Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas.

Background: Numerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression and function of RPN1, a crucial gene in disulfidptosis, remain unclear in the context of cancer. Methods: Gene expression and clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. RPN1 expression was analyzed using the Timer2.0 and the Human Protein Atlas (HPA) databases. Prognostic significance was assessed using Cox regression analysis and Kaplan-Meier curves. Genetic mutations and methylation levels were examined using the cBioPortal and UALCAN platforms, respectively. The relationship between RPN1 and tumor mutation burden (TMB) and microsatellite instability (MSI) across different cancer types was analyzed using the Spearman correlation coefficient. The relationship between RPN1 and immune cell infiltration was analyzed using the Timer2.0 database, whereas variations in drug sensitivity were explored using the CellMiner database. Receiver operating characteristic curves validated RPN1's diagnostic potential in glioma, and its correlation with immune checkpoint inhibitors (ICIs) was assessed using Spearman's correlation coefficient. Single-sample gene set enrichment analysis elucidated a link between RPN1 and immune cells and pathways. In addition, a nomogram based on RPN1 was developed to predict patient prognosis. The functional impact of RPN1 on glioma cells was confirmed using scratch and Transwell assays. Result: RPN1 was aberrantly expressed in various cancers and affected patient prognosis. The main mutation type of RPN1 in the cancer was amplified. RPN1 exhibited a positive correlation with myeloid-derived suppressor cells, neutrophils, and macrophages, and a negative correlation with CD8+ T cells and hematopoietic stem cells. RPN1 expression was associated with TMB and MSI in various cancers. The expression of RPN1 affected drug sensitivity in cancer cells. RPN1 was positively correlated with multiple ICIs in gliomas. RPN1 also affected immune cell infiltration into the tumor microenvironment. RPN1 was an independent prognostic factor for gliomas, and the nomogram demonstrated excellent predictive performance. Interference with RPN1 expression reduces the migratory and invasive ability of glioma cells. Conclusion: RPN1 exerts multifaceted effects on different stages of cancer, including immune infiltration, prognosis, and treatment outcomes. RPN1 expression affects the prognosis and immune microenvironment infiltration in patients with glioma, making RPN1 a potential target for the treatment of glioma.

Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.

Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

Comfort nursing theory on the postoperative rehabilitation quality and nursing satisfaction of patients with intracranial aneurysm.

To explore the influence of comfort nursing theory on the postoperative rehabilitation quality of patients with intracranial aneurysms. From October 2017 to December 2022, 315 patients with intracranial aneurysms underwent interventional surgery in our hospital were included in this retrospective study and divided into the routine group (n = 105) and comfort nursing group (n = 210) based on different nursing methods. The Glasgow Outcome Scale (GOS) was used to assess patient rehabilitation outcomes. Patients' anxiety, pain, quality of life, and their satisfaction with treatment were compared. Compared with the patients receiving routine nursing, the time for comfortable nursing patients to resume normal diet, get out of bed and exercise, and the total hospital stay were significantly shortened. And the GOS score of patients receiving comfort nursing was significantly higher than that of patients receiving routine nursing. After nursing, self-rating anxiety scale and visual analog scale scores of comfortable nursing patients were significantly lower than those of routine nursing, and Karnofsky performance status scores were significantly higher than those of routine nursing. This showed that receiving comfortable nursing was beneficial to improve perioperative anxiety and depression in patients with intracranial aneurysm, and significantly improve the quality of life of patients. The total satisfaction of comfortable nursing patients was 95.24%, while that of routine nursing patients was 76.19%. Complications occurred in 30 patients receiving routine nursing, while only 15 patients received comfort nursing. The immune indexes such as CD3+, CD4+, and CD23+ of comfortable nursing patients were significantly higher than the routine nursing patients within 1 and 5 days after operation, while the immune indexes of CD8+ were lower than the routine nursing patients 5 days after operation. Comfortable nursing from the perspective of quality nursing can significantly improve the physiological indicators of patients with intracranial aneurysms, accelerate the progress of postoperative rehabilitation, improve the anxiety, pain and quality of life of patients, and improve the satisfaction of patients with nursing. Comfort nursing from the perspective of quality nursing can reduce the occurrence of postoperative complications, which may be achieved by improving the patient's immune function.

The Combination of Hyperuricemia and Elevated High-Sensitivity C-Reactive Protein Increased the Risk of Cardiac Conduction Block.

Objective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP. Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP>3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB. Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22-1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27-2.77), and right bundle branch block (HR:1.47, 95% CI:1.02-2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP. Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP.

ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs.

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.

Toxicokinetics Explain Differential Freshwater Ecotoxicity of Nanoencapsulated Imidacloprid Compared to Its Conventional Active Ingredient.

Agricultural applications of nanotechnologies necessitate addressing safety concerns associated with nanopesticides, yet research has not adequately elucidated potential environmental risks between nanopesticides and their conventional counterparts. To address this gap, we investigated the risk of nanopesticides by comparing the ecotoxicity of nanoencapsulated imidacloprid (nano-IMI) with its active ingredient to nontarget freshwater organisms (embryonic Danio rerio, Daphnia magna, and Chironomus kiinensis). Nano-IMI elicited approximately 5 times higher toxicity than IMI to zebrafish embryos with and without chorion, while no significant difference was observed between the two invertebrates. Toxicokinetics further explained the differential toxicity patterns of the two IMI analogues. One-compartmental two-phase toxicokinetic modeling showed that nano-IMI exhibited significantly slower elimination and subsequently higher bioaccumulation potential than IMI in zebrafish embryos (dechorinated), while no disparity in toxicokinetics was observed between nano-IMI and IMI in D. magna and C. kiinensis. A two-compartmental toxicokinetic model successfully simulated the slow elimination of IMI from C. kiinensis and confirmed that both analogues of IMI reached toxicologically relevant targets at similar levels. Although nanopesticides exhibit comparable or elevated toxicity, future work is of utmost importance to properly understand the life cycle risks from production to end-of-life exposures, which helps establish optimal management measures before their widespread applications.

Neurotransmitter accumulation and Parkinson's disease-like phenotype caused by anion channelrhodopsin opto-controlled astrocytic mitochondrial depolarization in substantia nigra pars compacta.

Parkinson's disease (PD) is a mitochondria-related neurodegenerative disease characterized by locomotor deficits and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Majority of PD research primarily focused on neuronal dysfunction, while the roles of astrocytes and their mitochondria remain largely unexplored. To bridge the gap and investigate the roles of astrocytic mitochondria in PD progression, we constructed a specialized optogenetic tool, mitochondrial-targeted anion channelrhodopsin, to manipulate mitochondrial membrane potential in astrocytes. Utilizing this tool, the depolarization of astrocytic mitochondria within the SNc in vivo led to the accumulation of γ-aminobutyric acid (GABA) and glutamate in SNc, subsequently resulting in excitatory/inhibitory imbalance and locomotor deficits. Consequently, in vivo calcium imaging and interventions of neurotransmitter antagonists demonstrated that GABA accumulation mediated movement deficits of mice. Furthermore, 1 h/day intermittent astrocytic mitochondrial depolarization for 2 weeks triggered spontaneous locomotor dysfunction, α-synuclein aggregation, and the loss of DA neurons, suggesting that astrocytic mitochondrial depolarization was sufficient to induce a PD-like phenotype. In summary, our findings suggest the maintenance of proper astrocytic mitochondrial function and the reinstatement of a balanced neurotransmitter profile may provide a new angle for mitigating neuronal dysfunction during the initial phases of PD.

Transcriptional factor MdESE3 controls fruit acidity by activating genes regulating malic acid content in apple.

Acidity is a key factor controlling fruit flavor and quality. In a previous study, combined transcriptome and methylation analyses identified a P3A-type ATPase from apple (Malus domestica), MdMa11, which regulates vacuolar pH when expressed in Nicotiana benthamiana leaves. In this study, the role of MdMa11 in controlling fruit acidity was verified in apple calli, fruits, and plantlets. In addition, we isolated an AP2 domain-containing transcription factor, designated MdESE3, based on yeast one-hybrid (Y1H) screening using the MdMa11 promoter as bait. A subcellular localization assay indicated that MdESE3 localized to the nucleus. Analyses of transgenic apple calli, fruits, and plantlets, as well as tomatoes, demonstrated that MdESE3 enhances fruit acidity and organic acid accumulation. Meanwhile, chromatin immunoprecipitation quantitative PCR (ChIP-qPCR), luciferase (LUC) transactivation assays, and GUS reporter assays indicated that MdESE3 could bind to the ethylene-responsive element (ERE; 5'-TTTAAAAT-3') upstream of the MdMa11 transcription start site, thereby activating its expression. Furthermore, MdtDT, MdDTC2, and MdMDH12 expression increased in apple fruits and plantlets overexpressing MdESE3 and decreased in apple fruits and plantlets where MdESE3 was silenced. The ERE was found in MdtDT and MdMDH12 promoters, but not in the MdDTC2 promoter. The Y1H, LUC transactivation assays, and GUS reporter assays indicated that MdESE3 could bind to the MdtDT and MdMDH12 promoters and activate their expression. Our findings provide valuable functional validation of MdESE3 and its role in the transcriptional regulation of MdMa11, MdtDT, and MdMDH12 and malic acid accumulation in apple.

Vegetation redistribution is predicted to intensify soil organic carbon loss under future climate changes on the Tibetan Plateau.

Vegetation redistribution may bring unexpected climate-soil carbon cycling in terrestrial biomes. However, whether and how vegetation redistribution alters the soil carbon pool under climate change is still poorly understood on the Tibetan Plateau. Here, we applied the G-Range model to simulate the cover of herbs, shrubs and trees, net primary productivity (NPP) and soil organic carbon density (SOCD) at the depth of 60 cm on Tibetan Plateau for the individual years 2020 and 2060, using climate projection for Representative Concentration Pathways (RCP) 4.5 and RCP8.5 scenarios with the RegCM4.6 model system. Vegetation redistribution was defined as the transitions in bare ground, herbs, shrubs and trees between 2020 and 2060, with approximately 57.9 % (RCP4.5) and 59 % (RCP8.5) of the area will redistribute vegetation over the whole Tibetan Plateau. The vegetation cover will increase by about 2.4 % (RCP4.5) and 1.9 % (RCP8.5), while the NPP and SOCD will decrease by about -14.3 g C m-2 yr-1 and -907 g C m-2 (RCP4.5), and -1.8 g C m-2 yr-1and -920 g C m-2 (RCP8.5). Shrubs and trees will expand in the east, and herbs will expand in the northwest part of the Plateau. These areas are projected to be hotspots with greater SOCD reduction in response to future climate change, and will include lower net plant carbon input due to the negative NPP. Our study indicates that the SOC pool will become a carbon source under increased air temperature and rainfall on the Tibetan Plateau by 2060, especially for the area with vegetation redistribution. These results revealed the potential risk of vegetation redistribution under climate change in alpine ecosystems, indicating the policymakers need to pay attention on the vegetation redistribution to mitigate the soil carbon emission and achieve the goal of carbon neutrality on the Tibetan Plateau.

Single-cell analyses reveal the metabolic heterogeneity and plasticity of the tumor microenvironment during head and neck squamous cell carcinoma progression.

Metabolic reprogramming is a hallmark of cancer. In addition to metabolic alterations in the tumor cells, multiple other metabolically active cell types in the tumor microenvironment (TME) contribute to the emergence of a tumor-specific metabolic milieu. Here, we defined the metabolic landscape of the TME during progression of head and neck squamous cell carcinoma (HNSCC) by performing single-cell RNA sequencing (scRNA-seq) on 26 human patient specimens, including normal tissue, pre-cancerous lesions, early-stage cancer, advanced-stage cancer, lymph node metastases, and recurrent tumors. The analysis revealed substantial heterogeneity at the transcriptional, developmental, metabolic, and functional levels in different cell types. SPP1+ macrophages were identified as a pro-tumor and pro-metastatic macrophage subtype with high fructose and mannose metabolism, which was further substantiated by integrative analysis and validation experiments. An inhibitor of fructose metabolism reduced the proportion of SPP1+ macrophages, reshaped the immunosuppressive TME, and suppressed tumor growth. In conclusion, this work delineated the metabolic landscape of HNSCC at a single-cell resolution and identified fructose metabolism as a key metabolic feature of a pro-tumor macrophage subpopulation.

Predicting slight freezing of gait in Parkinson's disease with anticipatory postural adjustments and limits of stability.

INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.

Effect of Aggregation Structure on Capacitive Energy Storage in Conducting Polymer Films.

Conducting polymers (CPs), a significant class of electrochemical capacitor electrode materials, exhibit exceptional capacitive energy storage performance in aqueous electrolytes. Current research primarily concentrates on enhancing the electrical conductivity and capacitive performance of CPs via molecular design and structural control. However, the absence of a comprehensive understanding of the impact of molecular chain spatial order on ion/electron transport and capacitive performance impedes the development and optimization of advanced electrode materials. Here, a solvent treatment strategy is employed to modulate the molecular chain spatial order of PEDOT : PSS films. The results of electrochemical performance tests and Grazing Incidence Wide Angle X-ray Scattering (GIWAXS) show that Poly(3,4-ethylenedioxythiophene) : poly(styrenesulfonic acid) (PEDOT : PSS) films with both face-on and edge-on orientations exhibit exceptional electronic conductivity and ion diffusion efficiency, with capacitive performance 1.33 times higher than that of PEDOT : PSS films with only edge-on orientation. Consequently, molecular chain orientations conducive to charge transport not only enhance inter-chain coupling, but also effectively reduce ion transport resistance, enabling efficient capacitive energy storage. This research provides novel insights for the design and development of higher performance CPs-based electrode materials.

Application of the ankle pump method in a sitting position to evaluate calf perforating veins by color Doppler ultrasound.

OBJECTIVE: We investigated the feasibility and efficacy of assessing calf perforating veins (PVs) using the ankle pump in a sitting position (AP-sit) method by color Doppler ultrasound. METHODS: We performed a multicenter prospective clinical trial between November 2022 and October 2023. Eligible patients with chronic venous disease and healthy controls were enrolled. The calf PVs were assessed using three different methods: manual compression in a standing position, manual compression in a sitting position, and AP-sit method. The reflux durations and detection rate of incompetent PVs (IPVs) were compared among the three methods. The number and diameter of calf PVs and distribution of IPVs were analyzed. RESULTS: A total of 50 patients with chronic venous disease and 50 healthy controls were included. There were 173 calves analyzed, including 97 healthy calves and 76 calves with chronic venous disease. The number of PVs per calf was higher in the diseased calves (median, 7.0; interquartile range [IQR], 6.0-8.0) than in the healthy calves (median, 5.0; IQR, 3.0-6.0; P < .001). The diameter of IPVs (median, 2.3 mm; IQR, 2.0-3.1 mm) was larger than that of competent PVs (median, 1.4 mm; IQR, 1.2-1.7 mm). Most of the IPVs (78.8%) were located in the medial and posterior middle of the calf. The reflux duration induced by the AP-sit method was greater than that induced by the manual compression methods (P < .001). Although the AP-sit method had a higher detection rate (92.0%) of IPVs than the manual compression methods (71.7% and 74.3% for standing and sitting, respectively; P < .001), especially in the distal lower leg, the manual compression methods found IPVs not found using the AP-sit method. CONCLUSIONS: Diseased calves with chronic venous disease have more PVs than do healthy calves. IPVs are commonly larger than competent PVs, with most IPVs located in the medial and posterior middle of the calf. Most importantly, the AP-sit method provides a convenient and effective approach for assessing the calf PVs, especially those located in the distal calf, as an alternative or complementary method to traditional manual compression, which is valuable in the daily practice of sonographers.

The role of peripheral inflammation-related biomarkers in distinguishing Parkinson's disease.

BACKGROUND: Peripheral inflammation plays a significant role in Parkinson's disease (PD). Conflicting studies on whether inflammatory indicators in blood could serve as biomarkers to distinguish PD. OBJECTIVE: Include a wider range of biomarkers and control confounding factors to comprehensively evaluate the value of peripheral inflammation-related indicators. METHODS: A total of 80 PD patients were recruited and 80 one-to-one matched healthy controls (HCs). The levels of B-cell, T-cell, and natural killer (NK)-cell in blood were measured using flow cytometry. The levels of neurodegeneration-related proteins in serum were detected and clinical blood test results were collected. Multivariable logistic regression analysis was conducted to explore the role of significant variables in PD. Receiver operating characteristic curve analysis was performed to assess the potential value of these variables. RESULTS: Compared to HCs, PD patients showed lower levels of lymphocyte, B-cell, T-cell, high-density lipoprotein cholesterol (HDL-C) and lymphocyte-to-monocyte ratio, while the levels of neutrophil, NK-cell, ß-amyloid40, neurofilament light chain, neutrophil-to-lymphocyte ratio, and neutrophil-to-HDL-C ratio (NHR) were increased. A higher B-cell count was associated with a lower risk of PD, while higher levels of NK-cell and NHR were associated with a higher risk of PD. B-cell, NK-cell and NHR have potential value in distinguishing PD from non-PD. B-cell and NHR levels were significantly correlated with PD dyskinesia scores. CONCLUSIONS: B-cell, NK-cell, and NHR may potentially contribute to distinguishing PD patients from HCs. There could be a correlation between the number of B-cell, the level of NHR, and the severity of PD dyskinesia.

Study on lattice dynamics and thermal conductivity of fluorite AF2 (A = Ca, Sr, Ba) based on first principles calculations.

Fluorite materials have received particular attention in electron optics due to their favorable optical properties. However, further exploration of these materials in the thermoelectric (TE) field is hampered by the lack of studies on their lattice thermal transport properties. In this work, we use first-principles calculations, combined with self-consistent phonon theory, compressive sensing lattice dynamics and the Boltzmann transport equation, to study the microscopic mechanism of lattice thermal transport properties in AF2 (A = Ca, Sr, Ba) with a fluorite structure. We investigate the effects of three-phonon and four-phonon scattering and quartic anharmonic renormalization of phonon frequencies on this system. The results show that the bonding strength of atoms A (Ca, Sr, and Ba) plays an important role in the thermal transport process, and the third-order anharmonicity also plays an important role in this system. Meanwhile, the role of the quartic anharmonicity cannot be ignored. Our findings not only fill in the gaps in the study of lattice thermal transport of fluorite materials, but also deepen the comprehensive understanding of the high κL value of fluorite materials.

Identification of testis development-related genes by combining Iso-Seq and RNA-Seq in Zeugodacus tau.

Introduction: Zeugodacus tau (Walker) is an invasive pest. An effective method to control this pest is the sterile insect technique (SIT). To better apply this technique, it is necessary to understand testis development progression. Methods: Differentially expressed genes (DEGs) during testis development were analyzed by PacBio Iso-Seq and RNA-seq. Results: RNA-Seq library of Z. tau testes on day 1, 6, and 11 post eclosion were constructed. We identified 755 and 865 differentially expressed genes in the comparisons of T6 (testes on day 6) vs. T1 and T11 vs. T1, respectively. The KEGG pathway analysis showed that the DEGs were significantly enriched in retinol metabolism, vitamin B6 metabolism, and ascorbate and aldarate metabolism pathways. Knockdown of retinol dehydrogenase 12-like (rdh12-like), pyridoxal kinase (pdxk) and regucalcin (rgn), the representative gene in each of the above 3 pathways, reduced the hatching rate of Z. tau offspring. In addition, we identified 107 Drosophila spermatogenesis-related orthologous genes in Z. tau, of which innexin 2 (inx2) exhibited significantly up-regulated expression throughout testis development, and the knockdown of this gene reduced offspring hatching rate. Discussion: Our data indicated that rdh12-like, pdxk, rgn, and inx2 genes were related to testis development, and they were conserved in tephritid species. These results suggested that this gene might have the same function in tephritid. The findings provide an insight into testis development and spermatogenesis in tephritid species.

Carbazole and Quinazolinone Derivatives from a Fluoride-Tolerant Streptomyces Strain OUCMDZ-5511.

Six new 9H-carbazole derivatives (1-6) and nine previously reported compounds (7-15) were isolated from a fermented solid medium of the Thailand mangrove-derived Streptomyces strain, OUCMDZ-5511, under fluoride stress. Compounds 2-5, 12, and 15 were exclusively present in the fluoride-supplemented fermentation medium, while compounds 7-9, 13, and 14 were newly discovered natural products. The molecular structures of the compounds were identified by a spectroscopic analysis. The new compound 2 displayed antiquorum sensing activity against Chromobacterium violaceum ATCC 12472 by reducing the violacein production and inhibiting the biofilm formation in a concentration-dependent manner. The study revealed that compound 2 could be a novel potential inhibitor of quorum sensing.

Transcriptomic responses of cumulus granulosa cells to SARS-CoV-2 infection during controlled ovarian stimulation.

Cumulus granulosa cells (CGCs) play a crucial role in follicular development, but so far, no research has explored the impact of SARS-CoV-2 infection on ovarian function from the perspective of CGCs. In the present study, we compared the cycle outcomes between infected and uninfected female patients undergoing controlled ovarian stimulation, performed bulk RNA-sequencing of collected CGCs, and used bioinformatic methods to explore transcriptomic changes. The results showed that women with SARS-CoV-2 infection during stimulation had significantly lower number of oocytes retrieved and follicle-oocyte index, while subsequent fertilization and embryo development were similar. CGCs were not directly infected by SARS-CoV-2, but exhibited dramatic differences in gene expression (156 up-regulated and 65 down-regulated). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated a high enrichment in antiviral, immune and inflammatory responses with necroptosis. In addition, the pathways related to telomere organization and double strand break repair were significantly affected by infection in gene set enrichment analysis. Further weighted gene co-expression network analysis identified a key module associated with ovarian response traits, which was mainly enriched as a decrease of leukocyte chemotaxis and migration in CGCs. For the first time, our study describes how SARS-CoV-2 infection indirectly affects CGCs at the transcriptional level, which may impair oocyte-CGC crosstalk and consequently lead to poor ovarian response during fertility treatment.

Generation of induced pluripotent stem cells (ZZUCSBi001-A) from skin fibroblasts of a healthy donor.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.