Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

PRMD: an integrated database for plant RNA modifications.

The scope and function of RNA modifications in model plant systems have been extensively studied, resulting in the identification of an increasing number of novel RNA modifications in recent years. Researchers have gradually revealed that RNA modifications, especially N6-methyladenosine (m6A), which is one of the most abundant and commonly studied RNA modifications in plants, have important roles in physiological and pathological processes. These modifications alter the structure of RNA, which affects its molecular complementarity and binding to specific proteins, thereby resulting in various of physiological effects. The increasing interest in plant RNA modifications has necessitated research into RNA modifications and associated datasets. However, there is a lack of a convenient and integrated database with comprehensive annotations and intuitive visualization of plant RNA modifications. Here, we developed the Plant RNA Modification Database (PRMD; http://bioinformatics.sc.cn/PRMD and http://rnainformatics.org.cn/PRMD) to facilitate RNA modification research. This database contains information regarding 20 plant species and provides an intuitive interface for displaying information. Moreover, PRMD offers multiple tools, including RMlevelDiff, RMplantVar, RNAmodNet and Blast (for functional analyses), and mRNAbrowse, RNAlollipop, JBrowse and Integrative Genomics Viewer (for displaying data). Furthermore, PRMD is freely available, making it useful for the rapid development and promotion of research on plant RNA modifications.

Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Ribo-uORF: a comprehensive data resource of upstream open reading frames (uORFs) based on ribosome profiling.

Upstream open reading frames (uORFs) are typically defined as translation sites located within the 5' untranslated region upstream of the main protein coding sequence (CDS) of messenger RNAs (mRNAs). Although uORFs are prevalent in eukaryotic mRNAs and modulate the translation of downstream CDSs, a comprehensive resource for uORFs is currently lacking. We developed Ribo-uORF (http://rnainformatics.org.cn/RiboUORF) to serve as a comprehensive functional resource for uORF analysis based on ribosome profiling (Ribo-seq) data. Ribo-uORF currently supports six species: human, mouse, rat, zebrafish, fruit fly, and worm. Ribo-uORF includes 501 554 actively translated uORFs and 107 914 upstream translation initiation sites (uTIS), which were identified from 1495 Ribo-seq and 77 quantitative translation initiation sequencing (QTI-seq) datasets, respectively. We also developed mRNAbrowse to visualize items such as uORFs, cis-regulatory elements, genetic variations, eQTLs, GWAS-based associations, RNA modifications, and RNA editing. Ribo-uORF provides a very intuitive web interface for conveniently browsing, searching, and visualizing uORF data. Finally, uORFscan and UTR5var were developed in Ribo-uORF to precisely identify uORFs and analyze the influence of genetic mutations on uORFs using user-uploaded datasets. Ribo-uORF should greatly facilitate studies of uORFs and their roles in mRNA translation and posttranscriptional control of gene expression.

A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.

BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models. METHODS: KTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC-MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR. RESULTS: KTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8+ T cells and innate immune cells. An intermittent dosing regimen of KTC1101 enhanced these effects. Notably, KTC1101 synergized with anti-PD-1 therapy, significantly boosting antitumor immunity and extending survival in preclinical models. CONCLUSION: KTC1101's dual mechanism of action-directly inhibiting tumor cell growth and dynamically enhancing the immune response- represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations.

A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Normal Values for Atrial Deformation Measured by Feature-Tracking Cardiac MRI: A Meta-Analysis.

BACKGROUND: A consensus on normal atrial deformation measurements by feature-tracking cardiac MRI remained absent. PURPOSE: Provide reference ranges for atrial strain parameters in normal subjects, evaluating the influence of field strength and analysis software on the measurements. STUDY TYPE: Meta-analysis. POPULATION: 2708 subjects from 42 studies undergoing cardiac MRI. ASSESSMENT: A systematic search was conducted from database (PubMed, Web of Science, ScienceDirect, and EMBASE) inception through August 2023. The random-effects model was used to pool the means of biatrial strain parameters. Heterogeneity and clinical variable effects were assessed. Strain measurements among different field strengths and analysis software were compared. STATISTICAL TESTS: The inverse-variance method, Cochrane Q statistic, and I2 value, meta-regression analysis, and ANOVA were used; P < 0.05 was considered statistically significant. RESULTS: The pooled means of left atrial (LA) total strain (εs), passive strain (εe), and active strain (εa) were 37.46%, 22.73%, and 16.24%, respectively, and the pooled means of LA total strain rate (SRs), passive strain rate (SRe), and active strain rate (SRa) were 1.66, -1.95, and -1.83, indicating significant heterogeneity. The pooled means of right atrial (RA) εs, εe, and εa were 44.87%, 26.05%, and 18.83%. RA SRs, SRe, and SRa were 1.66, -1.95, and -1.83, respectively. The meta-regression identified age as significantly associated with LA εs, εe and SRe, field strength was associated with LA SRa (all P < 0.05). ANOVA revealed differences in LA εa and SRa among different analysis software and in LA εs and all LA strain rates (all P < 0.05) among field strengths. No significant differences were identified in RA strain across analysis software (RA strain: P = 0.145-0.749; RA strain rates: P = 0.073-0.744) and field strengths (RA strain: P = 0.641-0.794; RA strain rates: P = 0.204-0.458). DATA CONCLUSION: This study demonstrated the pooled reference values of biatrial strain. Age, analysis software, and field strength were attributed to differences in LA strain, whereas RA strain showed consistency across different field strengths and analysis software. Limited study subjects may account for the absence of influence on RA strain. TECHNICAL EFFICACY: Stage 5.

MRI Assessment of Diastolic Dysfunction in People Living With the Human Immunodeficiency Virus: Correlation With Markers of Disease Activity.

BACKGROUND: Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. PURPOSE: To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. STUDY TYPE: Prospective. POPULATION: A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). FIELD STRENGTH/SEQUENCE: 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. ASSESSMENT: Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. STATISTICAL TESTS: Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). RESULTS: PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (ß = 0.51). CONCLUSION: LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice.

Growing evidence has demonstrated that cold and humid environmental stress triggers gastrointestinal (GI) disorders. In this study, we explored the effects of intestinal microbiota homeostasis on the intestinal mucus barrier and GI disorders by cold and humid environmental stress. Moreover, the inner link between the intestinal mucosal microbiota and metabolites in mice with cold and humid environmental stress was interpreted by integrative analysis of PacBio HiFi sequencing microbial genomics and targeted metabolomics. In the current study, we found (1) after the cold and wet cold and humid environmental stress intervened in the intestinal microbiota disorder and homeostasis mice respectively, the bacterial culturing and fluorescein diacetate (FDA) microbial activity detection of intestinal microbiota including feces, intestinal contents, and intestinal mucosa suggested that the cold and humid environmental stress decreased the colony of culturable bacteria and microbial activity, in which intestinal microbiota disorder aggravated the injury of the intestinal mucus barrier and the GI symptoms related to cold and humid environmental stress; (2) the serum amino acid transferases such as glutamate pyruvic transa (GPT), and glutamic oxaloacetic transaminase (GOT) in cold and humid environmental stressed mice increased significantly, indicating that the intestinal microbiota adapted to cold and humid environmental stress by regulating the host's amino acid metabolism; (3) the integrative analysis of multi-omics illustrated a prediction model based on the microbiota Lactobacillus reuteri abundance and host amino acid level that can predict intestinal mucoprotein Muc2 with an adjusted R2 of 75.0%. In conclusion, the cold and humid environmental stress regulates the neurotransmitter amino acids metabolic function both in intestinal mucosal microbiota and host serum by adjusting the composition of the dominant bacterial population Lactobacillus reuteri, which contributes to the intestinal mucus barrier injury and GI disorders caused by cold and humid environmental stress.

Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells.

Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1. However, the roles of SIRT1 subcellular localization in PGCC formation and subsequent senescence escape remain unclear. In this study, we compared the differences in the polyploid cell population and senescence state of PGCCs following paclitaxel treatment between tumor cells overexpressing wild-type SIRT1 (WT SIRT1) and those expressing nuclear localization sequence (NLS)-mutated SIRT1 (SIRT1NLSmt ). We investigated the involvement of cytoplasmic SIRT1 in biological processes and signaling pathways, including the cell cycle and cellular senescence, in ovarian carcinoma cells' response to paclitaxel treatment. We found that the SIRT1NLSmt tumor cell population contained more polyploid cells and fewer senescent PGCCs than the SIRT1-overexpressing tumor cell population. Comparative proteomic analyses using co-immunoprecipitation (Co-IP) combined with liquid chromatography-mass spectrometry (LC-MS)/MS showed the differences in the differentially expressed proteins related to PGCC formation, cell growth, and death, including CDK1 and CDK2, between SIRT1NLSmt and SIRT1 cells or PGCCs. Our results suggested that ovarian carcinoma cells utilize polyploidy formation as a survival mechanism during exposure to paclitaxel-based treatment via the effect of cytoplasmic SIRT1 on PGCC formation and survival, thereby boosting paclitaxel resistance. © 2023 The Pathological Society of Great Britain and Ireland.

COL6A3 enhances the osteogenic differentiation potential of BMSCs by promoting mitophagy in the osteoporotic microenvironment.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) have been widely recognized as a highly promising option for cell-based tissue engineering therapy targeting osteoporosis. However, the osteogenic differentiation of BMSCs is impeded by the limited viability and diminished capacity for bone formation within the osteoporotic microenvironment. METHODS: In this study, the COL6A3 gene was confirmed through an extensive analysis of the preceding single-cell sequencing database. The generation of an inflammatory microenvironment resembling osteoporotic cell transplantation was achieved by employing lipopolysaccharide (LPS). A lentivirus targeting the COL6A3 gene was constructed, and a Western blotting assay was used to measure the marker proteins of osteogenesis, adipogenesis, and mitophagy. Immunofluorescence was utilized to observe the colocalization of mitochondria and lysosomes. The apoptosis rate of each group was evaluated using the TUNEL assay, and the mitochondrial membrane potential was assessed using JC-1 staining. RESULTS: This investigation discovered that the impaired differentiation capacity and decreased viability of BMSCs within the inflammatory microenvironment were markedly ameliorated upon overexpression of the specific COL6A3 gene. Moreover, the administration of COL6A3 gene overexpression successfully mitigated the inhibitory impacts of LPS on mitophagy and the expression of inflammatory mediators, specifically inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in BMSCs. To clarify the underlying mechanism, the role of mitophagy during the differentiation of COL6A3 gene-modified BMSCs in the inflammatory microenvironment was evaluated using the mitophagy inhibitor Mdivi-1. CONCLUSIONS: In the context of lipopolysaccharide (LPS) stimulation, COL6A3 enhances the differentiation of BMSCs into osteogenic and adipogenic lineages through the promotion of mitophagy and the maintenance of mitochondrial health. Our findings may provide a novel therapeutic approach utilizing stem cells in the treatment of osteoporosis.

On the numerical corroboration of an obstacle problem for linearly elastic flexural shells.

In this article, we study the numerical corroboration of a variational model governed by a fourth-order elliptic operator that describes the deformation of a linearly elastic flexural shell subjected not to cross a prescribed flat obstacle. The problem under consideration is modelled by means of a set of variational inequalities posed over a non-empty, closed and convex subset of a suitable Sobolev space and is known to admit a unique solution. Qualitative and quantitative numerical experiments corroborating the validity of the model and its asymptotic similarity with Koiter's model are also presented.This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Embryo injected with Ochratoxin A induced jejunum injury in ducklings by activating the TLR4 signaling pathway: Involvement of intestinal microbiota.

Ochratoxin A (OTA) is a common mycotoxin that causes intestinal injury in humans and various animal species. OTA may lead to intestinal injury in offspring due to the maternal effect. The aim of this study was to investigate the mechanism of embryo injected with OTA induced jejunum injury in ducklings. The results showed that OTA disrupted the jejunum tight junctions in hatching ducklings, and promoted the secretion of inflammatory cytokines. And this inflammatory response was caused by the activation of the TLR4 signaling pathway. Moreover, embryo injected with OTA could cause damage to the intestinal barrier in 21-day-old ducks, characterized by shortened villi, crypt hyperplasia, disrupted intestinal tight junctions, increased level of LPS in the jejunum, activation of the TLR4 signaling pathway, and increased levels of pro-inflammatory cytokines. Meanwhile, OTA induced oxidative stress in the jejunum. And dysbiosis of gut microbiota was mainly characterized by an increased the relative abundance of Bacteroides, Megamonas, Fournierella, and decreased the relative abundance of Alistipes and Weissella. Interestingly, embryo injected with OTA did not induce these changes in the jejunum of antibiotics-treated 21-day-old ducks. In conclusion, embryo injected with OTA induced jejunum injury in ducklings by activating the TLR4 signaling pathway, which involvement of intestinal microbiota.

Tissue damage, antioxidant capacity, transcriptional and metabolic regulation of red drum Sciaenops ocellatus in response to nanoplastics exposure and subsequent recovery.

Nanoplastics are recognized as emerging contaminants that can cause severe toxicity to marine fishes. However, limited researches were focusing on the toxic effects of nanoplastics on marine fish, especially the post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to 5 mg/L polystyrene nanoplastics (100 nm, PS-NPs) for a 7-day exposure experiment, and a 14-day recovery experiment that followed. The aim was to evaluate the dynamic alterations in hepatic and branchial tissue damage, hepatic antioxidant capacity, as well as hepatic transcriptional and metabolic regulation in the red drum during exposure and post-exposure to PS-NPs. Histopathological observation found that PS-NPs primarily triggered hepatic lipid droplets and branchial epithelial liftings, a phenomenon persistently discernible up to the 14 days of recovery. Although antioxidant capacity partially recovered during recovery periods, PS-NPs resulted in a sustained reduction in hepatic antioxidant activity, causing oxidative damage throughout the entire exposure and recovery phases, as evidenced by decreased total superoxide dismutase activities and increased malondialdehyde content. At the transcriptional and metabolic level, PS-NPs primarily induced lipid metabolism disorders, DNA damage, biofilm disruption, and mitochondrial dysfunction. In the gene-metabolite correlation interaction network, numerous CcO (cytochrome c oxidase) family genes and lipid metabolites were identified as key regulatory genes and metabolites in detoxification processes. Among them, the red drum possesses one additional CcO6B in comparison to human and zebrafish, which potentially contributes to its enhanced capacity for maintaining a stable and positive regulatory function in detoxification. This study revealed that nanoplastics cause severe biotoxicity to red drum, which may be detrimental to the survival of wild populations and affect the economics of farmed populations.

Effects and mechanisms of endocrine disruptor bisphenol AF on male reproductive health: A mini review.

Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.

Risk Factors of Intraoperative Pressure Injury in Adult Patients Undergoing Neurologic Surgery.

GENERAL PURPOSE: To present research investigating the incidence of and risk factors associated with intraoperative pressure injury in patients undergoing neurologic surgery at Xiangya Hospital, Central South University in China. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the incidence of intraoperative pressure injuries (PIs) in patients undergoing neurologic surgery at Xiangya Hospital, Central South University in China.2. Describe risk factors for intraoperative PI.3. Outline strategies to help mitigate intraoperative PI risk.

Intraoperative pressure injury (PI) development is an adverse event that impacts thousands of patients globally and is associated with extended hospital stays and increased risk of mortality. To investigate the incidence of intraoperative PI in patients undergoing neurologic surgery and identify associated risk factors. A total of 1,728 patients who underwent neurosurgery in Xiangya Hospital, Central South University between January 2021 and December 2022 were included in this retrospective study. The authors collected patients' demographic data and clinical characteristics and used univariate and multivariate regression to evaluate significant PI risk factors. Intraoperative PI was observed in 1.8% of all surgical cases (n = 31). Having a body mass index greater than 24 kg/m2 (odds ratio, 3.87; 95% CI, 1.62­9.23; P = .002), being in a lateral position (odds ratio, 2.53; 95% CI, 1.04­6.17; P = .042) or a prone position (odds ratio, 10.43; 95% CI, 3.37­32.23; P < .001), and having a longer operation time (cutoff point at 7.92 hours for increased risk of PI; odds ratio, 1.36; 95% CI, 1.21­1.53; P < .001) were significant risk factors for intraoperative PI. This study identified three independent risk factors for intraoperative PI development: body position, surgery duration, and high body mass index. These findings can help OR nurses identify patients who are vulnerable to intraoperative PI and provide appropriate preventive measures. For these patients, perioperative protection and frequent microrepositioning during surgery would be indispensable.

[Evaluation of augmented reality technology in the recognizing of oral and maxillofacial anatomy].

OBJECTIVE: To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy. METHODS: This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy. The image data were selected according to the experiment content, and the important blood vessels and bone tissue structures, such as upper and lower jaws, neck arteries and veins were reconstructed in 3D(3-dimensional) by digital software to generate experiment models, and the reconstructed models were encrypted and stored in the cloud. The QR (quick response) code corresponding to the 3D model was scanned by a networked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing. Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively. Subjects' feedback was collected in the form of a post-class questionnaire to evaluate the effectiveness of augmented reality technology-assisted recognizing. RESULTS: In the study, 83 undergraduate students were included as subjects in this study. Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy. All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud, and zoom in/out/rotate the model on the mobile. Augmented reality technology could provide personalized 3D model, based on learners' needs and abilities. The results of likert scale showed that augmented reality technology was highly recognized by the students (9.19 points), and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning (9.01 and 8.85 points respectively). CONCLUSION: Augmented reality technology can realize the three-dimensional visualization of important structures of oral and maxillofacial anatomy and stimulate students' enthusiasm for learning. Besides, it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area. The application of augmented reality technology achieves favorable effect in the recognizing of oral and maxillofacial anatomy.

[Clinical analysis of denture rehabilitation after mandibular fibula free-flap reconstruction].

OBJECTIVE: To evaluate the postoperative denture restoration and denture function in patients with mandibular defect reconstructed with vascularized free fibula flap. METHODS: In the study, 154 patients who underwent mandibular segment resection and used vascularized free fibula flap to repair mandibular defects due to inflammation, trauma and tumor from January 2015 to December 2020 were collected. These patients had common inclusion criteria which were stable occlusal relationship before operation, segmental defects of mandibular bone caused by lesions of mandible and adjacent parts (such as floor of mouth, tongue, cheek), free fibula flap used for repair and surviving after operation. Relevant data were reviewed and situation of denture restoration was followed up. A questionnaire related to denture functional evaluation had been proposed for those who had completed the denture rehabilitation. The evaluation index of denture restoration function was assigned by expert authority to obtain the denture function score. SPSS 18.0 software was used for statistical analysis of the basic information of the patients included in the study and the denture restoration of the patients. RESULTS: The rate of postoperative denture restoration in the patients with mandibular defects repaired by free fibula flap was 17.5%, and the rate of postoperative denture restoration in the patients with benign mandibular tumors was 25.0% (18/72), which was significantly greater than that in the patients with malignant tumors 11.0% (9/82, P < 0.05). There was no significant difference in denture function score between the patients with condylar defect and those without condylar defect in denture repair rate and denture function score (P>0.05). The functional score of implant denture was significantly greater than that of removable denture (P < 0.05). According to Brown classification, the denture function score of the patients with the defect invo-lving the anterior mandibular region was significantly greater than that of the patients without the anterior mandibular region involved (P < 0.05). The poor oral conditions, such as less amount of remaining teeth, insufficient retention strength, large mobility of soft tissue in the surgical area, poor oral vestibular groove condition became the main reason of not receiving denture restoration (37.86%). CONCLUSION: The denture rehabilitation of mandibular defect reconstructed with vascularized free fibula flap is closely rela-ted to pathological properties and oral conditions. The clinical outcome of implant denture has been confirmed effectively and it is a better choice for future denture restoration after mandibular reconstruction.