A Case Report of Hemiplegic Migraine with Mutation in the ATP1A2 Gene.

Background: Hemiplegic migraine, a less common variant of migraine, is the focus of this paper. Within the scope of this study, we present a case of hemiplegic migraine that bears the potential for misdiagnosis, particularly as encephalitis. Brief introduction to the Disease: The patient developed a right-sided headache a day prior to admission, accompanied by fever, nausea, vomiting, and left-sided limb weakness. On the fourth day, the patient experienced a grand mal epilepsy, marked by unconsciousness, leftward deviation of both eyes, limb convulsions, and foaming at the mouth. Cerebrospinal fluid analysis revealed no apparent abnormalities, Electroencephalography showed abnormal slow waves, imaging studies indicated swelling and meningeal thickening in the right cortex, and genetic testing identified a heterozygous mutation in the ATPIA2 gene. The diagnosis was hemiplegic migraine, and the patient received symptomatic supportive treatment, leading to improvement and subsequent discharge. Flunarizine and sodium valproate were prescribed post-discharge, and the patient achieved complete recovery after a one-month follow-up. Conclusion: Apart from experiencing headaches, patients with hemiplegic migraine may exhibit additional symptoms like fever, epilepsy, and hemiplegia. These manifestations warrant clinical attention, and if deemed necessary, genetic testing should be conducted, and this is an autosomal dominant pattern.

Understanding the impact of witnessed workplace mistreatment: A meta-analysis of observer deontic reactions and employee outcomes.

This meta-analysis aims to understand the impact of witnessed workplace mistreatment. Bringing together two streams of research, it examines (a) the boundary conditions of observer reactions that reflect a principled moral disapproval of violations of interpersonal justice (i.e., deontic reactions) and (b) the extent to which witnessed mistreatment explains incremental variance in a range of employee outcomes beyond the effects of experienced mistreatment. The results demonstrate that observer psychological and behavioral deontic reactions are not straightforward. For example, while observers have negative reactions toward perpetrators, they fail to intervene and have mixed reactions toward targets. Findings from a series of moderator analyses illuminate the role of perpetrator rank, mistreatment severity, and study context in explaining these disparate observer deontic reactions. Further, although experienced mistreatment explains more variance in most employee outcomes than witnessed mistreatment, witnessed mistreatment still has a unique and sizable contribution. The implications of these findings and future directions for research on witnessed mistreatment are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical insights into tuberculosis otitis media: diagnosis, treatment, and management outcomes.

OBJECTIVES: The diagnosis of tuberculosis otitis media (TBOM) remains a great challenge. This study aims to suggest potential diagnostic clues and proper management of TBOM. METHODS: The study is a retrospective review of TBOM cases that were treated at our department, between January 2015 and June 2023. Summarizing their clinical characteristics, diagnosis, and treatment. Additionally, a literature review is conducted. RESULTS: Eight cases of TBOM, 6 female and 2 male patients, median age was 32 years old, were included in the study. TBOM mainly presents with symptoms of otorrhea, hearing loss, and occasional early-onset facial palsy. One case had a positive Purified Protein Derivative (PPD) before the operation. Middle ear tissue was pathologically biopsied in 7 cases, with 3 cases testing positive for Acid Fast Bacillus and 6 cases testing positive for Mycobacterium tuberculosis PCR. Middle ear surgery and Anti-tubercular treatment (ATT) were completed in all cases. The median follow-up was 11 months. No cases of TB relapse were observed. CONCLUSIONS: Proper suspicion and confirmation of TBOM is the primary clinical orientation. Middle ear surgery combination with ATT results in satisfactory outcomes. Hearing reconstruction should be performed after ATT is completed.

Synergy of Ag and Interfacial Oxygen Vacancies on TiO2 for Highly Efficient Photocatalytic Production of H2O2.

Photocatalytic H2O2 production stands as a promising sustainable technology for chemical synthesis. However, rapid charge recombination and limited oxygen adsorption by photocatalysts often limit its efficiency. Herein, we demonstrate that the synergy of Ag and interfacial oxygen vacancies on TiO2 could overcome these challenges. The optimized Ag/TiO2-50 photocatalyst achieved an impressive H2O2 production rate of 12.9 mmol h-1 g-1 and maintained a steady-state concentration of 12.8 mM, significantly outperforming most TiO2-based photocatalysts documented in the literature. Detailed mechanistic studies, aided by TAS, in situ X-ray photoelectron spectroscopy (XPS), and in situ electron paramagnetic resonance (EPR) techniques, indicate that the oxygen vacancies at the Ag-TiO2 interface act as an interfacial hole trap, inducing a directional hole transfer. This, coupled with Ag acting as an electron acceptor, synergistically boosts the electron-hole separation. Additionally, the increased amount of oxygen vacancies at the Ag-TiO2 interface of Ag/TiO2-50 leads to enhanced O2 adsorption, thus contributing to its superior catalytic performance. This study provides valuable insights into interfacial traps in the charge transfer process and highlights the potential of interface regulation for achieving efficient photocatalytic conversion.

ZFP64 drives glycolysis-mediated stem cell-like properties and tumorigenesis in breast cancer.

BACKGROUND: Breast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway. RESULTS: It was demonstrated that ZFP64 was overexpressed in BC specimens compared to adjacent normal tissues, and patients with high ZFP64 expression had shorter overall survival and disease-free survival. The analysis of the association of ZFP64 expression with clinicopathological characteristics showed that high ZFP64 expression is closely associated with N stage, TNM stage, and progesterone receptor status. Knockdown of ZFP64 suppressed the viability and colony formation capacity of BC cells by CCK8 and colony formation assays. The subcutaneous xenograft models revealed that ZFP64 knockdown reduced the volume of formatted tumors, and decreased Ki67 expression in tumors. The opposite effects on cell proliferation and tumorigenesis were demonstrated by ZFP64 overexpression. Furthermore, we suggested that the stem cell-like properties of BC cells were inhibited by ZFP64 depletion, as evidenced by the decreased size and number of formatted mammospheres, the downregulated expressions of OCT4, Nanog, and SOX2 proteins, as well as the reduced proportion of CD44+/CD24- subpopulations. Mechanistically, glycolysis was revealed to mediate the effect of ZFP64 using mRNA-seq analysis. Results showed that ZFP64 knockdown blocked the glycolytic process, as indicated by decreasing glycolytic metabolites, inhibiting glucose consumption, and reducing lactate and ATP production. As a transcription factor, we identified that ZFP64 was directly bound to the promoters of glycolysis-related genes (ALDOC, ENO2, HK2, and SPAG4), and induced the transcription of these genes by ChIP and dual-luciferase reporter assays. Blocking the glycolytic pathway by the inhibition of glycolytic enzymes ENO2/HK2 suppressed the high proliferation and stem cell-like properties of BC cells induced by ZFP64 overexpression. CONCLUSIONS: These data support that ZFP64 promotes stem cell-like properties and tumorigenesis of BC by activating glycolysis in a transcriptional mechanism.

Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice.

INTRODUCTION: The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aß) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored. METHODS: Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age. RESULTS: Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aß load. Single nucleus RNA sequencing analysis revealed that in the absence of Trem2, microglia were activated but trapped in transition to the fully reactive state, with distinct responses of vascular cells. DISCUSSION: Our study provides the first evidence that TREM2 differentially modulates parenchymal and vascular Aß pathologies, offering significant implications for both TREM2- and Aß-targeting therapies for AD. HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) differentially modulates brain parenchymal and vascular amyloidosis. Loss of Trem2 markedly reduces cerebral amyloid angiopathy despite an overall increase of amyloid beta load in Tg-SwDI mice. Microglia are trapped in transition to the fully reactive state without Trem2. Perivascular macrophages and other vascular cells have distinct responses to Trem2 deficiency. Balanced TREM2-targeting therapies may be required for optimal outcomes.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. OBJECTIVE: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses. DATA SOURCES: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. ELIGIBILITY CRITERIA: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. RESULTS: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation (P < 0.01, I2 = 82%). No significant difference was found between different control drugs (P = 0.97, I2 = 82%). CONCLUSION: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Association of baseline sleep duration and sleep quality with seizure recurrence in newly treated patients with epilepsy.

OBJECTIVE: Although sleep duration and sleep quality are considered to be significant factors associated with epilepsy and seizure risk, findings are inconsistent, and their joint association remains uncertain. This study aimed to determine independent and joint associations of these two modifiable sleep features with seizure recurrence risk in newly treated patients with epilepsy (PWE). METHODS: This is a prospective cohort study of newly treated PWE at a comprehensive epilepsy center in northeast China between June 2020 and December 2023. Self-reported sleep duration and sleep quality were collected at baseline. All patients were followed for 12 months for recurrent seizures. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of seizure recurrence. Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. RESULTS: A total of 209 patients were included, and 103 experienced seizure recurrence during follow-up. Baseline short sleep was significantly associated with greater risk of seizure recurrence (adjusted HR = 2.282, 95% confidence interval [CI] = 1.436-3.628, p < .001). Sleep duration (h/day) and recurrent seizure risk showed a significant nonlinear U-shaped association, with a nadir at 8 h/day. Baseline poor sleep quality was significantly associated with greater risk of seizure recurrence (adjusted HR = 1.985, 95% CI = 1.321-2.984, p < .001). Pittsburgh Sleep Quality Index score and seizure recurrence risk exhibited a positive linear association. Participants with a combination of poor quality-short sleep showed the highest risk of seizure recurrence (adjusted HR = 3.13, 95% CI = 1.779-5.507, p < .001) compared to the referent good quality-intermediate sleep group. SIGNIFICANCE: Baseline sleep duration and sleep quality were independently and jointly associated with risk of seizure recurrence in newly treated PWE. Our results point to an important potential role of baseline sleep duration and sleep quality in shaping seizure risk.

Surgical treatment strategies for ankylosing spondylitis with "folded man" deformity: A Single-Center Retrospective Case Series Study.

OBJECTIVE: Ankylosing spondylitis (AS) combined with severe kyphotic deformity can cause the trunk to collapse, pressing tightly against the front of the thighs and forming a "folded man" deformity. The purpose of this article is to evaluate the effectiveness and safety of a treatment strategy for correcting the "folded man" deformity. METHODS: A retrospective study was conducted to analyze 12 AS patients with "folded man" deformity treated at our hospital with staged kyphosis correction in the lateral position, followed by total hip arthroplasty, from May 2018 to July 2021. Global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), chin-brow vertical angle (CBVA), and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) scores were compared pre- and post-operation. Surgical duration, positioning time, blood loss, and complications were also recorded and analyzed. RESULTS: All patients demonstrated a correction of the "folded man" deformity, achieving sagittal balance and horizontal gaze with mild complications. Postoperatively, there were significant improvements in spinal sagittal parameters (GK, TK, LL, SVA) and CBVA compared to preoperative values (P < 0.05). The preoperative GK of 139.6 ± 9.1° was corrected to 55.3 ± 5.7° postoperatively,with a mean correction of 84.3°. CONCLUSION: The standardized treatment strategy involving staged correction of spinal kyphosis in a lateral position, followed by subsequent total hip arthroplasty, offers a safe and effective solution for managing ankylosing spondylitis with "folded man" deformity.

Nanosized Porphyrin-Containing Covalent Organic Polymer to Enhance Ferroptosis in Photodynamic Treatment of Tumor Cells via Glutathione Depletion.

A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.

Mitochondrial dysfunction in diabetic nephropathy: insights and therapeutic avenues from traditional Chinese medicine.

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Most of the energy we need comes from mitochondria. Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. The pathogenesis of DN involves a variety of factors, such as altered haemodynamics, oxidative stress, and inflammation, and studies from animal models suggest that mitochondrial dysfunction plays an important role in the development of DN. Traditional Chinese medicine (TCM) has a history of more than 2,500 years and has rich experience and remarkable efficacy in the treatment of DN. Recent studies have found that TCM may have great potential in regulating mitochondrial dysfunction in the treatment of DN. This review will elucidate the main causes of mitochondrial dysfunction and the relationship with DN, and explore in depth the potential mechanisms of TCM to protect the kidney by improving mitochondrial dysfunction. Current pharmacological treatments for patients with DN do not prevent the inevitable progression to ESRD. With the rich variety of Chinese herbs, TCM is expected to be the most promising candidate for the treatment of DN as we continue to learn more about the mechanisms of DN and incorporate the current advances in extraction techniques.

10-Dibenzothiophenyl-9,9-diphenylacridane-based multiple resonance emitters for high-efficiency narrowband green OLEDs with CIE y > 0.7 at high doping concentrations.

Multiple resonance emitters are attractive for high-color-purity organic light-emitting diodes (OLEDs) because of their unique narrowband emissions; however, they are typically used at low doping concentrations (≤15 wt%) due to aggregation-caused quenching and spectral broadening induced by planar molecular skeletons. Here, we report two multiple resonance emitters (BThPAc-1 and BThPAc-2) consisting of a 10-dibenzothiophenyl-9,9-diphenylacridane segment for efficient narrowband green emission at high doping concentrations. The dibenzothiophenyl-9,9-diphenylacridane segment contains two carbon-bridged phenyl rings as steric groups to inhibit intermolecular aggregation and a dibenzothiophene unit to extend conjugation and red-shift the emission to the green region. The resultant emitters exhibit narrowband emissions that peaked at 509-510 nm with a full width at half-maximum (FWHM) of 32 nm in 1 wt% doping films, which are maintained at less than 35 nm even in neat films. Remarkably, OLEDs employing the emitters reveal pure-green electroluminescence with a maximum external quantum efficiency of 20.3% and CIE coordinates of (0.18, 0.72) at 30 wt% doping concentration, which represents the best color coordinates for green multiple resonance OLEDs at high doping concentrations.

Cyclic Multi-Site Chelation for Efficient and Stable Inverted Perovskite Solar Cells.

Trap-assisted non-radiative recombination losses and moisture-induced degradation significantly impede the development of highly efficient and stable inverted (p-i-n) perovskite solar cells (PSCs), which require high-quality perovskite bulk. In this research, we mitigate these challenges by integrating thermally stable perovskite layers with Lewis base covalent organic frameworks (COFs). The ordered pore structure and surface binding groups of COFs facilitate cyclic, multi-site chelation with undercoordinated lead ions, enhancing the perovskite quality across both its bulk and grain boundaries. This process not only reduces defects but also promotes improved energy alignment through n-type doping at the surface. The inclusion of COF dopants in p-i-n devices achieves power conversion efficiencies (PCEs) of 25.64% (certified 24.94%) for a 0.0748-cm2 device and 23.49% for a 1-cm2 device. Remarkably, these devices retain 81% of their initial PCE after 978 hours of accelerated aging at 85˚C, demonstrating remarkable durability. Additionally, COF-doped devices demonstrate excellent stability under illumination and in moist conditions, even without encapsulation.

An efficient improved parrot optimizer for bladder cancer classification.

Bladder Cancer (BC) is a common disease that comes with a high risk of morbidity, death, and expense. Primary risk factors for BC include exposure to carcinogens in the workplace or the environment, particularly tobacco. There are several difficulties, such as the requirement for a qualified expert in BC classification. The Parrot Optimizer (PO), is an optimization method inspired by key behaviors observed in trained Pyrrhura Molinae parrots, but the PO algorithm becomes stuck in sub-regions, has less accuracy, and a high error rate. So, an Improved variant of the PO (IPO) algorithm was developed using a combination of two strategies: (1) Mirror Reflection Learning (MRL) and (2) Bernoulli Maps (BMs). Both strategies improve optimization performance by avoiding local optimums and striking a compromise between convergence speed and solution diversity. The performance of the proposed IPO is evaluated against eight other competitor algorithms in terms of statistical convergence and other metrics according to Friedman's test and Bonferroni-Dunn test on the IEEE Congress on Evolutionary Computation conducted in 2022 (CEC 2022) test suite functions and nine BC datasets from official repositories. The IPO algorithm ranked number one in best fitness and is more optimal than the other eight MH algorithms for CEC 2022 functions. The proposed IPO algorithm was integrated with the Support Vector Machine (SVM) classifier termed (IPO-SVM) approach for bladder cancer classification purposes. Nine BC datasets were then used to confirm the effectiveness of the proposed IPO algorithm. The experiments show that the IPO-SVM approach outperforms eight recently proposed MH algorithms. Using the nine BC datasets, IPO-SVM achieved an Accuracy (ACC) of 84.11%, Sensitivity (SE) of 98.10%, Precision (PPV) of 95.59%, Specificity (SP) of 95.98%, and F-score (F1) of 94.15%. This demonstrates how the proposed IPO approach can help to classify BCs effectively. The open-source codes are available at https://www.mathworks.com/matlabcentral/fileexchange/169846-an-efficient-improved-parrot-optimizer.

Characterization of the MicroRNA profile in rheumatoid arthritis plasma exosomes and their roles in B-cell responses.

OBJECTIVE: This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles. METHODS: Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments. RESULTS: Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production. CONCLUSION: The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.

[Assessment of carbon reduction and sink enhancement potential of photovoltaic+mining ecological restoration model]. / å ‰ä¼+矿山生态修复模式的减碳增汇潜力评估.

The energy oriented mine ecological restoration mode of photovoltaic+ecological restoration provides a breakthrough for alleviating the dilemma of photovoltaic land development and solving the urgent need for restoration of abandoned mining land. Taking a mining area in central Liaoning Province as an example, we established three photovoltaic+mining ecological restoration modes, including forest-photovoltaic complementary, agriculture-photovoltaic, and grass photovoltaic complementation. Combined with the life cycle assessment method, we calculated and assessed the potential of photovoltaic+mining ecological restoration in carbon reduction and sink enhancement. The average annual carbon reduction and sink increase was 514.93 t CO2·hm-2 under the photovoltaic+mining ecological restoration mode, while the average annual carbon reduction per megawatt photovoltaic power station was 1242.94 t CO2. The adoption of photovoltaic+ecological restoration mode in this mining area could make carbon reduction and sink enhancement 6.30-7.79 Mt CO2 during 25 years. The carbon reduction and sink increment mainly stemmed from the photovoltaic clean power generation induced carbon reduction, accounting for 96.4%-99.4%, while the contribution of ecosystem carbon sink increment was small, accounting for only 0.6%-3.7% of the total. Among different photovoltaic+ecological restoration modes, the carbon reduction and sink increment was the largest in forest-photovoltaic complementary (7.11 Mt CO2), followed by agriculture-photovoltaic (7.04 Mt CO2), and the least in grass photovoltaic complementation (6.98 Mt CO2). Constructing the development mode of "photovoltaic+mining ecological restoration" could effectively leverage the dual benefits of reducing emissions from photovoltaic power generation and increase sinks from mining ecological restoration, which would be helpful for achieving the goal of carbon neutrality in China.

Roundup® induces premature senescence of mouse granulosa cells via mitochondrial ROS-triggered NLRP3 inflammasome activation.

Roundup, a glyphosate-based herbicide widely used in agriculture, has raised concerns regarding its potential impact on human health due to the detection of its residues in human urine and serum. Granulosa cells are essential for oocyte growth and follicle development. Previous research has shown that Roundup could affect steroid synthesis, increases oxidative stress, and induces apoptosis in granulosa cells. However, little is known about the effects of Roundup on NLRP3 (nucleotide binding oligomerization domain-like receptor family pyrin-containing domain protein 3) inflammasome activation and cellular senescence in granulosa cells. Here, we provided evidence that exposure to Roundup induced premature senescence in mouse granulosa cells through the activation of NLRP3 inflammasome triggered by mitochondrial ROS. Our findings demonstrated that Roundup significantly reduced the viability of granulosa cells under in vitro culture conditions. It also disrupted mitochondrial function and induced oxidative stress in these cells. Subsequent investigations showed that NLRP3 inflammasome was activated in treated granulosa cells, as evidenced by the upregulation of inflammasome-related genes and the processing of inflammatory cytokines IL-1ß and IL-1α into their mature forms. Consequently, premature cellular senescence occurred in response to the challenge posed by Roundup. Notably, direct inhibition of NLRP3 inflammasome with MCC950 does not alleviate mitochondrial damage and oxidative stress. However, supplementation of resveratrol, which has been known to attenuate mitochondrial damage and oxidative stress, effectively mitigated the inflammatory response and the expression of senescence-related markers, and prevented the senescence in granulosa cells. These results suggested that mitochondrial function and oxidative homeostasis might play pivotal roles as upstream regulators of NLRP3 inflammasome. In summary, our findings indicated that the premature senescence of granulosa cells caused by mitochondrial ROS-triggered NLRP3 inflammasome activation might contribute to the ovarian toxicity of Roundup, in addition to its known effects on steroidogenesis and apoptosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00229-0.

Enhanced n-Type Thermoelectric Properties and Structure Evolution of Carbonized Metal-Coordination Polydopamine.

Carbonized polydopamine (cPDA) exhibits a nitrogenous graphite-like structure with n-type semiconductor property. However, the low electrical conductivity and Seebeck coefficient of cPDA cannot meet the needs of flexible thermoelectric devices. In this study, a series of metal ions were coordinated with cPDA to enhance n-type thermoelectric properties. At 300 K, all metal-coordination cPDA (metal-cPDA) samples obtain lower thermal conductivity compared to cPDA. Mn-cPDA exhibits the greatest Seebeck coefficient of -25.94 µV K-1, which is almost six times higher than cPDA. Fe-cPDA shows the best electrical conductivity of 2.45 × 105 S m-1. An optimal power factor (PF) value of 11.93 µW m-1 K-2 is achieved in Ca-cPDA with the enhanced electrical conductivity of 9.5 × 104 S m-1 and Seebeck coefficient of -11.24 µV K-1. Using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM), we revealed the structural characterization of metal-cPDA. Our results indictate that the different metal ions (Mn2+, Zn2+, Mg2+, Al3+, Ca2+, and Fe3+) exert varying influences on the growth of graphite-like structure within metal-cPDA, which lead to the evolution of electrical conductivity. We observe that the carrier density and carrier mobility depend on both the degree of graphitization and the metal-ion coordination, which work together on electrical conductivity and Seebeck coefficient. These findings and understanding of the thermoelectric properties of PDA-based materials will help to realize high-performance n-type thermoelectric materials for flexible electronic device applications.

The predictive value of E2F7 in immunotherapy efficacy for lung adenocarcinoma: An observational study.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. In recent years, immunotherapy has greatly changed the treatment pattern of advanced LUAD. However, only a small proportion of LUAD patients benefitted from immune checkpoint inhibitor therapy. There is an urgent need to develop a biomarker to predict immune therapy response. E2F7 has been shown to be closely related to immune cell infiltration and immune checkpoint expression in tumors. However, it is unclear whether the E2F7 expression is related to the immunotherapy efficacy in LUAD. Therefore, we conducted this study to investigate the clinical characteristics, function, and immunotherapy responsiveness of E2F7 expression, and to explore the potential of E2F7 as an immunotherapy response biomarker in LUAD. We analyzed the clinical characteristics and biological function of E2F7 expression based on data from the Cancer Genome Atlas and Gene Expression Omnibus database. In addition, we used single-cell sequencing data to analyze the immune regulatory effects of E2F7 in LUAD. Furthermore, we analyzed the immunotherapy response prediction ability of E2F7 expression based on the immunotherapy database. Compared to normal lung tissue, E2F7 was specifically overexpressed in LUAD, and its expression was associated with higher malignancy and poor efficacy. E2F7 high expression was an independent risk factor affecting the prognosis of LUAD. E2F7 was enriched in cell division and cell cycle functions. In addition, the expressions of immune checkpoints were correlated with the E2F7 expression. E2F7 was highly expressed in myeloid cells, and E2F7 highly expressed myeloid cells were associated with immune and inflammatory responses. Moreover, the expression level of E2F7 can effectively distinguish different immune therapy responses in LUAD patients. E2F7 was upregulated in LUAD, and high expression of E2F7 was associated with higher malignancy and poor efficacy. E2F7 high expression was an independent risk factor affecting the prognosis of LUAD. Moreover, E2F7 may exert its immunosuppressive effect by affecting the function of myeloid cells. These results indicated the potential role of E2F7 as a biomarker for predicting LUAD immunotherapy responses.

A polysaccharide PRCP from Rosa cymosa Tratt fruit: Structural characteristics and immunomodulatory effects via MAPK pathway modulation in vitro.

The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation.