[Chemical components and in vitro anti-aging activity of Yangxue Qingnao Wan based on UPLC-Q-TOF-MS/MS].

The main chemical components of Yangxue Qingnao Wan(YXQNW) were analyzed and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). According to the mass spectrometry information, Mass Hunter 10.0 analysis software was used to compare the collected quasi-molecular ion peaks and secondary fragment ions with literature and reference substances. A total of 131 compounds were identified from YXQNW, including 11 phenylpropanoids, 11 flavonoids, 42 nitrogen-containing compounds, 12 terpenoids, 17 phthalides, 23 quinones, and 15 other compounds. The anti-aging activity of YXQNW and six compounds from YXQNW, including rosmarinic acid, gallic acid, rutin, umbelliferone, hyperoside, and vanillic acid, were evaluated by D-galactose(D-gal)-induced HT22 cell senescence model. The effects of the compounds on HT22 cell damage and individual cell proliferation ability were observed from overall and individual perspectives by the Beyo Click~(TM) EdU-555 cell proliferation kit, and apoptosis was detected by the Annexin V-FITC/PI double staining apoptosis detection kit. Finally, the anti-aging effect of the compounds was tested by a cell senescence ß-galactosidase staining kit. This study provides a more comprehensive analysis of the chemical components of YXQNW and evaluates its anti-aging effect, which will provide a scientific basis for basic research on the efficacy of YXQNW for the treatment of various neurological diseases, such as Alzheimer's disease(AD), headache, and memory loss.

Defect Engineering of Ultrasmall TiO2 Nanoparticles Enables Highly Efficient Photocatalysts for Solar H2 Production from Woody Biomass.

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation.

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Effects of Leydig cell elimination on testicular interstitial cell populations: characterization by scRNA-seq and immunocytochemical techniques.

Background: The mammalian testicular interstitial cells are not well-defined. The present study characterized the interstitial cell types and their turnover dynamics in adult rats. Additionally, the heterogeneity of the mesenchymal population and the effects of Leydig cell elimination on interstitial homeostasis were further analyzed by scRNA-seq datasets and immunocytochemical techniques. Methods: Interstitial cells were defined at the transcriptomic level by scRNA-seq and then confirmed and quantified with protein markers. The dividing activity of the major cell types was determined by continuous EdU labeling of the animals for one week. Some of the rats were also treated with a dose of ethylenedimethylsulfonate (EDS) to examine how the loss of Leydig cells (LCs) could affect interstitial homeostasis for three weeks. Results: Seven interstitial cell types were identified, including cell types (percentage of the whole interstitial population) as follows: Leydig (44.6%), macrophage and dendritic (19.1%), lymphoid (6.2%), vascular endothelial (7.9%), smooth muscle (10.7%), and mesenchymal (11.5%) cells. The EdU experiment indicated that most cell types were dividing at relatively low levels (<9%) except for the mesenchymal cells (MCs, 17.1%). Further analysis of the transcriptome of MCs revealed 4 subgroups with distinct functions, including 1) glutathione metabolism and xenobiotic detoxification, 2) ROS response and AP-1 signaling, 3) extracellular matrix synthesis and binding, and 4) immune response and regulation. Stem LCs (SLCs) are primarily associated with subgroup 3, expressing ARG1 and GAP43. EDS treatment not only eliminated LCs but also increased subgroup 3 and decreased subgroups 1 and 2 of the mesenchymal population. Moreover, EDS treatment increased the division of immune cells by more than tenfold in one week. Conclusion: Seven interstitial cell types were identified and quantified for rat testis. Many may play more diversified roles than previously realized. The elimination of LCs led to significant changes in MCs and immune cells, indicating the importance of LCs in maintaining testicular interstitial homeostasis.

DCC in the cerebral cortex is required for cognitive functions in mouse.

Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3α/ß were decreased, which was responsible for impaired PPI in the DCC-deficient mice. Finally, the DCC-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.

Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy.

BACKGROUND: Combining interleukin-2 (IL-2) with radiotherapy (RT) and immune checkpoint blockade (ICB) has emerged as a promising approach to address ICB resistance. However, conventional IL-2 cytokine therapy faces constraints owing to its brief half-life and adverse effects. RDB 1462, the mouse ortholog of Nemvaleukin alfa, is an engineered IL-2 with an intermediate affinity that selectively stimulates antitumor CD8 T and NK cells while limiting regulatory T cell expansion. This study aimed to evaluate the antitumor activity and mechanism of action of the combination of RDB 1462, RT, and anti-PD1 in mouse tumor models. METHODS: Two bilateral lung adenocarcinoma murine models were established using 344SQ-Parental and 344SQ anti-PD1-resistant cell lines. Primary tumors were treated with RT, and secondary tumors were observed for evidence of abscopal effects. We performed immune phenotyping by flow cytometry, analyzed 770 immune-related genes using NanoString, and performed T cell receptor (TCR) repertoire analysis. Serum pro-inflammatory cytokine markers were analyzed by 23-plex kit. RESULTS: Compared to native IL-2 (RDB 1475), RDB 1462 demonstrated superior systemic antitumoral responses, attributable, at least in part, to augmented levels of CD4 and CD8 T cells with the latter. Our findings reveal substantial reductions in primary and secondary tumor volumes compared to monotherapy controls, with some variability observed among different dosing schedules of RDB 1462 combined with RT. Blood and tumor tissue-based flow cytometric phenotyping reveals an increase in effector memory CD8 and CD4 T cells and a decrease in immunosuppressive cells accompanied by a significant increase in IL-2, IFN-γ, and GM-CSF levels in the combination group. Transcriptomic profiling and TCR sequencing reveal favorable gene expression and T cell repertoire patterns with the dual combination. Furthermore, integrating anti-PD1 therapy with RT and RDB 1462 further reduced primary and secondary tumor volumes, prolonged survival, and decreased lung metastasis. Observations of immune cell profiles indicated that RT with escalating doses of RDB 1462 significantly reduced tumor growth and increased tumor-specific immune cell populations. CONCLUSION: The addition of Nemvaleukin therapy may enhance responses to RT alone and in combination with anti-PD1.

Development and psychometric testing of the nurses' core competencies for public health emergencies scale: A multicenter cross-sectional study.

BACKGROUND: The significance of addressing public health emergencies (PHEs) emphasizes the pivotal role of a skilled nursing workforce in effective preparedness and response. However, there's a lack of comprehensive assessments tailored to nurses' core competencies, serving as a standard for ongoing education in preparedness. OBJECTIVE: This study aimed to develop a psychometrically sound scale for identifying and measuring essential core competencies crucial for nurses during public health emergencies. DESIGN: A multicenter cross-sectional study was conducted. SETTINGS: Twelve tertiary hospitals in Shanghai. PARTICIPANTS: Affiliated nurses with prior experience and significant exposure to public health emergencies were recruited. METHODS: The study underwent development and validation in two stages, utilizing qualitative data analysis, a Delphi expert panel, and an empirical quantitative cross-sectional survey. The Nurses' Core Competencies for Public Health Emergencies (NCC-PHEs) scale and a demographic questionnaire were distributed between January 2023 and March 2023. Exploratory factor analysis, confirmatory factor analysis, Pearson correlations, and Cronbach's alpha analyses were employed to identify theoretical constructs, assess scale reliability, and establish validity. RESULTS: Analysis was conducted on valid data collected from 1481 nurses. Factor analysis identified 47 professional nursing competencies arranged within a four-factor high-order model: prevention competencies (9 items), preparation competencies (7 items), response competencies (comprising basic and advanced levels) (26 items), and recovery competencies (5 items). Structural equation modelling confirmed satisfactory factor loadings and a good model fit, validating construct integrity. The reliability of the total scale was confirmed. CONCLUSION: This study presents a valid scale that empirically measures nurses' core competencies crucial for preparedness and response during public health emergencies. The findings offer instrumental support for guiding the development of future courses and training programs in nursing research and practice.

Britannilactone 1-O-acetate induced ubiquitination of NLRP3 inflammasome through TRIM31 as a protective mechanism against reflux esophagitis-induced esophageal injury.

BACKGROUND: Reflux esophagitis (RE) is a disease in which inflammation of the esophageal mucosa owing to the reflux of gastric contents into the esophagus results in cytokine damage. Britannilactone 1-O-acetate (Brt) has anti-inflammatory effects, significantly inhibiting the activation of the NLRP3 inflammasome, leading to a decrease in inflammatory factors including IL-1 ß, IL-6, and TNF-α. However, the mechanism underlying its protective effect against RE-induced esophageal injury remains unclear. In the present study, we investigated the protective mechanism of TRIM31 against NLRP3 ubiquitination-induced RE both in vivo and in vitro. METHODS: A model of RE was established in vivo in rats by the method of "4.2 mm pyloric clamp + 2/3 fundoplication". In vitro, the mod was constructed by using HET-1A (esophageal epithelial cells) and exposing the cells to acid, bile salts, and acidic bile salts. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to screen the concentration of administered drugs, and the viability of HET-1A cells in each group. HE staining was used to assess the degree of pathological damage in esophageal tissues. Toluidine blue staining was used to detect whether the protective function of the esophageal epithelial barrier was damaged and restored. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-1 ß, IL-6, and TNF-α factors in serum. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3 in esophageal tissues. The molecular docking and Co-immunoprecipitation assay (Co-IP assay) were used to detect the TRIM31 interacts with NLRP3. Western blotting detected the Claudin-4, Claudin-5, The G-protein-coupled receptor calcium-sensitive receptor (CaSR), NLRP3, TRIM31, ASC, C-Caspase1, and Caspase1 protein expression levels. RESULTS: Brt could alleviate RE inflammatory responses by modulating serum levels of IL-1 ß, IL-6, and TNF-α. It also activated the expression of NLRP3, ASC, Caspase 1, and C-Caspase-1 in HET-1A cells. Brt also attenuated TRIM31/NLRP3-induced pathological injury in rats with RE through a molecular mechanism consistent with the in vitro results. CONCLUSIONS: Brt promotes the ubiquitination of NLRP3 through TRIM31 and attenuates esophageal epithelial damage induced by RE caused by acidic bile salt exposure. This study provides valuable insights into the mechanism of action of Brt in the treatment of RE and highlights its promising application in the prevention of NLRP3 inflammatory vesicle-associated inflammatory pathological injury.

Dietary Zn proteinate with moderate chelation strength alleviates heat stress-induced intestinal barrier function damage by promoting expression of tight junction proteins via the A20/NF-κB p65/MMP-2 pathway in the jejunum of broilers.

BACKGROUND: The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included. RESULTS: The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1ß contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1ß contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20. CONCLUSIONS: Our results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes.

BACKGROUND: Insulin antibodies (IAs) affect blood glucose control in patients receiving insulin therapy. AIM: To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional, retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy. All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array. RESULTS: A total of 1863 patients were enrolled. There were 902 (48.4%) patients who had positive IAs (IA level > 5%), with a mean IA level of 11.06% (10.39%-11.72%). IA levels were positively correlated with high fasting blood glucose (odds ratio = 1.069, P < 0.001). The proportion of positive IAs was lowest in patients using glargine only (31.9%) and highest in patients using human insulin only (70.3%), P < 0.001. The IA levels in patients using sulfonylureas/glinides (8.3%), metformin (9.6%), and dipeptidyl peptidase-4 inhibitors (8.2%) were all lower than in patients without these drugs (all P < 0.05). CONCLUSION: Nearly half of patients on insulin therapy have positive IA antibodies, and IA antibody levels are associated with blood glucose control. Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Changes in Craniofacial Morphology Induced by Unilateral Nasal Obstruction in Mice of Different Ages.

BACKGROUND: Nasal obstruction in humans leads to mouth breathing and subsequent hypoxia in the entire body. Furthermore, nasal obstruction in growing children affects craniofacial growth and development. OBJECTIVE: To investigate the effects of unilateral nasal obstruction (UNO) on craniofacial growth in mice of different ages, particularly on the morphology of the nasomaxillary complex and mandible. METHODS: Mice aged 3, 6 and 12 weeks were selected as representatives of juvenile, adolescent and adult stages, respectively. A total of 30 male C57BL/6J mice (10 mice each at the ages of 3, 6 and 12 weeks) were used in this study for a 3-week experiment. The mice in each age stage were randomly and evenly assigned to either the control group (C3+3, C6+3 and C12+3) or the experimental group (E3+3, E6+3 and E12+3). The UNO model in experimental group was constructed by plugging the mouse's left nostril, thereby disrupting its normal nasal breathing pattern and inducing hypoxia. The control group underwent the sham procedure. After 3 weeks, the length, width and height of the cranium, nasomaxillary complex and mandible of each group were measured on two-dimensional images constructed by micro-computed tomography. Furthermore, the impact of UNO on mouse growth was evaluated through the measurement of femoral length. RESULTS: In juvenile mice, UNO inhibited the growth of cranial width, cranial height and mandibular length. In adolescent mice, UNO impeded the growth of the femoral length, cranial length, nasomaxillary length and mandibular length. In adult mice, no significant negative effects of UNO on craniofacial growth were found. CONCLUSION: Referring to the experimental results, in addition to actively treating nasal obstruction in patients, it is important to monitor the growth of the mandible in juveniles, as well as the nasomaxillary and mandibular growth in adolescents during orthodontic clinical practice.

Effects of roxadustat on thyroid hormone levels and blood lipid metabolism in patients undergoing hemodialysis: a retrospective study.

Background: Roxadustat is commonly used to treat renal anemia. However, the potential effects of roxadustat on metabolism and organs other than the kidneys have recently attracted increased attention. Objective: This study aimed to examine the regulatory effects of roxadustat on thyroid hormones and blood lipid metabolism in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. Methods: Eighty ESKD patients on hemodialysis and taking roxadustat were enrolled. Hemoglobin, thyroid hormones (TSH, FT3, FT4), and blood lipid profiles (TC, LDL-C, TG, HDL-C) were assessed before and after treatment. Changes in these parameters were compared, and relevant causative factors were analyzed. Results: Roxadustat significantly increased Hb, lowered TSH, FT4, TC, and LDL-C levels (all P<0.001). Patients were categorized into three groups based on post-treatment TSH inhibition percentage: Q1(≥70%), Q2(30%-70%), Q3(≤30%). Pre-treatment TSH decreased with reduced TSH inhibition (P<0.05). Post-treatment, TC, LDL-C, TSH, FT3, and FT4 increased with reduced TSH inhibition (all P<0.05).TC and LDL-C significantly decreased post-treatment in Q1 and Q2 (P<0.05). Correlation analysis showed a positive correlation between ΔTSH and pre-treatment TSH levels (r=0.732, P<0.001). The proportion of patients with ≥70% TSH inhibition increased with higher pre-treatment TSH levels (P for trend <0.05). ΔLDL-C and ΔTSH were positively correlated (r=0.278, P<0.05), with ΔTSH identified as an influencing factor in multiple linear regression (ß=0.133, 95% CI [0.042, 0.223], P<0.05). Conclusion: Roxadustat effectively improves anemia in ESKD patients while inhibiting TSH and FT4 secretion and reducing TC and LDL-C levels. Decreases in TSH levels correlate with baseline TSH levels, and lowered blood lipid levels are associated with decreased TSH levels.

Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study.

Objective: In this prospective observational study, we aimed to investigate the serum levels of sirtuin (SIRT)3 in epilepsy patients and its association with the severity of the disease. Methods: This prospective observational study included 203 patients with symptomatic epilepsy and 100 healthy controls who visited our hospital from November 2019 to November 2022. The severity of the disease in epilepsy patients was assessed using the National Hospital Seizure Severity Scale (NHS3). We used enzyme-linked immunosorbent assay to measure the serum levels of SIRT3, interleukin (IL)-6, IL-1ß, tumor necrosis factor-alpha, and C-reactive protein in all patients. In addition, the cognitive function of all study participants was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment (MOCA). All data were analyzed using SPSS 25.0 software. Results: The MOCA scores of the epilepsy patients were significantly lower compared to the healthy volunteers (P < 0.05). The serum SIRT3 levels were decreased significantly in patients with refractory epilepsy (183.16 ± 17.22 pg/mL) compared to non-refractory epilepsy patients (199.00 ± 18.68 pg/mL). In addition, serum SIRT3 levels were negatively correlated with the inflammatory factors IL-6 (Pearson's correlation -0.221, P = 0.002) and NHS score (Pearson's correlation -0.272, P < 0.001) of epilepsy patients, while positively correlated with MOCA scores (Pearson's correlation 0.166, P = 0.018). Furthermore, the receiver operating characteristic curve demonstrated that serum SIRT3 could be used to diagnose epilepsy, as well as refractory epilepsy. Finally, logistic regression analysis showed that SIRT3 (OR = 1.028, 95%CI: 1.003-1.054, P = 0.028), IL-6 (OR = 0.666, 95%CI: 0.554-0.800, P < 0.001), IL-1ß (OR = 0.750, 95%CI: 0.630-0.894, P = 0.001), and NHS3 (OR = 0.555, 95%CI: 0.435-0.706, P < 0.001) were risk factors for refractory epilepsy. Conclusion: In conclusion, our findings demonstrated that serum SIRT3 levels were significantly decreased in epilepsy patients and further decreased in patients with refractory epilepsy. This study might provide new therapeutic targets and comprehensive treatment strategies for epilepsy patients.

Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum.

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

N/O co-doped poly(γ-glutamic acid)/Ni2+/melamine/chitosan nanoparticle-based hollow graphite carbon spheres for aqueous zinc-ion hybrid supercapacitors.

Hollow carbon spheres (HCSs) have attracted broad attention in aqueous zinc-ion hybrid supercapacitors (ZIHSCs) owing to their distinctive properties. However, traditional methods for fabricating HCSs face limitations, including complex multistep procedures, the use of corrosive chemicals, and stringent reaction conditions. In this work, biomass-based poly(γ-glutamic acid)/Ni2+/melamine/chitosan nanoparticles were used as the precursors to fabricate N/O co-doped hollow graphite carbon spheres (HGCSs). Thanks to the appropriate hydrophilic characteristic, specific surface area, pore size distribution, and electrical conductivity, the fabricated HGCSs cathode exhibited superior electrochemical properties. The assembled HGCSs-based ZIHSCs device showed a satisfactory specific capacitance of 133.2 mAh·g-1 at a current density of 1.0 A·g-1, high energy densities of 75.2 Wh·kg-1 at 10,000 W·kg-1 and 107.9 Wh·kg-1 at 1000 W·kg-1, respectively. Additionally, the assembled HGCSs-based ZIHSCs device displayed an exceptional cycling stability, enduring up to 10,000 cycles at 0.5 A·g-1 with a capacity retention rate of 98.1 %. This work provides a facile and novel strategy to prepare superior electrochemical performance biomass-based HGCSs cathode for ZIHSCs.

DC-YOLOv5-based target detection algorithm for cervical vertebral maturation.

The cervical vertebral maturation (CVM) method is essential to determine the timing of orthodontic and orthopedic treatment. In this paper, a target detection model called DC-YOLOv5 is proposed to achieve fully automated detection and staging of CVM. A total of 1800 cephalometric radiographs were labeled and categorized based on the CVM stages. We introduced a model named DC-YOLOv5, optimized for the specific characteristics of CVM based on YOLOv5. This optimization includes replacing the original bounding box regression loss calculation method with Wise-IOU to address the issue of mutual interference between vertical and horizontal losses in Complete-IOU (CIOU), which made model convergence challenging. We incorporated the Res-dcn-head module structure to enhance the focus on small target features, improving the model's sensitivity to subtle sample differences. Additionally, we introduced the Convolutional Block Attention Module (CBAM) dual-channel attention mechanism to enhance focus and understanding of critical features, thereby enhancing the accuracy and efficiency of target detection. Loss functions, precision, recall, mean average precision (mAP), and F1 scores were used as the main algorithm evaluation metrics to assess the performance of these models. Furthermore, we attempted to analyze regions important for model predictions using gradient Class Activation Mapping (CAM) techniques. The final F1 scores of the DC-YOLOv5 model for CVM identification were 0.993, 0.994 for mAp0.5 and 0.943 for mAp0.5:0.95, with faster convergence, more accurate and more robust detection than the other four models. The DC-YOLOv5 algorithm shows high accuracy and robustness in CVM identification, which provides strong support for fast and accurate CVM identification and has a positive effect on the development of medical field and clinical diagnosis.

Dietary manganese supplementation decreases hepatic lipid deposition by regulating gene expression and enzyme activity involved in lipid metabolism in the liver of broilers.

This study aimed to characterize the effects of different dietary forms of supplemental manganese (Mn) on hepatic lipid deposition, gene expression, and enzyme activity in liver fat metabolism in 42-d-old broiler chickens. In total 420 one-day-old Arbor Acres (AA) broilers (rooster:hen = 1:1) were assigned randomly based on body weight and sex to 1 of 6 treatments (10 replicate cages per treatment and 7 broilers per replicate cage) in a completely randomized design using a 2 (sex) × 3 (diet) factorial arrangement. The 3 diets were basal control diets without Mn supplementation and basal diets supplemented with either Mn sulfate or Mn proteinate. No sex × diet interactions were observed in any of the measured indexes; thus, the effect of diet alone was presented in this study. Dietary Mn supplementation increased Mn content in the plasma and liver, adipose triglyceride lipase (ATGL) activity, and ATGL mRNA and its protein expression in the liver by 5.3% to 24.0% (P < 0.05), but reduced plasma triglyceride (TG), total cholesterol, and low-density lipoprotein (LDL-C) levels, liver TG content, fatty acid synthase (FAS) and malic enzyme (ME) activities, mRNA expression of sterol-regulatory element-binding protein 1 (SREBP1), FAS, stearoyl-coA desaturase (SCD), and ME, as well as the protein expression of SREBP1 and SCD in the liver by 5.5% to 22.8% (P < 0.05). No differences were observed between the 2 Mn sources in all of the determined parameters. Therefore, it was concluded that dietary Mn supplementation, regardless of Mn source, decreased hepatic lipid accumulation in broilers by inhibiting SREBP1 and SCD expression, FAS and ME activities, and enhancing ATGL expression and activity.

Dietary manganese supplementation regulates lipid deposition in broiler chickens, with the liver being a significant site of lipid metabolism. This study investigated the effects of different dietary forms of supplemental manganese on hepatic lipid deposition, gene expression, and enzyme activity in the liver fat metabolism of broiler chickens. The results showed that dietary manganese supplementation decreased the hepatic lipid accumulation of broilers by inhibiting the expression of sterol-regulatory element-binding protein 1 (SREBP1) and stearoyl-coA desaturase (SCD), as well as fatty acid synthase (FAS) and malic enzyme (ME) activities, and enhancing the expression and activity of adipose triglyceride lipase (ATGL). This reduction in excessive fat production will help improve poultry health and mitigate losses in the poultry industry.

A new mechanism of respiratory syncytial virus entry inhibition by small-molecule to overcome K394R-associated resistance.

Infection with respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract disease in young children and older people. Despite intensive efforts over the past few decades, no direct-acting small-molecule agents against RSV are available. Most small-molecule candidates targeting the RSV fusion (F) protein pose a considerable risk of inducing drug-resistant mutations. Here, we explored the in vitro and in vivo virological properties of the K394R variant, a cross-resistant mutant capable of evading multiple RSV fusion inhibitors. Our results demonstrated that the K394R variant is highly fusogenic in vitro and more pathogenic than the parental strain in vivo. The small molecule (2E,2'E)-N,N'-((1R,2S,3S)-3-hydroxycyclohexane-1,2-diyl)bis(3-(2-bromo-4-fluorophenyl) acrylamide) (CL-A3-7), a structurally optimized compound derived from a natural caffeoylquinic acid derivative, substantially reduced in vitro and in vivo infections of both wild-type RSV and the K394R variant. Mechanistically, CL-A3-7 significantly inhibited virus-cell fusion during RSV entry by blocking the interaction between the viral F protein and the cellular insulin-like growth factor 1 receptor (IGF1R). Collectively, these results indicate severe disease risks caused by the K394R variant and reveal a new anti-RSV mechanism to overcome K394R-associated resistance. IMPORTANCE: Respiratory syncytial virus (RSV) infection is a major public health concern, and many small-molecule candidates targeting the viral fusion (F) protein are associated with a considerable risk of inducing drug-resistant mutations. This study investigated virological features of the K394R variant, a mutant strain conferring resistance to multiple RSV fusion inhibitors. Our results demonstrated that the K394R variant is highly fusogenic in cell cultures and more pathogenic than the parental strain in mice. The small-molecule inhibitor CL-A3-7 substantially reduced in vitro and in vivo infections of both wild-type RSV and the K394R variant by blocking the interaction of viral F protein with its cellular receptor, showing a new mechanism of action for small-molecules to inhibit RSV infection and overcome K394R-associated resistance.

Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health. Therefore, this study examined patients who underwent breast cancer surgery, analyzed hospitalization costs and structure, and explored the impact of China Healthcare Security Diagnosis Related Groups (CHS-DRG) management on patient costs. It aimed to provide medical institutions with ways to reduce costs, optimize cost structures, reduce patient burden, and improve service efficiency. AIM: To study the CHS-DRG payment system's impact on breast cancer surgery costs. METHODS: Using the CHS-DRG (version 1.1) grouping criteria, 4073 patients, who underwent the radical resection of breast malignant tumors from January to December 2023, were included in the JA29 group; 1028 patients were part of the CHS-DRG payment system, unlike the rest. Through an independent sample t-test, the length of hospital stay as well as total hospitalization, medicine and consumables, medical, nursing, medical technology, and management expenses were compared. Pearson's correlation coefficient was used to test the cost correlation. RESULTS: In terms of hospitalization expenses, patients in the CHS-DRG payment group had lower medical, nursing, and management expenses than those in the diagnosis-related group (DRG) non-payment group. For patients in the DRG payment group, the factors affecting the total hospitalization cost, in descending order of relevance, were medicine and consumable costs, consumable costs, medicine costs, medical costs, medical technology costs, management costs, nursing costs, and length of hospital stay. For patients in the DRG non-payment group, the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses, consumable expenses, medical technology expenses, the cost of medicines, medical expenses, nursing expenses, length of hospital stay, and management expenses. CONCLUSION: The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs, medical consumable costs, and the length of hospital stay while ensuring medical safety.