n=275) were reported as suspected/interacting were identified in the European ADR database, EudraVigilance. The ADR reports were descriptively analyzed concerning the reported characteristics. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression analyses, which were performed to investigate whether aortic aneurysms, retinal detachments, cardiac arrhythmias, peripheral polyneuropathies, nervous system disorders, toxic liver diseases and non-traumatic injuries of muscles, tendons and synovialis were more frequently reported for fluoroquinolones compared with cotrimoxazole. Stratified analyses between fluoroquinolones were conducted by calculating ORs and their 95% CIs by using two-by-two tables. Reporting rates were calculated by dividing the number of fluoroquinolone reports by the number of fluoroquinolone prescriptions. Reporting rates of fluoroquinolones clearly increased until 2019 and decreased afterward. Only minor differences in the characteristics of fluoroquinolone reports (e.g., regarding the indications) were observed in reports received before and after the referral. In both periods, peripheral neuropathies, nervous system, and muscle and tendon disorders were more often reported for fluoroquinolones than cotrimoxazole. In the pooled fluoroquinolone-stratified analyses, (i) peripheral neuropathies and nervous system disorders were more frequently reported for ciprofloxacin, (ii) non-traumatic injuries of muscle, tendon, and synovialis were more often reported for levofloxacin, and (iii) cardiac arrhythmias and toxic liver diseases were more frequently reported for moxifloxacin compared with the other fluoroquinolones. In accordance with a reminder sent by the EMA referring to prescribing trends for fluoroquinolones, our study showed that the characteristics of spontaneous ADR reports for fluoroquinolones after the referral were similar to those before the referral, underlining the importance of adhering to the recommended restrictions issued by the EMA. In addition, we observed individual differences between ciprofloxacin, levofloxacin, and moxifloxacin with regard to their ADR profile. Further studies are needed to confirm our results.

Upregulating lncRNA GUSBP11 protects chondrocytes from IL-1β-induced inflammatory damage via inhibiting miR-122-5p.

Studies have demonstrated that several lncRNAs exhibit abnormal expression levels in patients suffering from osteoarthritis, and in-depth investigation of these aberrantly expressed lncRNAs may pave the way for innovative therapeutic strategies targeting OA. The aim of this study was to examine the expression of glucuronidase beta pseudogene 11 (GUSBP11) in OA patients and to elucidate its potential molecular mechanism. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect GUSBP11 levels on cartilage tissues and serum samples obtained from OA patients. To establish an in vitro OA cell model, interleukin-1β (IL-1β) was utilized to induce CHON-001 and ATDC5 cell lines. Cell counting kit-8 (CCK-8) assay and flow cytometry were performed to evaluate cell viability and apoptosis, and enzyme-linked immunosorbent assay (ELISA) was employed to qualify the levels of inflammatory factors. StarBase database predicted that miR-122-5p was the target gene of GUSBP11. Subsequently, luciferase reporter genes were conducted to validate this interaction. Potential target genes of miR-122-5p were predicted, followed by gene function annotation and correlation analysis of these targets. Our findings revealed that GUSBP11 expression was markedly decreased in both the cartilage tissues and serum of OA patients. Diminished levels of GUSBP11 showed high diagnostic accuracy for OA. In the IL-1β-induced OA cell model, GUSBP11 expression was notably reduced, leading to decreased cell viability, an increase in apoptotic cells, and elevated levels of inflammatory factors. Up-regulation of GUSBP11 significantly ameliorated these adverse effects. Luciferase reporter genes confirmed the interaction between GUSBP11 and miR-122-5p, indicating that an increase in miR-122-5p drastically inhibited cell viability while promoting apoptosis and inflammation. In conclusion, within the context of the in vitro OA cell model, GUSBP11 appears to exacerbate IL-1β-induced chondrocyte inflammation through the up-regulation of miR-122-5p. This underscores the potential of GUSBP11 as a novel target and avenue for therapeutic intervention in the treatment of OA.

M6A-modified lncRNA GAS5 promotes M1-polarization of microglia in alcohol use disorder.

Long noncoding RNA (lncRNA) are essential for modulating the onset and progression of alcohol use disorder (AUD). In this study, we investigated the molecular pathways through which lncRNA may contribute to AUD development. We assessed the expression levels of long noncoding RNA GAS5 (lncRNA GAS5) and microRNA-136-5p (miR-136-5p) in AUD tissue samples and cell lines using reverse transcription-quantitative polymerase chain reaction. Detection of GAS5 N6-methyladenosine (m6A) modifications, facilitated by alkylation repair homolog 5 (ALKBH5), was performed using RNA immunoprecipitation and RNA pull-down assays. The effect of GAS5 on the functionality of SH-SY5Y cells was evaluated using CCK-8 and Transwell assays. Our findings showed high levels of GAS5 expression in both AUD tissues and cell lines. Overexpression of GAS5 decreased the migratory capability of SH-SY5Y cells, whereas silencing GAS5 increased this ability. Bioinformatics analyses predicted a relationship between expression levels of miR-136-5p and GAS5, which was subsequently confirmed using dual-luciferase reporter assays. Additionally, we discovered that GAS5 acts as a sponge for miR-136-5p, leading to the upregulation of ATF2. Elevated levels of ATF2 are associated with M1 microglial polarization. In summary, m6A-modified GAS5 may influence the M1 polarization of microglia via the miR-136-5p/ATF2 pathway. Statistical evaluations were performed using GraphPad Prism V8.0, employing the student's t-test for comparisons between two groups, assuming a normal distribution and equal variances. When variances were unequal, but normality was maintained, the corrected Student's t-test was applied. The non-parametric Wilcoxon rank-sum test was used to analyze non-normally distributed data, and one-way ANOVA was used to compare three or more groups. Independent replication was ensured in the studies, with each experiment repeated at least three times and statistical significance was set at P < 0.05.

Role of miRNAs in Regulating Ascending Aortic Dilation in Bicuspid Aortic Valve Patients Operated for Aortic Stenosis.

Deregulation of micro-RNAs (miRNAs) may contribute to mechanisms of injury in the bicuspid aortic valve (BAV). Our objective was to investigate the expression of miRNAs in aortic tissue from patients who underwent aortic valve replacement for aortic stenosis and its relationship with aortic dilatation. The study included 78 patients, 40 with bicuspid aortic valve (BAV) and 38 with tricuspid aortic valve (TAV). The expression of miRNA-17-5p, hsa-let-7e, and miRNA-196a-5p in human aortic tissue was evaluated by a reverse transcriptase polymerase chain reaction (RT-qPCR). Comparative analysis between patients with BAV and controls with TAV explored the association between the miRNAs and aortic dilatation (AD), calcification, valve dysfunction, and stenosis. The results showed that the expression levels of miRNA-Let-7e-5p and miRNA-196-5p were mostly increased in patients with BAV and aortic dilatation (p = 0.01 and p = 0.01), respectively. In contrast, the levels of miRNA-17a-5p (p < 0.20) were lower but without a statistically significant difference. The downregulation of miRNA-17a-5p and the upregulation of miR-Let-7e-5p and miR-196-5p were related to an increased risk of AD risk. Subjects with BAVs with or without double aortic lesions had higher expression levels of Let-7e-5p and miRNA-17a-5p vs. TAV. In all patients, we found an inverse correlation of MiRNA-196-5p with High-Density Lipoprotein-Cholesterol (HDL-C) and indexed valvular area. In subjects with a higher expression of miRNA196, lower levels of HDL-C correlation (r2) [r2 0.27 (p = 0.02)] and a lower indexed valvular area [r2 0.28 (p = 0.05)] were observed. In the specific analysis for each patient group, it was found that in control subjects with tricuspid aortic valve (TAV), miRNA-196-5p had a positive correlation with valvular calcification (r2 = 0.60, p = 0.02). Deregulation of miRNAs in the aortic tissue of a BAV may influence valvular stenosis, dysfunction, and concomitant aortic dilation. This information could help to define potential therapeutic target strategies to improve the prognosis and treatment of BAV.

Thermally Triggered Double Emulsion-Integrated Hydrogel Microparticles for Multiplexed Molecular Diagnostics.

During the COVID-19 pandemic, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been recognized as the most reliable diagnostic tool. However, there is a need to develop multiplexed assays capable of analyzing multiple genes simultaneously to expand its application. To address this, a multiplexed RT-qPCR using a double emulsion (DE)-based carrier and a polymer microparticle reactor, termed primer-incorporated network tailored with Taqman probe (TaqPIN) is developed. The DE securely stores nucleic acid reagents like primers and probes within the polymer network until heating releases them for the reaction. The TaqPIN RT-qPCR demonstrates an amplification efficiency of 93.8% and can detect as few as 20 copies/µL. By loading the multiple microparticles into a single reaction, a multiplexed assay with only one optical channel is enabled. In practice, a nine-plex assay is designed to distinguish between variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even subtle variations of a single nucleotide can be simultaneously detected. Testing on 75 nasopharyngeal swab samples yields 100% sensitivity and specificity for SARS-CoV-2 detection and 94% accuracy in variant discrimination.

Distinguishing Ideal and Non-Ideal Chemical Systems Based on Kinetic Behavior.

This paper focuses on differentiating between ideal and non-ideal chemical systems based on their kinetic behavior within a closed isothermal chemical environment. Non-ideality is examined using the non-ideal Marcelin-de Donde model. The analysis primarily addresses 'soft' non-ideality, where the equilibrium composition for a reversible non-ideal chemical system is identical to the corresponding composition for the ideal chemical system. Our approach in distinguishing the ideal and non-ideal systems is based on the properties of the special event, i.e., event, the time of which is well-defined. For the single-step first-order reaction in the ideal system, this event is the half-time-decay point, or the intersection point. For the two consecutive reversible reactions in the ideal system, A ↔ B ↔ C, this event is the extremum obtained within the conservatively perturbed equilibrium (CPE) procedure. For the non-ideal correspondent models, the times of chosen events significantly depend on the initial concentrations. The obtained difference in the behavior of the times of these events (intersection point and CPE-extremum point) between the ideal and non-ideal systems is proposed as the kinetic fingerprint for distinguishing these systems.

Simultaneous Ring-Opening and Dehydrogenation of Diarylethene Induced by Tunneling Electrons.

Understanding the reversible transformation between two isomeric states of organic molecules under external stimulation is essential for advancing single-molecule device development. Photochromic diarylethene (DAE) derivatives are promising candidates for single molecular switching elements. This study investigates the single-molecule reactions of the closed-form isomer of a DAE derivative on Cu(111) using scanning tunneling microscopy (STM). A novel ring-opening pathway, distinct from the well-known photochromic isomerization, was discovered. Electron injection into the lowest unoccupied molecular orbitals induces the sequential anchoring of molecules to the substrate through the dehydrogenation of a methyl group at the 2-position of the thiophene ring. This mechanism was revealed by density functional theory calculations and STM simulations. The adsorption configurations for singly and doubly dehydrogenated DAEs were identified. Based on these findings, a new reaction mechanism extending beyond reversible isomeric reactions is proposed for DAE on Cu(111). The present work establishes a novel framework for future studies on single-molecule switching phenomena on metal substrates.

Wastewater Monitoring During the COVID-19 Pandemic in the Veneto Region, Italy: Longitudinal Observational Study.

As the COVID-19 pandemic has affected populations around the world, there has been substantial interest in wastewater-based epidemiology (WBE) as a tool to monitor the spread of SARS-CoV-2. This study investigates the use of WBE to anticipate COVID-19 trends by analyzing the correlation between viral RNA concentrations in wastewater and reported COVID-19 cases in the Veneto region of Italy. We aimed to evaluate the effectiveness of the cumulative sum (CUSUM) control chart method in detecting changes in SARS-CoV-2 concentrations in wastewater and its potential as an early warning system for COVID-19 outbreaks. Additionally, we aimed to validate these findings over different time periods to ensure robustness. This study analyzed the temporal correlation between SARS-CoV-2 RNA concentrations in wastewater and COVID-19 clinical outcomes, including confirmed cases, hospitalizations, and intensive care unit (ICU) admissions, from October 2021 to August 2022 in the Veneto region, Italy. Wastewater samples were collected weekly from 10 wastewater treatment plants and analyzed using a reverse transcription-quantitative polymerase chain reaction. The CUSUM method was used to detect significant shifts in the data, with an initial analysis conducted from October 2021 to February 2022, followed by validation in a second period from February 2022 to August 2022. The study found that peaks in SARS-CoV-2 RNA concentrations in wastewater consistently preceded peaks in reported COVID-19 cases by 5.2 days. Hospitalizations followed with a delay of 4.25 days, while ICU admissions exhibited a lead time of approximately 6 days. Notably, certain health care districts exhibited stronger correlations, with notable values in wastewater anticipating ICU admissions by an average of 13.5 and 9.5 days in 2 specific districts. The CUSUM charts effectively identified early changes in viral load, indicating potential outbreaks before clinical cases increased. Validation during the second period confirmed the consistency of these findings, reinforcing the robustness of the CUSUM method in this context. WBE, combined with the CUSUM method, offers valuable insight into the level of COVID-19 outbreaks in a community, including asymptomatic cases, thus acting as a precious early warning tool for infectious disease outbreaks with pandemic potential.

A decade-long analysis of 98 chronic myeloid leukemia patients: Laboratory data and clinical progress at a single center

Abstract: BACKGROUND: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene). CML primarily progresses through chronic, accelerated, and blast phases. While global studies on BCR-ABL1 fusion transcript types and their associations with clinical, laboratory, and prognostic profiles exist, such data is scarce in Malaysia. OBJECTIVES: This study aimed to determine the distribution of BCR-ABL1 fusion transcript types and evaluate their associations with demographic, clinical, laboratory, prognostic profiles, and disease outcomes among Malaysian CML patients. PATIENTS, MATERIALS AND METHODS: A total of 98 patients diagnosed with CML were identified at East Coast Hospital, Malaysia. This 12-year cross-sectional study was carried out using data extracted from patients’ medical records. Molecular results for BCR-ABL1 fusion genes were obtained using one-step multiplex reverse transcriptase polymerase chain reaction. RESULTS: Out of the 98 patients, 56% had e14a2, 41% had e13a2 fusion transcripts, while the remaining 2 patients had e14a3 transcripts. Additionally, 1 patient co-expressed both e13a2 and e14a2. Among patients with the major BCR-ABL1 transcript type, those with e14a2 fusion transcripts showed an older median age (P = 0.025), while patients with e13a2 fusion transcripts had significantly higher white blood cell (WBC) counts (P = 0.014). Furthermore, there were significantly more patients with blastic transformation in the e13a2 group (P = 0.038). The median latency period of CML was 12 months. The blast cell lineages consisted of myeloid (68.4%), followed by B-lymphoid (26.3%) and mixed phenotypic (5.3%). The differences in fusion transcript expression might influence certain parameters; for instance, older patients were associated with the e14a2 fusion transcript. Meanwhile, patients exhibiting e13a2 might have a higher WBC count at diagnosis and be more vulnerable to blastic transformation of CML. CONCLUSIONS: This study highlights the predominance of e14a2 fusion transcripts in Malaysian CML patients and its association with older age. The e13a2 transcript was linked to higher tumor burden and a higher rate of blastic transformation, suggesting potential prognostic significance. These findings underscore the importance of baseline molecular profiling for optimizing disease management.

Combined exercise-induced modulation of Notch pathway and muscle quality in senescence-accelerated mice.

The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.

Exploring the role of ELOVLs family in lung adenocarcinoma based on bioinformatic analysis and experimental validation

BackgroundThe role of lipid metabolic reprogramming in the development of various types of cancer has already been established. However, the exact biological function and significance of the elongation of very-long-chain fatty acids (ELOVLs) gene family, which can affect fatty acid metabolism, is still not well understood in lung adenocarcinoma (LUAD). The aim of our study is to explore whether there are genes related to the pathogenesis of LUAD in the ELOVLs family, and even to guide clinical medication and potential prognostic indicators.MethodsGene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), cBioPortal, Kaplan–Meier (KM) plotter, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm and SubMap algorithms were utilized to analyze the role of ELOVLs in the LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, cell counting kit-8 (CCK8), colony formation, wound healing, transwell migration assays and fatty acid metabolism detection were employed to confirm the significant role of ELOVL6 in vitro experiment.ResultsOur results revealed that mRNA expression levels of ELOVL2, ELOVL4 and ELOVL6 and protein expression levels of ELOVL5 and ELOVL6 were elevated in LUAD tissues compared to normal subjects. The low-expressing ELOVL6 group showed superior overall survival (OS) and disease-specific survival (DSS) versus the high-expressing group. Meanwhile, patients with low-ELOVL6 expression were more sensitive to the 4 representative chemotherapeutic agents. In vitro, we revealed that interfering with ELOVL6 could influence the viability, proliferation, migration capacity and fatty acid metabolism of LUAD cells (A549 and H1299).ConclusionsOur study indicated that ELOVL6 could be used as an indicator to evaluate the prognosis and therapeutic effect, and even potential therapeutic target for patients with LUAD.

Ethyl Acetate Extract of Cichorium glandulosum Activates the P21/Nrf2/HO-1 Pathway to Alleviate Oxidative Stress in a Mouse Model of Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as a key driver. The ethyl acetate extract of Cichorium glandulosum (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism of action against ALD remains unclear. This study investigates the effects and mechanisms of CGE in alleviating alcohol-induced oxidative stress and liver injury. Ultra-Performance Liquid Chromatography coupled with Quadrupole-Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap-MS) was used to identify CGE components. A C57BL/6J mouse model of ALD was established via daily oral ethanol (56%) for six weeks, with CGE treatment at low (100 mg/kg) and high doses (200 mg/kg). Silibinin (100 mg/kg) served as a positive control. Liver function markers, oxidative stress indicators, and inflammatory markers were assessed. Transcriptomic and network pharmacology analyses identified key genes and pathways, validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. UPLC-Q-Orbitrap-MS identified 81 CGE compounds, mainly including terpenoids, flavonoids, and phenylpropanoids. CGE significantly ameliorated liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and enhancing antioxidative markers such as total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) while lowering hepatic malondialdehyde (MDA) levels. Inflammation was mitigated through reduced levels of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1 Beta (IL-1β), and C-X-C Motif Chemokine Ligand 10 (CXCL-10). Transcriptomic and network pharmacology analysis revealed seven key antioxidant-related genes, including HMOX1, RSAD2, BCL6, CDKN1A, THBD, SLC2A4, and TGFβ3, validated by RT-qPCR. CGE activated the P21/Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) signaling axis, increasing P21, Nrf2, and HO-1 protein levels while suppressing Kelch-like ECH-associated Protein 1 (Keap1) expression. CGE mitigates oxidative stress and liver injury by activating the P21/Nrf2/HO-1 pathway and regulating antioxidant genes. Its hepatoprotective effects and multi-target mechanisms highlight CGE's potential as a promising therapeutic candidate for ALD treatment.

Establishment of liquid-liquid phase separation-related prognostic model in lung adenocarcinoma and systematic analysis of its clinical significance.

To detect the prognostic importance of liquid-liquid phase separation (LLPS) in lung adenocarcinoma. The gene expression files, copy number variation data, and clinical data were downloaded from The Cancer Genome Atlas cohort. LLPS-related genes were acquired from the DrLLPS website. The prognostic model based on LLPS was constructed by the Cox regression and LASSO regression analyses after the identification of LLPS-related differentially expressed genes (DEGs). Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The LLPS-related prognostic risk score was validated by GSE31210 and GSE72094. The overall survival of lung adenocarcinoma patients was predicted by plotting a nomogram. The biological features of the high-risk lung adenocarcinoma were evaluated by the CIBERSORT, ESTIMATE, Gene Set Variation Analysis, and Genomics of Drug Sensitivity in Cancer. Reverse transcription-quantitative polymerase chain reaction detected hub gene expression. A total of 91 DEGs were screened out in LLPS, among which 9 genes were discovered as prognostic biomarkers of lung adenocarcinoma. GRIA1, CRTAC1, MAGEA4, and MAPK4 were identified as hub genes by the LASSO Cox regression analysis. High-risk and low-risk groups were divided according to the risk index, with the high-risk group displaying a markedly worse outcome. CRTAC1 expression was significantly decreased, MAGEA4 and MAPK4 expressions were increased, while GRIA1 expression was altered in lung adenocarcinoma cells. Tumor microenvironment, signaling pathway enrichment, and drug sensitivity significantly differed between different risk groups. This work proposed a prognostic tool based on the LLPS-related gene signature to offer prospective and effective biomarkers for lung adenocarcinoma prognosis.

Investigating the Immunogenic Properties of a Mutagenized NS3/4A-Based HCV Genotype 3a DNA Vaccine.

Chronic hepatitis C virus (HCV) infection poses a major health risk worldwide, with patients susceptible to liver cirrhosis and hepatocellular carcinoma. This study focuses on the development of effective therapeutic strategies for HCV infection through the investigation of immunogenic properties of a DNA construct based on the NS3/4A gene of HCV genotype (g)3a. Gene expression of the mutagenized (mut) NS3/4A target genes was assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Additionally, bioinformatics tools were employed to evaluate the impact of the mut-NS3/4A-based DNA vaccine. Analysis revealed increased mut-NS3/4A mRNA levels and target protein abundance compared with the native sequence. Elevated mut-NS3/NS4A levels could result from increased RNA stability and proper protein folding. Physicochemical analyses of the protein demonstrated favorable attributes such as thermostability and solubility. Three-dimensional mut-NS3/4A protein modeling confirmed its high stability and agreement with known protein structures. Additionally, potential immunogenic regions of both T and B cell epitopes were discovered based on peptide binding to major histocompatibility complex molecules of Asian origin. Importantly, these epitopes exhibited nonallergenic and nontoxic characteristics. These findings highlight the potential of the NS3/4A-based DNA construct as a promising candidate for an HCVg3a vaccine tailored for the Asian population, providing valuable insights for future immunotherapeutic approaches.

Radionuclide sorption dynamics in the Rhone River: Experimental and modelling approach.

The transfer of radionuclides discharged into rivers by nuclear facilities are conditioned by their solid/liquid fractionation, commonly represented by an equilibrium approach using the distribution coefficient Kd. This coefficient, largely used in modeling, assumes an instantaneous and completely reversible reaction. However, such assumptions are rarely verified. Compared to instantaneous adsorption of radionuclides onto particles, slower reactions may lead to an underestimation of the dissolved fraction, and modifications of environmental conditions (e.g. at confluences, dams …) may induce a change in solid/liquid partition. Considering this background, this study aims to assess whether models incorporating one or more kinetics to describe this fractionation allow more accurate estimations than the equilibrium approach. A large dataset has been obtained experimentally to compare and test fractionation models. The exchanges of four radionuclides (137Cs, 60Co, 54Mn, and 110mAg) between solution and riverine suspended particulate matter (from the Rhone River, France) were followed in laboratory. Adsorption kinetics were monitored starting from 30min up to 2 months. They stabilized only after several days and up to 2 weeks. Dilutions of the contaminated suspension were carried out after 1h, 3 days, 10, 21 and 31 days of prior adsorption, to simulate a change in environmental conditions, such as the input of uncontaminated water from a tributary. The dilution induced a quick release from solid to liquid at first, followed by a non-expected re-adsorption for all four radionuclides. 31-days sorption data were used to fit the parameters of a Kd model and derived models involving one (EK) or two fractionation kinetics (KK). Predictions were then carried out to evaluate the model capacities to react to a dilution of the contamination. Unlike the Kd model, which is a constant, the kinetic models predicted a variation in the solid/liquid activity ratio over time and when environmental conditions changed. However, models developed on one-step sorption showed limitations to reproduce the adsorption kinetics observed after a dilution, especially when a previous steady-state was reached.

Evaluation of Salivary and Serum micro RNA 146a, 200c and its Target Gene PTEN in Chronic Periodontitis Patients and their Response to Non-Surgical Periodontal Therapy.

Periodontitis destroys the tooth's supporting structures and attachment apparatus. Local or systemic factors can cause it. Traditionally, diagnosis is based on clinical parameters that may not consistently reflect an accurate confirmation. Biochemical and genetic analyses can provide deeper insights. MicroRNAs (miRNAs) regulate the immune and inflam-matory response to microbial pathogens. Detecting and evaluating miRNAs can be an important diagnostic parameter. This study aimed to assess the expression of miRNA 146a,200c, and its target gene PTEN to non-surgical periodontal therapy in serum and saliva. This interventional comparative study was conducted on 120 patients of both genders, ages between 35 and 55. Non-surgical periodontal therapy (NSPT) scaling and root planing were performed on all subjects, and their saliva and serum samples were collected before and after 8 weeks of NSPT. Quantitative rt-PCR (reverse transcriptase Polymerase Chain Reaction) analysis was conducted on all samples. The statistical analysis was done using SPSS version 22, and comparisons were made using paired t-tests, independent t-tests, and Pearson's correlation coefficient. The statistical significance level was set at a 'P' value of less than 0.05. It has been observed that there was a significant difference of miRNA in both serum and saliva samples 146a,200c, and the PTEN gene expression, from the beginning to 8 weeks. Sig-nificant variation was not observed when comparing the levels between serum and saliva. miRNA 146A, 200c, and PTEN genes are interrelated with periodontitis. We can consider them as future biomarkers of periodontal diseases.