Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

Establishment of a novel microfluidic co-culture system for simultaneous analysis of multiple indicators of gefitinib sensitivity in colorectal cancer cells.

The therapeutic effect of gefitinib on colorectal cancer (CRC) is unclear, but it has been reported that stromal cells in the tumor microenvironment may have an impact on drug sensitivity. Herein, we established a microfluidic co-culture system and explored the sensitivity of CRC cells co-cultured with cancer-associated fibroblasts (CAFs) to gefitinib. The system consisted of a multichannel chip and a Petri dish. The chambers in the chip and dish were designed to continuously supply nutrients for long-term cell survival and create chemokine gradients for driving cell invasion without any external equipment. Using this system, the proliferation and invasiveness of cells were simultaneously evaluated by quantifying the area of cells and the migration distance of cells. In addition, the system combined with live cell workstation could evaluate the dynamic drug response of co-cultured cells and track individual cell trajectories in real-time. When CRC cells were co-cultured with CAFs, CAFs promoted CRC cell proliferation and invasion and reduced the sensitivity of cells to gefitinib through the exosomes secreted by CAFs. Furthermore, the cells that migrated out of the chip were collected, and EMT-related markers were determined by immunofluorescent and western blot assays. The results demonstrated that CAFs affected the response of CRC cells to gefitinib by inducing EMT, providing new ideas for further research on the resistance mechanism of gefitinib. This suggests that targeting CAFs or exosomes might be a new approach to enhance CRC sensitivity to gefitinib, and our system could be a novel platform for investigating the crosstalk between tumor cells and CAFs and understanding multiple biological changes of the tumor cells in the tumor microenvironment.

Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Perioperative immunotherapy for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological subtype and accounts for 85% of esophageal cancer cases worldwide. Traditional treatment for ESCC involves chemotherapy, radiotherapy, and surgery. However, the overall prognosis remains unfavorable. Recently, immune checkpoint blockade (ICB) therapy using anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) antibodies have not only achieved remarkable benefits in the clinical management of ESCC but have also completely changed the treatment approach for this cancer. In just a few years, ICB therapy has rapidly advanced and been added to standard first-line treatment regimen in patients with ESCC. However, preoperative immunotherapy is yet to be approved. In this review, we summarize the ICB antibodies commonly used in clinical immunotherapy of ESCC, and discuss the advances of immunotherapy combined with chemotherapy and radiotherapy in the perioperative treatment of ESCC, aiming to provide reference for clinical management of ESCC patients across the whole course of treatment.

Discovery of potent small molecule inhibitors of histone lysine methyltransferase NSDs.

Nuclear receptor binding SET domain (NSD) proteins are a class of histone lysine methyltransferases and implicated in multiple cancer types with aberrant expression and involvement of cancer related signaling pathways. In this study, a series of small-molecule compounds including compound 2 and 3 are identified against the SET domain of NSDs through structure-based virtual screening. Our lead compound 3 exhibits potent inhibitory activities in vitro towards the NSD2-SET and NSD3-SET with an IC50 of 0.81 µM and 0.84 µM, respectively, and efficiently inhibits histone H3 lysine 36 dimethylation and decreases the expression of NSDs-targeted genes in non-small cell lung cancer cells at 100 nM. Compound 3 suppresses cell proliferation and reduces the clonogenicity in H460 and H1299 non-small cell lung cancer cells, and induces s-phase cell cycle arrest and apoptosis. These data establish our compounds as a valuable tool-kit for the study of the biological roles of NSDs in cancer.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Effects of water washing and KOH activation for upgrading microalgal torrefied biochar.

Torrefaction is an effective pathway for microalgal solid biofuel upgrading, and alkali metal activation is also an efficient method to enhance fuel properties. This study explores the comparison of torrefaction alone and KOH activation combined with torrefaction to determine a better operation for biochar production from the microalga Nannochloropsis Oceanica. The results indicate that the HHV ranges of KOH-activated biochar and unactivated biochar are 25.611-32.792 MJ·kg-1 and 25.024-26.389 MJ·kg-1, respectively. Furthermore, KOH-activated biochar is better than unactivated biochar, with less residue, broader pyrolysis and combustion temperature ranges, higher elemental carbon, and less combined carbon. Moreover, KOH-activated biochar is close to the unactivated one from the viewpoint of expense calculation and life cycle assessment and thus possesses a better comprehensive performance. Overall, KOH activation is an efficient method for upgrading microalgal solid biofuel. The results are conducive to exploring further modification of microalgal solid biofuel production with better properties, thus leading to a greener and more efficient approach for upgrading fuel performance.

Correlating the Photovoltaic Performance and Stability of the All-Small-Molecule Organic Solar Cells to Their Intermixed Phases Determined by Concentration-Dependent Ultraviolet-Visible Absorption Spectroscopy.

In addition to the donor-acceptor nano phases, the intermixed phase within the organic blends is crucial for the photovoltaic performance and stability of the bulk-heterojunction organic solar cells (OSCs). Here, the intermixed phase of a representative M-PhS:BTP-eC9 all-small-molecule organic solar cell was investigated by a concentration-dependent ultraviolet-visible (UV-vis) absorption spectroscopy method, where a shift of the absorption maximum wavelength was measured for the acceptor component with the increase of the acceptor concentration. The blend ratios of the acceptor to the donor in the intermixed phase, corresponding to the critical concentration for the formation of the acceptor nanophase (CAP), were determined to be 0.35, 0.20, and 0.15 for the as-cast, thermal annealing (TA), and the combined TA and solvent vapor annealing films. These results indicated that M-PhS and BTP-eC9 are kinetically well intermixed during spin coating, whereas TA and the following solvent annealing promote the crystallization of BTP-eC9 molecules out of the intermixed phase. The photovoltaic performance of the M-PhS:BTP-eC9 cells with different blend ratios was investigated. The formation of the BTP-eC9 nano phase in the blend film leads to stable VOC and fast increased JSC, which can be understood by the reduction of bimolecular charge recombination and the formation of electron transporting pathways within the photoactive layer. Similarly, the critical concentration for the formation of the donor phase was estimated to be 0.15 by measuring the stabilized VOC and increased JSC values of the cells with different donor blending ratios. More importantly, after a fast "burn-in" thermal degradation, the M-PhS:BTP-eC9 cell showed excellent thermal stability aging at 85 °C for over 1128 h, which is in good accordance with the unchanged intermixed phases measured by the UV-vis spectra of the annealed films. The current work demonstrates the feasibility of the spectroscopy method to investigate the intermixed phases for organic bulk-heterojunction solar cells and proves that all-small-molecule solar cells can be intrinsically very stable.

Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ). The polygenic effects on the neuroimaging alterations in DS still remain unknown. This study aims to calculate the polygenic risk scores for schizophrenia (PRS-SCZ) in DS, and further explores the potential associations with functional features of brain. PRS-SCZ was calculated according to the Whole Exome sequencing and Genome-wide association studies (GWAS). Resting-state fMRI, as well as biochemical features and neurocognitive data were obtained from 33 DS, 47 NDS and 41 HCs, and association studies of genetic risk with neuroimaging were performed in this sample. The analyses of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were performed to detect the functional alterations between DS and NDS. In addition, correlation analysis was used to investigate the relationships between functional features (ALFF, ReHo, FC) and PRS-SCZ. The PRS-SCZ of DS was significantly lower than that in NDS and HC. Compared to NDS, there was a significant increase in the ALFF of left inferior temporal gyrus (ITG.L) and left inferior frontal gyrus (IFG.L) and a significant decrease in the ALFF of right precuneus (PCUN.R) and ReHo of right middle frontal gyrus (MFG.R) in DS. FCs were widely changed between DS and NDS, mainly concentrated in default mode network, including ITG, PCUN and angular gyrus (ANG). Correlation analysis revealed that the ALFF of left ITG, the ReHo of right middle frontal gyrus, the FC value between insula and ANG, left ITG and right corpus callosum, left ITG and right PCUN, as well as the scores of Trail Making Test-B, were associated with PRS-SCZ in DS. The present study demonstrated the differential polygenic effects on functional changes of brain in DS and NDS, providing a potential neuroimaging-genetic perspective for the pathogenesis of schizophrenia.

Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell.

The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449-3500, 2278-3257 and 1621-2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma.

BACKGROUND: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet. AIM: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD. METHODS: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels. CONCLUSION: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Construction of nano-silica particle clusters and their effects on the shear thickening properties of liquids.

It is of great research significance to prepare a new shear thickening fluid (STF) with a simple process, remarkable thickening effect and excellent impact resistance from the properties of the particles. Inspired by the shear thickening mechanism, nano-silica particle clusters (SPC) with different morphological structures were prepared by the reaction of amino-modified silica with polyethylene glycol diglycidyl ether (PEGDGE), and the structure models of particle clusters were designed through theoretical analysis. The structure of SPC was affected by the degree of amination modification and the molecular weight of PEGDGE, which was analyzed by DLS and TEM. The shear thickening behavior of the fluid was evaluated by steady-state rheology and dynamic-state rheology analysis. The shear thickening behavior of the fluid composed of SPC also changed greatly with the influence of the degree of amination modification and the molecular weight of PEGDGE. In addition, compared with the STF contained original silica, the STF contained SPC could produce a faster and stronger shear thickening response. Therefore, silica particle clusters are not only a promising candidate for the preparation of high-performance shear thickening fluids, but can also be better applied to industrial and scientific fields such as impact protection and shock absorption.

Inhibiting miR-33b-5p Enhances Chemoresistance in Lung Adenocarcinoma by Targeting YWHAH to Regulate Epithelial-mesenchymal Transition.

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) is the most malignant type of lung cancer, whose clinical treatment is seriously hindered by chemoresistance. Numerous reports have demonstrated that miR-33b-5p plays an essential role in alleviating the chemoresistance of multiple cancers, but there are currently no reports about the effects of miR-33b-5p on the chemoresistance in LUAD. Our study aimed to investigate the impacts of miR-33b-5p on the chemoresistance in LUAD and the underlying mechanism. MATERIALS AND METHODS: Bioinformatics analyses were employed to investigate the relation between miR-33b-5p and YWHAH. The MTT assay and flow cytometry were respectively adopted to determine cell viability and apoptosis. A transwell assay was employed to evaluate cellular invasion and migration. qRT-PCR and western blotting were respectively employed to detect the gene expression of miR-33b-5p and the protein expression of YWHAH, MMP2, Snail, and Zeb1. RESULTS: Three bioinformatics analysis approaches predicted that YWHAH was the underlying targeted gene of miR-33b-5p and revealed the associated mechanisms. The concentration of paclitaxel (TAX) and cisplatin (DDP) needed to induce chemoresistance of LUAD cells was determined as 100 µM. Migration and invasion, as well as protein expression of YWHAH, MMP2, MMP8, Snail and Zeb1 were increased, but the apoptosis and levels of miR-33b-5p were reduced in A549 cells with chemoresistance. Knockdown of miR-33b-5p exerted the same effects produced by chemoresistance, but additional knockdown of YWHAH reversed the effects generated by inhibiting miR-33b-5p. CONCLUSION: Our study confirmed that knockdown of miR-33b-5p aggravated chemoresistance in LUAD via targeting YWHAH to regulate EMT.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of in vivo assays.

As one representative of nanometal oxides, titanium dioxide nanoparticles (TiO2-NPs) have been widely used, particularly in the food industry. The genotoxicity of TiO2-NPs has attracted great attention over the years. This study was undertaken to investigate the chromosome and DNA damage effects of TiO2-NPs (0, 50, 150, and 500 mg/kg BW) using rodent models. After a comprehensive characterization, we conducted a standard battery of in vivo genotoxicity tests, including the chromosomal aberration test (CA), micronucleus (MN) test, and the comet test. The results of all these tests were negative. There were no structural or numerical chromosomal abnormalities in mice bone marrow cells, no increase in the frequency of micronucleated polychromatic erythrocytes in mice bone marrow cells, and no elevation in % tail DNA in rat hepatocytes. This indicated that TiO2-NPs did not cause chromosomal damage or have a direct impact on DNA. These findings suggested that TiO2-NPs did not exhibit genotoxicity and provided valuable data for risk assessment purposes.

Thermal-Induced Performance Decay of the State-of-the-Art Polymer: Non-Fullerene Solar Cells and the Method of Suppression.

Improving thermal stability is of great importance for the industrialization of polymer solar cells (PSC). In this paper, we systematically investigated the high-temperature thermal annealing effect on the device performance of the state-of-the-art polymer:non-fullerene (PM6:Y6) solar cells with an inverted structure. Results revealed that the overall performance decay (19% decrease) was mainly due to the fast open-circuit voltage (VOC, 10% decrease) and fill factor (FF, 10% decrease) decays whereas short circuit current (JSC) was relatively stable upon annealing at 150 °C (0.5% decrease). Pre-annealing on the ZnO/PM6:Y6 at 150 °C before the completion of cell fabrication resulted in a 1.7% performance decrease, while annealing on the ZnO/PM6:Y6/MoO3 films led to a 10.5% performance decay, indicating that the degradation at the PM6:Y6/MoO3 interface is the main reason for the overall performance decay. The increased ideality factor and reduced built-in potential confirmed by dark J - V curve analysis further confirmed the increased interfacial charge recombination after thermal annealing. The interaction of PM6:Y6 and MoO3 was proved by UV-Vis absorption and XPS measurements. Such deep chemical doping of PM6:Y6 led to unfavorable band alignment at the interface, which led to increased surface charge recombination and reduced built-in potential of the cells after thermal annealing. Inserting a thin C60 layer between the PM6:Y6 and MoO3 significantly improved the cells' thermal stability, and less than 2% decay was measured for the optimized cell with 3 nm C60.

A Novel Acoustic Evaluation Method for the Diagnosis of Adductor Spasmodic Dysphonia.

INTRODUCTION: Adductor spasmodic dysphonia (ADSD) is characterized by involuntary laryngeal muscle spasms. Due to the lack of a quantitative evaluation method, most measurements have demonstrated difficulty in validity and reliability for diagnosing ADSD. This study aimed to establish a novel indicator for ADSD and determine its diagnostic effects. METHODS: We investigated 98 voice samples from 49 patients with ADSD and 49 healthy subjects. A sustained vowel was recorded by a high-definition audio recorder. Voice samples underwent regular acoustic evaluation and a novel global dimension method. Global dimension (GD), Jitter, Shimmer, HNR, Frequency shift, and CPPS were measured for both groups. RESULTS: Statistical analysis revealed that the global dimension method effectively differentiated ADSD patients from healthy subjects (P<0.001, D'>0.8). Subsequent multiclass receiver operating characteristic analysis demonstrated that GD possessed the most significant classification accuracy (AUC = 0.988) compared with other acoustic parameters. CONCLUSION: GD was an effective metric for objective differentiation between ADSD patients and healthy subjects. This metric could assist clinicians in the diagnosis of ADSD patients.

The role of the gut microbiome in weight-gain in schizophrenia patients treated with atypical antipsychotics: Evidence based on altered composition and function in a cross-sectional study.

OBJECTIVES: We aimed to explore the interconnection between the weight-gain in schizophrenia patients with atypical antipsychotic treatment and gut microbiome. METHODS: This study employed a cross-sectional design, encompassing a total of 88 schizophrenia patients with long-term atypical antipsychotic treatment. The 16S rRNA gene sequencing was used to identify gut microbiome contents. RESULTS: No significant differences in alpha diversity between normal-weight and overweight schizophrenia treated with atypical antipsychotics. The beta diversity analysis showed that overweight patients clustered tightly while normal-weight patients clustered widely. For taxonomic composition, overweight patients had a lower relative abundance in Porphyromonadaceae at family level and Butyrivibrio at genus level, but higher relative abundance in Ruminococcus2 and Clostridium_XIVa at genus level than normal-weight patients. Function prediction revelated that four pathways (including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection and Meiosis-yeast) were significantly different between groups. Correlation analysis indicated that Klebsiella, Butyrivibrio, Unassigned, Methanosphaera, Holdemania, Anaerotruncus were negatively, while Veillonella was positively correlated with BMI in patients. CONCLUSION: Our findings offer evidence that perturbations in the gut microbiome composition, encompassing taxa such as Porphyromonadaceae, Butyrivibrio, Ruminococcus2, and Clostridium_XIVa, in conjunction with distinct functional pathways including Cell cycle, Non-homologous end-joining, Vibrio cholerae infection, and Meiosis-yeast, might contribute to the weight-gain in schizophrenia treated with atypical antipsychotics.