Spatial and diel variations of bacterioplankton and pico-nanoeukaryote communities and potential biotic interactions during macroalgal blooms.

We investigated spatial heterogeneity and diel variations in bacterioplankton and pico-nanoeukaryote communities, and potential biotic interactions at the extinction stage of the Ulva prolifera bloom in the Jiaozhou Bay, Yellow Sea. It was found that the presence of Ulva canopies significantly promoted the cell abundance of heterotrophic bacteria, raised evenness, and altered the community structure of bacterioplankton. A diel pattern was solely significant for pico-nanoeukaryote community structure. >50 % of variation in the heterotrophic bacterial abundance was accounted for by the ratio of Bacteroidota to Firmicutes, and dissolved organic nitrogen effectively explained the variations in cell abundances of phytoplankton populations. The factors representing biotic interactions frequently contributed substantially more than environmental factors in explaining the variations in diversity and community structure of both bacterioplankton and pico-nanoeukaryotes. There were higher proportions of eukaryotic pathogens compared to other marine systems, suggesting a higher ecological risk associated with the Ulva blooms.

High glucose-induced p66Shc mitochondrial translocation regulates autophagy initiation and autophagosome formation in syncytiotrophoblast and extravillous trophoblast.

BACKGROUND: p66Shc, as a redox enzyme, regulates reactive oxygen species (ROS) production in mitochondria and autophagy. However, the mechanisms by which p66Shc affects autophagosome formation are not fully understood. METHODS: p66Shc expression and its location in the trophoblast cells were detected in vivo and in vitro. Small hairpin RNAs or CRISPR/Cas9, RNA sequencing, and confocal laser scanning microscope were used to clarify p66Shc's role in regulating autophagic flux and STING activation. In addition, p66Shc affects mitochondrial-associated endoplasmic reticulum membranes (MAMs) formation were observed by transmission electron microscopy (TEM). Mitochondrial function was evaluated by detected cytoplastic mitochondrial DNA (mtDNA) and mitochondrial membrane potential (MMP). RESULTS: High glucose induces the expression and mitochondrial translocation of p66Shc, which promotes MAMs formation and stimulates PINK1-PRKN-mediated mitophagy. Moreover, mitochondrial localized p66Shc reduces MMP and triggers cytosolic mtDNA release, thus activates cGAS/STING signaling and ultimately leads to enhanced autophagy and cellular senescence. Specially, we found p66Shc is required for the interaction between STING and LC3II, as well as between STING and ATG5, thereby regulates cGAS/STING-mediated autophagy. We also identified hundreds of genes associated several biological processes including aging are co-regulated by p66Shc and ATG5, deletion either of which results in diminished cellular senescence. CONCLUSION: p66Shc is not only implicated in the initiation of autophagy by promoting MAMs formation, but also helps stabilizing active autophagic flux by activating cGAS/STING pathway in trophoblast.

Synthesis of Pyrimido[1,2-a]indolediones and Pyrimidinediones via [4+2] Annulation of 2H-Azirine-2-carbaldehydes.

NHC-catalyzed [4+2] annulation of 2H-azirine-2-carbaldehydes with ketimines and isocyanates has been developed, providing straightforward synthetic protocols for constructing structurally intriguing pyrimido[1,2-a]indolediones and pyrimidinediones under mild conditions with excellent yields. This protocol can be used to synthesize the core skeleton of pharmaceutically important drugs and pyrimido[1,2-a]indoledione-containing natural products, making it potentially valuable for creating biologically active derivatives.

Selenium Nanomaterials Enhance the Nutrients and Functional Components of Fuding Dabai Tea.

Theanine, polyphenols, and caffeine not only affect the flavor of tea, but also play an important role in human health benefits. However, the specific regulatory mechanism of Se NMs on fat-reducing components is still unclear. In this study, the synthesis of fat-reducing components in Fuding Dabai (FDDB) tea was investigated. The results indicated that the 100-bud weight, theanine, EGCG, total catechin, and caffeine contents of tea buds were optimally promoted by 10 mg·L-1 Se NMs in the range of 24.3%, 36.2%, 53.9%, 67.1%, and 30.9%, respectively. Mechanically, Se NMs promoted photosynthesis in tea plants, increased the soluble sugar content in tea leaves (30.3%), and provided energy for the metabolic processes, including the TCA cycle, pyruvate metabolism, amino acid metabolism, and the glutamine/glutamic acid cycle, ultimately increasing the content of amino acids and antioxidant substances (catechins) in tea buds; the relative expressions of key genes for catechin synthesis, CsPAL, CsC4H, CsCHI, CsDFR, CsANS, CsANR, CsLAR, and UGGT, were significantly upregulated by 45.1-619.1%. The expressions of theanine synthesis genes CsTs, CsGs, and CsGOGAT were upregulated by 138.8-693.7%. Moreover, Se NMs promoted more sucrose transfer to the roots, with the upregulations of CsSUT1, CsSUT2, CsSUT3, and CsSWEET1a by 125.8-560.5%. Correspondingly, Se NMs enriched the beneficial rhizosphere microbiota (Roseiarcus, Acidothermus, Acidibacter, Conexicter, and Pedosphaeraceae), enhancing the absorption and utilization of ammonium nitrogen by tea plants, contributing to the accumulation of theanine. This study provides compelling evidence supporting the application of Se NMs in promoting the lipid-reducing components of tea by enhancing its nitrogen metabolism.

Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

BACKGROUND: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. METHODS: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. RESULTS: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). CONCLUSIONS: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

A rational designed multi-epitope vaccine elicited robust protective efficacy against Klebsiella pneumoniae lung infection.

BACKGROUND: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. METHODS AND RESULTS: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. CONCLUSIONS: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.

Nutritional strategies to reduce intestinal cell apoptosis by alleviating oxidative stress.

The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.

pH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Analysis of predictive factors in surgical treatment of intractable epilepsy caused by focal cortical dysplasia in children.

OBJECTIVE: This study aims to analyze key factors affecting the surgical outcome of children with intractable epilepsy caused by focal cortical dysplasia, providing more effective clinical guidance. METHODS: We conducted a study from March 2019 to February 2021, selecting 80 children with intractable epilepsy caused by focal cortical dysplasia who underwent surgical treatment. Comprehensive inclusion criteria were met. We collected general information and treatment outcomes before and after surgery, with a two-year postoperative follow-up. Patients were categorized into good and poor outcome groups based on outcomes. Various factors including pathological types, age of onset, seizure frequency, and extent of resection were selected as variables. Logistic regression analysis investigated predictive factors. RESULTS: Engel class I included 53 cases, class II had 16 cases, class III had 9 cases, and class IV had 2 cases. Thus, 53 cases were in the good outcome group, and 27 in the poor outcome group. General data showed no significant differences between the groups (p > 0.05). Single-factor analysis revealed statistically significant risk factors: FCD classification, MRI results, age of onset, seizure frequency, and extent of resection (p < 0.05). Logistic multifactor analysis indicated seizure frequency. acute postoperative seizures (APSO) and extent of resection as independent influencing factors (p < 0.05). CONCLUSION: Seizure frequency, extent of resection, and APSO are key independent factors for surgical outcome in children with intractable epilepsy caused by focal cortical dysplasia. Clinicians should consider these factors when planning treatment to improve success rates and outcome, enhancing quality of life for affected children.

Exploration of the Amino Acid Metabolic Profiling and Pathway in Clonorchis sinensis-Infected Rats Revealed by the Targeted Metabolomic Analysis.

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and ß-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1ß. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; ß-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level.

Nano-Structure Evolution and Mechanical Properties of AlxCoCrFeNi2.1 (x = 0, 0.3, 0.7, 1.0, 1.3) High-Entropy Alloy Prepared by Mechanical Alloying and Spark Plasma Sintering.

The AlxCoCrFeNi2.1 (x = 0, 0.3, 0.7, 1.0, 1.3) multi-component high-entropy alloy (HEA) was synthesized by mechanical alloying (MA) and Spark Plasma Sintering (SPS), The impact of the percentage of Al on crystal structure transition, microstructure evolution and mechanical properties were studied. Crystal structure was investigated by X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The results show that with the increasing of Al content, the crystal structure of the alloys gradually transformed from a nanocrystalline phase of FCC to a mix of FCC and BCC nanocrystalline. The hardness was found to increase steadily from 433 HV to 565 HV due to the increase in fraction of BCC nanocrystalline phase. Thus, the compressive fracture strength increased from 1702 MPa to 2333 MPa; in contrast, the fracture strain decreased from 39.8% to 15.6%.

Both partial inactivation as well as activation of NF-κB signaling lead to hypertension and chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Activation of NF-κB-signalling is key in the pathogenesis of chronic kidney diseases (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair. METHODS: To investigate the relationship between activated and inactivated NF-κB signaling on the pathogenesis of CKD using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine). RESULTS: The density of CD3, CD8, CD68 positive cells, as well as the expression of IL-6, TRAF-1, and NAF-1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by PAS-, Masson trichrome-, and Sirius-Red-staining as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine-ratio are markedly increased in NF-κB activated and inactivated mice compared to controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared to wild-type mice. CONCLUSIONS: Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.

Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults.

BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

Flower development and a functional analysis of related genes in Impatiens uliginosa.

Impatiens uliginosa is a plant of the Impatiens, with peculiar flowers. In this study, we combined morphogenesis and molecular biology to explore its development of flowers. An analysis of basic observational data and paraffin sectioning showed that it took approximately 13 d for the floral organs to differentiate. An analysis of the development of inflorescences and floral organs by scanning electron microscopy showed that the inflorescence of I. uliginosa is a spiral raceme. The floral organs differentiated in the following order: lateral sepals (Ls), posterior sepal (Ps), anterior sepals (As), anterior petal (Ap), lateral petals (Lp), stamens (St) and gynoecium (Gy). I. uliginosa was found to have four sepals, and the connate stamens are caused by the fusion and growth of filament appendages. The results of fluorescence quantification and virus-induced gene silencing showed that I. uliginosa had its own unique model for flower development, and there was functional diversity of IuAP1 and IuDEF. Among them, IuAP1 controls the formation of bract s (Br), regulates the morphogenesis of posterior sepal, controls the anthocyanin precipitation of the anterior petals and the formation of lateral petals. IuDEF regulates the morphogenesis of lateral sepals, the length of development of the spur, and controls the size of yellow flower color plaques of the lateral petals. In this study, the process of flower development and the function of flower development genes of I. uliginosa were preliminarily verified. This study provides basic guidance and new concepts that can be used to study the development of Impatiens flowers.

The Value of Computer Vision in Identifying the Bone of Dialysis Patients.

BACKGROUND: In the end stage of kidney disease, abnormal levels of blood calcium, phosphorus, and parathyroid hormone lead to bone metabolism disorders, manifesting as osteoporosis or fibrocystic osteoarthritis. X-ray, CT, and MR are useful for detecting bone lesions in dialysis patients, but currently, computer vision has not yet been used for this purpose. METHODS: ResNet is a powerful deep CNN model, which has not yet been used to distinguish between the bones of dialysis patients and healthy people. Therefore, this study aimed to investigate the ability of the Resnet50 model to identify the bone of dialysis patients from normal bone. RESULTS: CT images of 200 cases (100 dialysis patients and 100 healthy people aged 31-72 years with male:female ratio of 51:49) were randomly divided into the training and testing groups at the ratio of 8:2. The module of 'torch' was used to train the model of Resnet50 for the current task of image classification. In the test cohort, the accuracy, sensitivity, and specificity with hyper-parameter=0 were 60%, 65%, and 55%, respectively. When the hyper-parameter was 0.6 or 0.7 versus 0, the accuracy was significantly higher (P<0.05). When the hyper-parameter was another number, the accuracy was not significantly different from that with no hyper-parameter (P>0.05). CONCLUSION: This study has indicated computer vision to be suitable for identifying bone changes caused by dialysis; a hyper-parameter has been found necessary for improving model accuracy. The ResNet50 model with hyper-parameter = 0.7 has exhibited 90% sensitivity in identifying the bone of dialysis patients.

Post-infusion PD-1+CD8+CAR-T cells identify patients responsive to CD19-CAR-T therapy in non-Hodgkin's lymphoma.

Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized treatment for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). Robust biomarkers and a complete understanding of CAR-T cell function in the post-infusion phase remain limited. Here we used a 37-color spectral flow cytometry panel to perform high dimensional single cell analysis of post-infusion samples in 26 patients treated with CD28 co-stimulatory domain containing commercial CAR-T (CD28-CAR-T) for NHL and focused on computationally gated CD8+ CAR-T cells. We found that the presence of post-infusion PD-1+ CD8+ CAR-T cells at the Day 14 timepoint highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR-T cells including PD-1+ TCF1+ stem-like CAR-T cells and PD-1+ TIM3+ effector-like CAR-T cells that correlated with improved clinical outcomes such as response and progression free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with Grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here we identified robust biomarkers of response to CD28-CAR-T and highlight the importance of PD-1 positivity in CD8+ CAR-T cells post-infusion in achieving CR.

Rehabilitation with brain-computer interface and upper limb motor function in ischemic stroke: A randomized controlled trial.

BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).

Dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces oxidative damage promoting cell apoptosis primarily via mitochondrial pathway in the hepatopancreas of carp, Cyprinus carpio.

To investigate the mechanisms of BDE-47 on hepatotoxicity in fish, this study examined the effects of dietary exposure to BDE-47 (40 and 4000 ng/g) on carp for 42 days. The results showed that BDE-47 significantly increased carp's condition factor and hepatosomatic index. Pathological results revealed unclear hepatic cord structure, hepatocytes swelling, cellular vacuolization, and inflammatory cell infiltration in the hepatopancreas of carp. Further investigation showed that ROS levels significantly increased on days 7, 14, and 42. Moreover, the activities of antioxidant enzymes SOD, GSH, CAT, and GST increased significantly from 1 to 7 days, and the transcription levels of antioxidant enzymes CAT, Cu-Zn SOD, Mn-SOD, GST, and GPX, and antioxidant pathway genes Keap1, Nrf2, and HO-1 changed significantly at multiple time-points during the 42 days. The results of apoptosis pathway genes showed that the mitochondrial pathway genes Bax, Casp3, and Casp9 were significantly upregulated and Bcl2 was significantly downregulated, while the transcription levels of FADD and PERK were significantly enhanced. These results indicate that BDE-47 induced oxidative damage in hepatopancreas, then it promoted cell apoptosis mainly through the mitochondrial pathway. This study provides a foundation for analyzing the mechanism of hepatotoxicity induced by BDE-47 on fish.

Minimally invasive surgical removal of bilateral impacted mandibular supernumerary teeth using 3D surgical guide template: a case report.

Impacted supernumerary teeth are defined as the presence of one or more teeth in a patient's upper and lower jaws in addition to the normal number of teeth in the dental arch. It has an incidence rate of approximately 1%-14% and more frequently occurs in males than females, may be single or multiple, unilateral or bilateral, erupted or impacted. In this article, we describe the case of a patient with two supernumerary teeth between the roots of the mandibular second premolar and the first molar, which influenced the effectiveness of the first orthodontic treatment. The special anatomical position of the complex supernumerary teeth made tooth extraction challenging. Given the higher risk status of surgery, we implemented a novel tooth extracting technique for this patient. Thus, in this study, we describe a case of minimally invasive extraction of bilateral mandibular impacted supernumerary teeth using a digital 3D positioning guide plate.

One-step creation of CMS lines using a BoCENH3-based haploid induction system in Brassica crop.

Heterosis utilization in a large proportion of crops depends on the use of cytoplasmic male sterility (CMS) tools, requiring the development of homozygous fertile lines and CMS lines1. Although doubled haploid (DH) technology has been developed for several crops to rapidly generate fertile lines2,3, CMS lines are generally created by multiple rounds of backcrossing, which is time consuming and expensive4. Here we describe a method for generating both homozygous fertile and CMS lines through in vivo paternal haploid induction (HI). We generated in-frame deletion and restored frameshift mutants of BoCENH3 in Brassica oleracea using the CRISPR/Cas9 system. The mutants induced paternal haploids by outcrossing. We subsequently generated HI lines with CMS cytoplasm, which enabled the generation of homozygous CMS lines in one step. The BoCENH3-based HI system provides a new DH technology to accelerate breeding in Brassica and other crops.