A modified glycosylase base editor without predictable DNA off-target effects.

Glycosylase base editor (GBE) can induce C-to-G transversion in mammalian cells, showing great promise for the treatment of human genetic disorders. However, the limited efficiency of transversion and the possibility of off-target effects caused by Cas9 restrict its potential clinical applications. In our recent study, we have successfully developed TaC9-CBE and TaC9-ABE by separating nCas9 and deaminase, which eliminates the Cas9-dependent DNA off-target effects without compromising editing efficiency. We developed a novel GBE called TaC9-GBEYE1, which utilizes the deaminase and UNG-nCas9 guided by TALE and sgRNA, respectively. TaC9-GBEYE1 showed comparable levels of on-target editing efficiency to traditional GBE at 19 target sites, without any off-target effects caused by Cas9 or TALE. The TaC9-GBEYE1 is a safe tool for gene therapy.

Salivary metabolomic identification of biomarker candidates for oral melanoma and oral squamous cell carcinoma in dogs.

BACKGROUND: Oral melanoma (OM) and oral squamous cell carcinoma (OSCC) are frequently diagnosed in dogs, presenting a challenge in distinguishing them from benign oral tumors (BN). Salivary metabolomic biomarkers offer a practical solution because of saliva's direct contact with tumors and the noninvasive nature of collection. OBJECTIVE: Assess the diversity and abundance of the salivary metabolome in dogs with BN, OM, and OSCC using amine/phenol submetabolome analysis and high-performance chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). ANIMALS: Study included 11 BN, 24 OM, 10 OSCC, and 20 healthy control dogs. METHODS: Case-control cross-sectional study was conducted to assess salivary submetabolic profiles in dogs with BN, OM, and OSCC and healthy dogs. Samples were labeled with 12C-dansyl chloride and analyzed using CIL LC-MS targeted to amine- and phenol-containing metabolites for amine/phenol submetabolome analysis. RESULTS: Distinct clusters and significant differences in metabolite concentrations were observed among the oral cancer, BN, and control groups. A total of 154 and 66 metabolites showed significantly altered concentrations, particularly in OM and OSCC, respectively, when compared with BN (Padj < .05). Potential metabolic biomarkers were identified for each cancer, including decreased concentrations of seryl-arginine and sarcosine in OSCC. Moreover, high-confidence putative metabolites were identified, including an increase in tryptophyl-threonine and a decrease in 1,2-dihydroxynapthalene-6-sulfonic acid and hydroxyprolyl-hydroxyproline for OM. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified high coverage of the amine/phenol submetabolome, including seryl-arginine, and sarcosine, in OSCC. Our findings emphasize the potential of these biomarkers for distinguishing between oral OSCC and BN in dogs.

The W-Plasty Serial Excision Method for Treating Medium Congenital Melanocytic Nevi: A Retrospective Analytical Study.

BACKGROUND: Serial excision remains the most commonly used surgical procedure for treating congenital melanocytic nevus (CMN). It is critical to remove as much of the lesion as possible with each procedure to reduce the number of procedures and to shorten the treatment duration. OBJECTIVE: To investigate the clinical efficacy of W-plasty serial excision for the repair of postoperative CMN defects. METHODS: A retrospective analysis of patients with medium CMN was conducted from April 2018 to March 2022. Treatment options were divided into elliptical serial excision (10 cases) and W-plasty serial excision (10 cases). RESULTS: Follow-up occurred over 6 months. The number of elliptical excision procedures was 2 to 4 (mean 2.9). The scar-to-lesion length ratio was 1.5 to 2.0 (mean 1.7). The mean Vancouver Scar Scale (VSS) score was 5.40 ± 0.42. The number of W-plasty excision procedures was 2 to 3 (mean 2.2). The scar-to-lesion length ratio was 1.2 to 1.5 (mean 1.4). The mean VSS score was 2.70 ± 0.26. W-plasty excision was superior to elliptical excision regarding the number of procedures and the effect on postoperative scars. CONCLUSION: W-plasty serial excision can be considered a suitable option for the excision of medium CMN, leading to excellent results.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

Effects of repetitive transcranial magnetic stimulation on fear of cancer recurrence and its underlying neuromechanism.

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment. Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated. Ethics and dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. Trial registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.

Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension.

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH. Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated. Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value. Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Deciphering Aphanomyces euteiches-pea-biocontrol bacterium interactions through untargeted metabolomics.

Aphanomyces euteiches causes root rot in pea, leading to significant yield losses. However, the metabolites involved in this pathosystem have not been thoroughly studied. This study aimed to fill this gap and explore mechanisms of bacterial suppression of A. euteiches via untargeted metabolomics using pea grown in a controlled environment. Chemical isotope labeling (CIL), followed by liquid chromatography-mass spectrometry (LC-MS), was used for metabolite separation and detection. Univariate and multivariate analyses showed clear separation of metabolites from pathogen-treated pea roots and roots from other treatments. A three-tier approach positively or putatively identified 5249 peak pairs or metabolites. Of these, 403 were positively identified in tier 1; 940 were putatively identified with high confidence in tier 2. There were substantial changes in amino acid pool, and fatty acid and phenylpropanoid pathway products. More metabolites, including salicylic and jasmonic acids, were upregulated than downregulated in A. euteiches-infected roots. 1-aminocyclopropane-1-carboxylic acid and 12-oxophytodienoic acid were upregulated in A. euteiches + bacterium-treated roots compared to A. euteiches-infected roots. A great number of metabolites were up- or down-regulated in response to A. euteiches infection compared with the control and A. euteiches + bacterium-treated plants. The results of this study could facilitate improved disease management.

A study on the correlations of PRL levels with anxiety, depression, sleep, and self-efficacy in patients with prolactinoma.

Purpose: The purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels. Methods: This retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups. Results: The median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P<0.05). Higher PRL levels were observed in the anxiety group compared to the non-anxiety group (P<0.001), in the insomnia group compared to the normal group (P<0.05), and in the low self-efficacy group compared to the medium and high self-efficacy groups (P<0.05). Conclusion: PRL levels in patients with prolactinoma are related to education level, tumor size, number of visits, anxiety, self-efficacy, and sleep but not depression. PRL levels were higher in patients with anxiety, low self-efficacy, and sleep disorders.

Identification of Novel Prognostic Biomarkers for Colorectal Cancer by Bioinformatics Analysis.

BACKGROUND/AIMS: Colorectal cancer (CRC) ranks third among malignancies in terms of global incidence and has a poor prognosis. The identification of effective diagnostic and prognostic biomarkers is critical for CRC treatment. This study intends to explore novel genes associated with CRC progression via bioinformatics analysis. MATERIALS AND METHODS: Dataset GSE184093 was selected from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between CRC and noncancerous specimens. Functional enrichment analyses were implemented for probing the biological functions of DEGs. Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter databases were employed for gene expression detection and survival analysis, respectively. Western blotting and real-time quantitative polymerase chain reaction were employed for detecting molecular protein and messenger RNA levels, respectively. Flow cytometry, Transwell, and CCK-8 assays were utilized for examining the effects of GBA2 and ST3GAL5 on CRC cell behaviors. RESULTS: There were 6464 DEGs identified, comprising 3005 downregulated DEGs (dDEGs) and 3459 upregulated DEGs (uDEGs). Six dDEGs were significantly associated with the prognoses of CRC patients, including PLCE1, PTGS1, AMT, ST8SIA1, ST3GAL5, and GBA2. Upregulating ST3GAL5 or GBA2 repressed the malignant behaviors of CRC cells. CONCLUSION: We identified 6 genes related to CRC progression, which could improve the disease prognosis and treatment.

Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer.

Purpose: To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). Methods: We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. Results: A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. Conclusion: The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

Introduction: A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed. Methods: We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC). Results: Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores. Conclusion: Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Transcriptome and biochemical analyses reveal phenolic compounds-mediated flavor differences in loquat (Eriobotrya japonica Lindl.) cultivars Chunhua No.1 and Dawuxing.

The novel loquat cultivar 'Chunhua No.1' (CH1) is a promising commercial cultivar. However, CH1 has texture characteristics different from those of common loquat, and its formation mechanism remains unclear. Here, we first identified the phenolic compounds of CH1 and its parent ('Dawuxing', DWX) and the effect on texture formation. The special presence of stone cells explained the flavor differences in CH1. Chlorogenic acid, neochlorogenic acid, and coniferyl alcohol were the main phenolic compounds in loquat, and the high content of coniferyl alcohol was a potential factor for the rough texture of CH1. Transcriptome reveals that phenylpropanoid metabolism was activated during CH1 fruit texture formation. Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 51 structural genes involved in phenylpropanoid biosynthesis, and Weighted Gene Co-expression Network Analysis (WGCNA) identified four structural genes and 88 transcription factors. These findings provide new insights into the phenolic metabolism and flavor formation of loquat fruit.

Effects of Thermal Exposure on the Microstructure and Mechanical Properties of a Ti-48Al-3Nb-1.5Ta Alloy via Powder Hot Isostatic Pressing.

Research on how thermal exposure affects the microstructure and mechanical properties of the Ti-48Al-3Nb-1.5Ta (at. %) alloy, which is prepared via powder hot isostatic pressing (P-HIP), is essential since this low-density alloy shows promise for use in high-temperature applications, particularly for aero-engines, which require long-term stable service. In this study, a P-HIP Ti-48Al-3Nb-1.5Ta (at. %) alloy was exposed to high temperatures for long durations. The phase, microstructure and mechanical properties of the P-HIP Ti-48Al-3Nb-1.5Ta alloy after thermal exposure under different conditions were analyzed using XRD, SEM, EBSD, EPMA, TEM, nanomechanical testing and tensile testing. The surface scale is composed of oxides and nitrides, primarily Al2O3, TiO2, and TiN, among which Al2O3 is preferentially generated and then covered by rapidly growing TiO2 as the thermal exposure duration increases. The nitrides appear later than the oxides and exist between the oxides and the substrate. With increasing exposure temperature and duration, the surface scale becomes more continuous, TiO2 particles grow larger, and the oxide layer thickens or even falls off. The addition of Ta and Nb can improve the oxidation resistance because Ta5+ and Nb5+ replace Ti4+ in the rutile lattice and weaken O diffusion. Compared with the P-HIP Ti-48Al-3Nb-1.5Ta alloy, after thermal exposure, the grain size does not increase significantly, and the γ phase increases slightly (by less than 3%) with the decomposition of the α2 phase. With increasing thermal exposure duration, the γ phase exhibits discontinuous coarsening (DC). Compared with the P-HIP Ti-48Al-3Nb-1.5Ta alloy, the hardness increases by about 2 GPa, the tensile strength increases by more than 50 MPa, and the fracture strain decreases by about 0.1% after thermal exposure. When the depth extends from the edge of the thermally exposed specimens, the hardness decreases overall.

Recent progress on bismuth-based light-triggered antibacterial nanocomposites: Synthesis, characterization, optical properties and bactericidal applications.

Bacterial infections pose a seriously threat to the safety of the environment and human health. In particular, the emergence of drug-resistant pathogens as a result of antibiotic abuse and high trauma risk has rendered conventional therapeutic techniques insufficient for treating infections by these so-called "superbugs". Therefore, there is an urgent need to develop highly efficient and environmentally-friendly antimicrobial agents. Bismuth-based nanomaterials with unique structures and physicochemical characteristics have attracted considerable attention as promising antimicrobial candidates, with many demonstratingoutstanding antibacterial effects upon being triggered by broad-spectrum light. These nanomaterials have also exhibited satisfactory energy band gaps and electronic density distribution with improved photonic properties for extensive and comprehensive applications after being modified through various engineering methods. This review summarizes the latest research progress made on bismuth-based nanomaterials with different morphologies, structures and compositions as well as the different methods used for their synthesis to meet their rapidly increasing demand, especially for antibacterial applications. Moreover, the future prospects and challenges regarding the application of these nanomaterials are discussed. The aim of this review is to stimulate interest in the development and experimental transformation of novel bismuth-based nanomaterials to expand the arsenal of effective antimicrobials.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Discovering the secondary metabolic potential of Saccharothrix.

Rare actinomycetes are highly valued as potential sources of novel bioactive secondary metabolites. Among these rare actinomycetes, the genus Saccharothrix is particularly noteworthy due to its ability to produce a diverse range of bioactive secondary metabolites. With the continuous sequencing of bacterial genomes and the rapid development of bioinformatics technologies, our knowledge of the secondary metabolic potential of Saccharothrix can become more comprehensive, but this space has not been reviewed or explored. This review presents a detailed overview of the chemical structures and bioactivities of 138 Saccharothrix-derived secondary metabolites, which are classified into five distinct groups based on their biosynthetic pathways. Furthermore, we delve into experimentally characterized biosynthetic pathways of nine bioactive metabolites. By utilizing a combination of cheminformatic and bioinformatic approaches, we attempted to establish connections between the metabolite families and the biosynthetic gene cluster families encoded by Saccharothrix strains. Our analysis provides a comprehensive perspective on the secondary metabolites that can be linked to corresponding BGCs and highlights the underexplored biosynthetic potential of Saccharothrix. This review also provides guidance for the targeted discovery and biosynthesis of novel natural products from Saccharothrix.