Titanium dioxide nanoparticles Disrupt ultrastructure and function of Rat thyroid tissue via oxidative stress.

Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.

Liquid-Phase Exfoliation of 3D Metal-Organic Frameworks into Nanosheets.

Traditionally, the acquisition of 2D materials involved the exfoliation of layered crystals. However, the anisotropic bonding arrangements within 3D crystals indicate they are mechanically reminiscent of 2D counterparts and could also be exfoliated into nanosheets. This report delineates the preparation of 2D nanosheets from six representative 3D metal-organic frameworks (MOFs) through liquid-phase exfoliation. Notably, the cleavage planes of exfoliated nanosheets align perpendicular to the direction of the minimum elastic modulus (Emin) within the pristine 3D frameworks. The findings suggest that the in-plane and out-of-plane bonding forces of the exfoliated nanosheets can be correlated with the maximum elastic modulus (Emax) and Emin of the 3D frameworks, respectively. Emax influences the ease of cleaving adjacent layers, while Emin governs the ability to resist cracking of layers. Hence, a combination of large Emax and small Emin indicates an efficient exfoliation process, and vice versa. The ratio of Emax/Emin, denoted as Amax/min, is adopted as a universal index to quantify the ease of mechanical exfoliation for 3D MOFs. This ratio, readily accessible through mechanical experiments and computation, serves as a valuable metric for selecting appropriate exfoliation methods to produce surfactant-free 2D nanosheets from various 3D materials.

The prevalence, diagnostic accuracy and genotype-phenotype correlation of GNAS mutations in fibrous dysplasia: a meta-analysis.

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.

Detecting biomarkers by dynamic nuclear polarization enhanced magnetic resonance.

Hyperpolarization stands out as a technique capable of significantly enhancing the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Dynamic nuclear polarization (DNP), among various hyperpolarization methods, has gained prominence for its efficacy in real-time monitoring of metabolism and physiology. By administering a hyperpolarized substrate through dissolution DNP (dDNP), the biodistribution and metabolic changes of the DNP agent can be visualized spatiotemporally. This approach proves to be a distinctive and invaluable tool for non-invasively studying cellular metabolism in vivo, particularly in animal models. Biomarkers play a pivotal role in influencing the growth and metastasis of tumor cells by closely interacting with them, and accordingly detecting pathological alterations of these biomarkers is crucial for disease diagnosis and therapy. In recent years, a range of hyperpolarized DNP molecular bioresponsive agents utilizing various nuclei, such as 13C, 15N, 31P, 89Y, etc., have been developed. In this context, we explore how these magnetic resonance signals of nuclear spins enhanced by DNP respond to biomarkers, including pH, metal ions, enzymes, or redox processes. This review aims to offer insights into the design principles of responsive DNP agents, target selection, and the mechanisms of action for imaging. Such discussions aim to propel the future development and application of DNP-based biomedical imaging agents.

LcINH1 as an inhibitor of cell wall invertase LcCWIN5 regulates early seed development in Litchi chinensis Sonn.

Sugar signal mediated by Cell wall invertase (CWIN) plays a central role in seed development. In higher plants, invertase inhibitors (INHs) suppress CWIN activities at a post-translational level. In Litchi chinensis cultivar 'Nuomici', impaired CWIN expression is associated with seed abortion. Here, the expression of LcINH1 was significantly higher in the funicle of seed-aborting cultivar 'Nuomici' than big-seeded cultivar 'Heiye'. Promoter analyses found LcINH1 contained a 404 bp repeat fragment with an endosperm regulatory element of Skn-1_motif. LcINH1 and LcCWIN2/5 were located in plasma membrane. LcINH1 was able to interact with LcCWIN5, but not with LcCWIN2. In vitro enzyme activity assay demonstrated that LcINH1 could inhibit CWIN activity. Silencing LcINH1 in 'Nuomici' resulted in normal seed development, paralleled increased CWIN activities and glucose levels. Transcriptome analysis identified 1079 differentially expressed genes (DEGs) in LcINH1-silenced fruits. KEGG analysis showed significant enrichment of DEGs in pathways related to transporters and plant hormone signal transduction. Weighted gene co-expression network analysis indicated that the turquoise module was highly correlated with fructose content, and LcSWEET3b was closely associated with early seed development. These findings suggest that LcINH1 regulate LcCWIN5 activity at the post-translational level to alter sucrose metabolism, thereby affecting early seed development in litchi.

Nitrate Inhibits Nodule Nitrogen Fixation by Accumulating Ureide in Soybean Plants.

The mechanism by which nitrate inhibits nitrogen fixation in soybean (Glycine max L.) is not fully understood. Accumulation of ureide in soybean plant tissues may regulate the nitrogen fixation capacity through a feedback pathway. In this study, unilaterally nodulated dual-root soybeans prepared by grafting were grown in sand culture. They were subjected to the removal of the nodulated side roots, and were given either nitrate supply or no supply to the non-nodulated side roots for 3 days (experiment I). Additionally, they received nitrate supply to the non-nodulated side roots for 1-14 days (experiment II). The results showed that nitrate supply increased the levels of asparagine and ureide in soybean shoots (Experiment I). In Experiment II, nodule dry weight, nodule number, nodule nitrogenase activity, and nodule urate oxidase activity decreased significantly after 3, 7, and 14 days of nitrate supply. Ureide content in the shoots and nodules increased after 1, 3, and 7 days of nitrate supply, but decreased after 14 days of nitrate supply. There was a significant positive correlation between urate oxidase activity and nitrogenase activity. Hence, we deduced that nitrate supply increased the asparagine content in soybean shoots, likely inhibiting ureide degradation, which induced the accumulation of ureide in soybean shoots and nodules, and, in turn, feedback inhibited the nodule nitrogen fixation. In addition, urate oxidase activity can be used to assess the nitrogen fixation capacity of nodules.

Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Deciphering the molecular nexus between Omicron infection and acute kidney injury: a bioinformatics approach.

Background: The ongoing global health crisis of COVID-19, and particularly the challenges posed by recurrent infections of the Omicron variant, have significantly strained healthcare systems worldwide. There is a growing body of evidence indicating an increased susceptibility to Omicron infection in patients suffering from Acute Kidney Injury (AKI). However, the intricate molecular interplay between AKI and Omicron variant of COVID-19 remains largely enigmatic. Methods: This study employed a comprehensive analysis of human RNA sequencing (RNA-seq) and microarray datasets to identify differentially expressed genes (DEGs) associated with Omicron infection in the context of AKI. We engaged in functional enrichment assessments, an examination of Protein-Protein Interaction (PPI) networks, and advanced network analysis to elucidate the cellular signaling pathways involved, identify critical hub genes, and determine the relevant controlling transcription factors and microRNAs. Additionally, we explored protein-drug interactions to highlight potential pharmacological interventions. Results: Our investigation revealed significant DEGs and cellular signaling pathways implicated in both Omicron infection and AKI. We identified pivotal hub genes, including EIF2AK2, PLSCR1, GBP1, TNFSF10, C1QB, and BST2, and their associated regulatory transcription factors and microRNAs. Notably, in the murine AKI model, there was a marked reduction in EIF2AK2 expression, in contrast to significant elevations in PLSCR1, C1QB, and BST2. EIF2AK2 exhibited an inverse relationship with the primary AKI mediator, Kim-1, whereas PLSCR1 and C1QB demonstrated strong positive correlations with it. Moreover, we identified potential therapeutic agents such as Suloctidil, Apocarotenal, 3'-Azido-3'-deoxythymidine, among others. Our findings also highlighted a correlation between the identified hub genes and diseases like myocardial ischemia, schizophrenia, and liver cirrhosis. To further validate the credibility of our data, we employed an independent validation dataset to verify the hub genes. Notably, the expression patterns of PLSCR1, GBP1, BST2, and C1QB were consistent with our research findings, reaffirming the reliability of our results. Conclusion: Our bioinformatics analysis has provided initial insights into the shared genetic landscape between Omicron COVID-19 infections and AKI, identifying potential therapeutic targets and drugs. This preliminary investigation lays the foundation for further research, with the hope of contributing to the development of innovative treatment strategies for these complex medical conditions.

Effect of different endometrial preparation methods on pregnancy outcome of FET in women with a normal menstrual cycle.

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

Emergence of mcr-4.3 genes in a novel Shewanella specie isolated from the Arctic environment.

Mobile colistin resistance (mcr) genes are pivotal contributors to last-line of antimicrobial resistance in human infections. Shewanella, historically recognized as a natural environmental bacterium with metal reduction capabilities, recently has been observed in clinical settings. However, limited knowledge has been explored on genetic differences between strains from non-clinical and clinical strains. In this study, we conducted the whole genome sequencing on six Arctic strains, illustrated the phylogenetic relationships on published 393 Shewanella strains that categorized the genus into four lineages (L1 to L4). Over 86.4% of clinical strain group (CG) strains belonged to L1 and L4, carrying mcr-4 genes and a complete metal-reduction pathways gene cluster. Remarkably, a novel Arctic Shewanella strain in L3, exhibits similar genetic characteristics with CG strains that carried both mcr-4 genes and a complete metal reduction pathway gene cluster. It raised concerns about the transmission ability from environment to clinic setting causing in the potential infections, and emphasized the need for monitoring the emerging strains with human infections.

Association of Vestibular Disorders and Cognitive Function: A Systematic Review.

OBJECTIVES: The purpose of this study is to consolidate and condense the available evidence about the potential association between vestibular diseases and cognitive impairment. DATA SOURCES AND METHODS: A systematic search was conducted on four English databases (PubMed, Embase, Web of Science, Cochrane Library) from the time of library construction to March 2024. The study incorporated various keywords such as "vestibular disorders," "vertigo," "dizziness," "Meniere's disease," "benign paroxysmal positional vertigo," "vestibular migraine," "vestibular neuritis," "labyrinthitis," "bilateral vestibular disease," as well as "cognitive function" and "cognitive dysfunction." A qualitative review was conducted to look for and assess pertinent studies. RESULTS: A total of 45 publications were incorporated, encompassing prevalent vestibular disorders, mostly targeting individuals in the middle-aged and older demographic. The findings indicate that individuals with vestibular disorders experience varying levels of cognitive impairment, which is evident in different aspects, with visuospatial cognitive deficits being more prominent. Furthermore, patients with chronic vestibular syndromes are more prone to cognitive dysfunction. Lastly, the hippocampus plays a crucial role in the intricate vestibular neural network. CONCLUSION: The findings of this comprehensive review indicate that vestibular disorders can result in impairments across various aspects of cognitive functioning, particularly in visuospatial cognition. The underlying mechanism may be associated with a decrease in the size of the hippocampus. Individuals suffering from chronic vestibular dysfunction exhibit a higher likelihood of experiencing cognitive deficits. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Flexible Asymmetric Supercapacitors Constructed by Reduced Graphene Oxide/MoO3 and MnO2 Electrochemically Deposited on Carbon Cloth.

A flexible asymmetric supercapacitor (ASC) is successfully developed by using the composite of MoO3 and graphene oxide (GO) electrochemically deposited on carbon cloth (CC) (MoO3/rGO/CC) as the cathode, the MnO2 deposited on CC (MnO2/CC) as the anode, and Na2SO4/polyvinyl alcohol (PVA) as the gel electrolyte. The results show that the introduction of the GO layer can remarkably increase the specific capacitance of MoO3 from 282.7 F g-1 to 341.0 F g-1. Furthermore, the combination of such good electrode materials and a neutral gel electrolyte renders the fabrication of high-performance ASC with a large operating potential difference of 1.6 V in a 0.5 mol L-1 Na2SO4 solution of water. Furthermore, the ASCs exhibit excellent cycle ability and the capacitance can maintain 87% of its initial value after 6000 cycles. The fact that a light-emitting diode can be lit up by the ASCs indicates the device's potential applications as an energy storage device. The encouraging results demonstrate a promising application of the composite of MoO3 and GO in energy storage devices.

Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication.

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.

Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation.

BACKGROUND: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGF-ß1-Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin (DCN), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-ß and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity. OBJECTIVE: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung. MATERIAL AND METHODS: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs-decorin, and decorin. Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted. RESULTS: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-ß levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis. CONCLUSION: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury.

Arabidopsis COP1 suppresses root hair development by targeting type I ACS proteins for ubiquitination and degradation.

Root hairs (RHs) are an innovation of vascular plants whose development is coordinated by endogenous and environmental cues, such as ethylene and light conditions. However, the potential crosstalk between ethylene and light conditions in RH development is unclear. We report that Arabidopsis constitutive photomorphogenic 1 (COP1) integrates ethylene and light signaling to mediate RH development. Darkness suppresses RH development largely through COP1. COP1 inhibits both cell fate determination of trichoblast and tip growth of RHs based on pharmacological, genetic, and physiological analyses. Indeed, COP1 interacts with and catalyzes the ubiquitination of ACS2 and ACS6. COP1- or darkness-promoted proteasome-dependent degradation of ACS2/6 leads to a low ethylene level in underground tissues. The negative role of COP1 in RH development by downregulating ethylene signaling may be coordinated with the positive role of COP1 in hypocotyl elongation by upregulating ethylene signaling, providing an evolutionary advantage for seedling fitness.

Protein S-acylation, a new panacea for plant fitness.

Protein S-acylation or palmitoylation is a reversible post-translational modification that influences many proteins encoded in plant genomes. Exciting progress in the past 3 years demonstrates that S-acylation modulates subcellular localization, interacting profiles, activity, or turnover of substrate proteins in plants, participating in developmental processes and responses to abiotic or biotic stresses. In this review, we summarize and discuss the role of S-acylation in the targeting of substrate proteins. We highlight complex roles of S-acylation in receptor signaling. We also point out that feedbacks of protein S-acyl transferase by signaling initiated from their substrate proteins may be a recurring theme. Finally, the reversibility of S-acylation makes it a rapid and efficient way to respond to environmental cues. Future efforts on exploring these important aspects of S-acylation will give a better understanding of how plants enhance their fitness under ever changing and often harsh environments.

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder characterized by social deficits and repetitive behavior. Gastrointestinal (GI) problems, such as constipation, diarrhea, and inflammatory bowel disease, commonly occur in patients with ASD. Previously, GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission. AIM: To explore whether GI problems in ASD are related to maternal intestinal inflammation and gut microbiota abnormalities. METHODS: An ASD rat model was developed using valproic acid (VPA). Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes. RESULTS: VPA exposure during pregnancy led to pathological maternal intestinal changes, resulting in alterations in maternal gut microbiota. Additionally, the levels of inflammatory factors also increased. Moreover, prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of inflammatory factors. CONCLUSION: GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality. Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Development and validation of dietary depression index in Chinese adults.

Objective: Previous studies have suggested diet was associated with depressive symptoms. We aimed to develop and validate Dietary Depression Index (DDI) based on dietary prediction of depression in a large Chinese cancer screening cohort.Methods: In the training set (n = 2729), we developed DDI by using intake of 20 food groups derived from a food frequency questionnaire to predict depression as assessed by Patient Health Questionnaire-9 based on the reduced rank regression method. Sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the performance of DDI in evaluating depression in the validation dataset (n = 1176).Results: Receiver operating characteristic analysis was constructed to determine the best cut-off value of DDI in predicting depression. In the study population, the DDI ranged from -3.126 to 1.810. The discriminative ability of DDI in predicting depression was good with the AUC of 0.799 overall, 0.794 in males and 0.808 in females. The best cut-off values of DDI for depression prediction were 0.204 overall, 0.330 in males and 0.034 in females. DDI was a validated method to assess the effects of diet on depression.Conclusion: Among individual food components in DDI, fermented vegetables, fresh vegetables, whole grains and onions were inversely associated, whereas legumes, pickled vegetables and rice were positively associated with depressive symptoms.