Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Background: Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Methods: Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines and induced pluripotent stem cell-derived dopaminergic neurons and assessed lysosomal activity and the handling of aggregated synuclein fibrils. Results: We first identified specific non-coding variants in CTSB that drive the association with PD and are linked to changes in brain CTSB expression levels. Using iPSC-derived dopaminergic neurons we then find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. Moreover, in cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. Similarly, in midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition or knockout potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. Conclusions: The results of our genetic and functional studies indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

Real-world application of nirmatrelvir/ritonavir in hospitalized COVID-19 patients with onset of symptoms beyond 5 days: a comparative study.

PURPOSE: Physicians may administer Nirmatrelvir-ritonavir to patients who have been symptomatic for more than 5 days. There is currently no clear evidence to support this approach. METHODS: A real-world study was conducted to investigate the potential relationship between the administration of Nirmatrelvir-ritonavir and the rates of intubation or in-hospital mortality among COVID-19 patients who experienced symptoms for more than 5 days. The end point was a composite event of intubation or in-hospital mortality. The outcomes between those patients who received Nirmatrelvir-ritonavir and those who did not were compared. RESULTS: A total of 847 patients were included in the analysis. Among them, 312 patients (36.84%) received Nirmatrelvir-ritonavir. Within the entire population, 86 patients (10.15%) experienced intubation or in-hospital mortality. The main analysis indicated that there was a significant association between the application of Nirmatrelvir-ritonavir and intubation or in-hospital mortality, with an odds ratio of 0.50 (95% confidence interval, 0.28 to 0.87; P = 0.0153) using inverse probability of treatment weighting. The finding was consistent with multiple sensitivity analyses. CONCLUSIONS: The application of Nirmatrelvir-ritonavir was associated with a significantly reduced risk of intubation or death in hospitalized COVID-19 patients who experienced symptoms for more than 5 days as compared to those who did not receive the treatment.

Prediction of all-cause death and specific causes of death in patients with gastric cancer with liver metastasis: a Surveillance, Epidemiology, and End Results-based study.

BACKGROUND: Gastric cancer (GC), considered the fifth most prevalent malignancy, is the fourth leading cause of cancer death worldwide. This cancer is heterogeneous and invasive and often metastasizes to the liver. The survival of patients with GC, especially cancer-specific survival (CSS), is a matter of concern to their families and medical workers in clinical practice. However, efficient tools for early risk prediction are lacking. Thus, this study aimed to develop a nomogram for forecasting the overall survival (OS) and CSS of patients with GC with liver metastasis (GCLM) based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Information on individuals with GCLM was acquired from the SEER database from January 2000 to December 2015. Patients' data were randomized into the train cohort and the test cohort. The independent factors for CSS and OS were determined by univariate and multivariate competing risk analyses and Cox proportional hazards analysis, and the nomograms for predicting CSS and OS were constructed. The receiver operating characteristic curve and calibration curve were used to measure the accuracy and calibration of nomograms. RESULTS: Our study included 4372 patients with GCLM, with 3060 patients in the train set and 1312 in the test set. The mean follow-up period was 12.31 months. The independent factors influencing the OS of patients with GCLM were age, bone metastasis, chemotherapy, grade, lung metastasis, stage, primary site, radiotherapy, surgical primary site, T stage, and tumor size. The concordance Index (C-index) of the constructed nomogram for OS were 0.718 (SE, 0.004) in the train set and 0.0.680 (SE, 0.006) in the test set. The independent factors affecting the CSS of patients with GCLM were age, chemotherapy, grade, lung metastasis, stage, radiotherapy, regional lymph node positive, surgical primary site, and total number of tumors. The C-index for the constructed nomogram for CSS were 0.696 (SE, 0.005) in the train set and 0.696 (SE, 0.008) in the test set. CONCLUSION: The constructed nomograms showed satisfactory performance in predicting the OS and CSS of patients with GCLM, which can help clinicians formulate follow-up and rehabilitation strategies conducive to survival. At the same time, it can provide more family and social support for high-risk groups.

Polymetal-Chelated Fabrication of Bimetallic Nanophosphides as Electrocatalysts for Zinc-Air Batteries.

Bimetallic phosphides are considered as promising electrocatalysts for zinc-air batteries toward oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). To address the semi-conductor inherent low electronic conductivity and catalytic activity, a polymetal-chelated strategy is employed to in situ fabricate bimetallic nanophosphides within carbon matrix anchoring by chemical bonding. The employment of biomolecule polydopamine (PDA) efficiently anchors various transition metal ions due to its strong chelating capability via inherent functional groups. Furthermore, the chelation of multi-metal ion is proved to promote the formation of graphitic nitrogen. The bimetallic FexCoyP phosphides nanoparticles are intimately encapsulated in carbon matrix through in situ carbonization and phosphatization processes. When utilized in Zinc-air batteries, Fe0.20Co0.80P anchored within N, P co-doped sub-microsphere (Fe0.20Co0.80P /PNC) exhibit a maximum power density of 167 mW cm-2 and cycle life up to 270 cycles, with a round-trip voltage of 0.955 V. The mechanisms for catalytic activity passivation are ascribed to the etching of nitrogen and oxidation of phosphorus in carbon matrix, as well as the oxidation of the surface phosphide on the sub-microspheres. This study presents a promising candidate for advancing the further development of energy conversation catalysis.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review.

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.

Precise detection of awareness in disorders of consciousness using deep learning framework.

Diagnosis of disorders of consciousness (DOC) remains a formidable challenge. Deep learning methods have been widely applied in general neurological and psychiatry disorders, while limited in DOC domain. Considering the successful use of resting-state functional MRI (rs-fMRI) for evaluating patients with DOC, this study seeks to explore the conjunction of deep learning techniques and rs-fMRI in precisely detecting awareness in DOC. We initiated our research with a benchmark dataset comprising 140 participants, including 76 unresponsive wakefulness syndrome (UWS), 25 minimally conscious state (MCS), and 39 Controls, from three independent sites. We developed a cascade 3D EfficientNet-B3-based deep learning framework tailored for discriminating MCS from UWS patients, referred to as "DeepDOC", and compared its performance against five state-of-the-art machine learning models. We also included an independent dataset consists of 11 DOC patients to test whether our model could identify patients with cognitive motor dissociation (CMD), in which DOC patients were behaviorally diagnosed unconscious but could be detected conscious by brain computer interface (BCI) method. Our results demonstrate that DeepDOC outperforms the five machine learning models, achieving an area under curve (AUC) value of 0.927 and accuracy of 0.861 for distinguishing MCS from UWS patients. More importantly, DeepDOC excels in CMD identification, achieving an AUC of 1 and accuracy of 0.909. Using gradient-weighted class activation mapping algorithm, we found that the posterior cortex, encompassing the visual cortex, posterior middle temporal gyrus, posterior cingulate cortex, precuneus, and cerebellum, as making a more substantial contribution to classification compared to other brain regions. This research offers a convenient and accurate method for detecting covert awareness in patients with MCS and CMD using rs-fMRI data.

Machine learning and experimental validation identified autophagy signature in hepatic fibrosis.

Background: The molecular mechanisms of hepatic fibrosis (HF), closely related to autophagy, remain unclear. This study aimed to investigate autophagy characteristics in HF. Methods: Gene expression profiles (GSE6764, GSE49541 and GSE84044) were downloaded, normalized, and merged. Autophagy-related differentially expressed genes (ARDEGs) were determined using the limma R package and the Wilcoxon rank sum test and then analyzed by GO, KEGG, GSEA and GSVA. The infiltration of immune cells, molecular subtypes and immune types of healthy control (HC) and HF were analyzed. Machine learning was carried out with two methods, by which, core genes were obtained. Models of liver fibrosis in vivo and in vitro were constructed to verify the expression of core genes and corresponding immune cells. Results: A total of 69 ARDEGs were identified. Series functional cluster analysis showed that ARDEGs were significantly enriched in autophagy and immunity. Activated CD4 T cells, CD56bright natural killer cells, CD56dim natural killer cells, eosinophils, macrophages, mast cells, neutrophils, and type 17 T helper (Th17) cells showed significant differences in infiltration between HC and HF groups. Among ARDEGs, three core genes were identified, that were ATG5, RB1CC1, and PARK2. Considerable changes in the infiltration of immune cells were observed at different expression levels of the three core genes, among which the expression of RB1CC1 was significantly associated with the infiltration of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. In the mouse liver fibrosis experiment, ATG5, RB1CC1, and PARK2 were at higher levels in HF group than those in HC group. Compared with HC group, HF group showed low positive area in F4/80, IL-17 and CD56, indicating decreased expression of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. Meanwhile, knocking down RB1CC1 was found to inhibit the activation of hepatic stellate cells and alleviate liver fibrosis. Conclusion: ATG5, RB1CC1, and PARK2 are promising autophagy-related therapeutic biomarkers for HF. This is the first study to identify RB1CC1 in HF, which may promote the progression of liver fibrosis by regulating macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell.

Mechanically Adaptive Polymers Constructed from Dynamic Coordination Equilibria.

Designing materials capable of adapting their mechanical properties in response to external stimuli is the key to preventing failure and extending their service life. However, existing mechanically adaptive polymers are hindered by limitations such as inadequate load-bearing capacity, difficulty in achieving reversible changes, high cost, and a lack of multiple responsiveness. Herein, we address these challenges using dynamic coordination bonds. A new type of mechanically adaptive material with both rate- and temperature-responsiveness was developed. Owing to the stimuli-responsiveness of the coordination equilibria, the prepared polymers, PBMBD-Fe and PBMBD-Co, exhibit mechanically adaptive properties, including temperature-sensitive strength modulation and rate-dependent impact hardening. Benefitting from the dynamic nature of the coordination bonds, the polymers exhibited impressive energy dissipation, damping capacity (loss factors of 1.15 and 2.09 at 1.0 Hz), self-healing, and 3D printing abilities, offering durable and customizable impact resistance and protective performance. The development of impact-resistant materials with comprehensive properties has potential applications in the sustainable and intelligent protection fields.

Comparison of diagnostic efficacy between 99mTc-methylene diphosphate SPECT/CT and MRI for bone and joint infections: a multicenter retrospective analysis.

Objective: There is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI. Methods: In this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis. Results: Only SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively. Conclusion: This represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

Germline pathogenic variants associated with triple-negative breast cancer in US Hispanic and Guatemalan women using hospital and community-based recruitment strategies.

PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

Postoperative haemoglobin and anaemia-associated ischaemic events after major noncardiac surgery: A sex-stratified cohort study.

STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.

Synergistic Effect of Co-Mo Pinning in Lay-Structured Oxide Cathode for Enhancing Stability toward Potassium-Ion Batteries.

Owing to the high economic efficiency and energy density potential, manganese-based layer-structured oxides have attracted great interests as cathode materials for potassium ion batteries. In order to alleviate the continuous phase transition and K+ re-embedding from Jahn-Teller distortion, the [Mn-Co-Mo]O6 octahedra are introduced into P3-K0.45 MnO2 herein to optimize the local electron structure. Based on the experimental and computational results, the octahedral center metal molybdenum in [MoO6 ] octahedra proposes a smaller ionic radius and higher oxidation state to induce second-order JTE (pseudo-JTE) distortion in the adjacent [MnO6 ] octahedra. This distortion compresses the [MnO6 ] octahedra along the c-axis, leading to an increased interlayer spacing in the K+ layer. Meanwhile, the Mn3+ /Mn4+ is balanced by [CoO6 ] octahedra and the K+ diffusion pathway is optimized as well. The proposed P3-K0.45 Mn0.9 Co0.05 Mo0.05 O2 cathode material shows an enhanced cycling stability and rate performance. It demonstrates a high capacity of 80.2 mAh g-1 at 100 mAh g-1 and 77.3 mAh g-1 at 500 mAh g-1 . Furthermore, it showcases a 2000 cycles stability with a 59.6% capacity retention. This work presents a promising solution to the challenges faced by manganese-based layered oxide cathodes and offers a deep mechanism understanding and improved electrochemical performance.

Insights into the mechanisms and structure of breakage-fusion-bridge cycles in cervical cancer using long-read sequencing.

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cancer cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and our study applies long-read sequencing to this important chromosomal rearrangement type. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes, and only one BFB breakpoint showed chromothripsis. Five cell lines have a chromosomal region 11q BFB event, with YAP1-BIRC3-BIRC2 amplification. Indeed, YAP1 amplification is associated with a 10-year-earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that individuals with cervical cancer and YAP1-BIRC3-BIRC2 amplification, especially those of African ancestry, might benefit from targeted therapy. In summary, we uncovered valuable insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.

Fluoride Doping Na3 Al2/3 V4/3 (PO4 )3 Microspheres As Cathode Materials for Sodium-Ion Batteries with Multielectron Redox.

Sodium-ion batteries (SIBs) are potential candidates for large energy storage usage because of the natural abundance and cheap sodium. Nevertheless, improving the energy density and cycling steadiness of SIB cathodes remains a challenge. In this work, F-doping Na3 Al2/3 V4/3 (PO4 )3 (NAVP) microspheres (Na3 Al2/3 V4/3 (PO4 )2.9 F0.3 (NAVPF)) are synthesized via spray drying and investigated as SIB cathodes. XRD and Rietveld refinement reveal expanded lattice parameters for NAVPF compared to the undoped sample, and the successful cation doping into the Na superionic conductor (NASICON) framework improves Na+ diffusion channels. The NAVPF delivers an ultrahigh capacity of 148 mAh g-1 at 100 mA g-1 with 90.8% retention after 200 cycles, enabled by the activation of V2+ /V5+ multielectron reaction. Notably, NAVPF delivers an ultrahigh rate performance, with a discharge capacity of 83.6 mAh g-1 at 5000 mA g-1 . In situ XRD demonstrates solid-solution reactions occurred during charge-discharge of NAVPF without two-phase reactions, indicating enhanced structural stability after F-doped. The full cell with NAVPF cathode and Na+ preintercalated hard carbon anode shows a large discharge capacity of 100 mAh g-1 at 100 mA g-1 with 80.2% retention after 100 cycles. This anion doping strategy creates a promising SIB cathode candidate for future high-energy-density energy storage applications.

A network pharmacology method explores the molecular mechanism of Coptis chinensis for the treatment of Alzheimer's disease.

To predict the molecular mechanisms of action of Coptis chinensis in the treatment of Alzheimer's disease using network pharmacology. The active ingredients and targets of Coptis chinensis were obtained from the Traditional Chinese Medicine System Pharmacology Database. Target information for Alzheimer's disease was screened using the GeneCard and OMIM databases. The Venn diagram tool was used to identify the intersecting targets of Coptis chinensis and Alzheimer's disease. The obtained target information was entered into the STRING database to construct a protein-protein interaction network. The R language was used to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of significant targets. Auto Dock Vina software was used for molecular docking. Fourteen effective active ingredients and 158 key targets associated with Coptis chinensis were identified. There were 1113 targets related to Alzheimer's disease genes. A drug-component-disease-target network was constructed and 84 key targets were identified for the treatment of Alzheimer's disease by Coptis chinensis. The main signaling pathways were the PI3K-Akt, AGE-RAGE, MAPK, HIF-1, TNF, and relaxin signaling pathways. The molecular docking results showed that berberine has a high affinity for Alzheimer's Disease. Coptis chinensis could play a multi-target and multi-pathway role against Alzheimer's disease, which has guiding significance for clinical research.

Ambient Electrochemical Ammonia Synthesis: From Theoretical Guidance to Catalyst Design.

Ammonia, a vital component in the synthesis of fertilizers, plastics, and explosives, is traditionally produced via the energy-intensive and environmentally detrimental Haber-Bosch process. Given its considerable energy consumption and significant greenhouse gas emissions, there is a growing shift toward electrocatalytic ammonia synthesis as an eco-friendly alternative. However, developing efficient electrocatalysts capable of achieving high selectivity, Faraday efficiency, and yield under ambient conditions remains a significant challenge. This review delves into the decades-long research into electrocatalytic ammonia synthesis, highlighting the evolution of fundamental principles, theoretical descriptors, and reaction mechanisms. An in-depth analysis of the nitrogen reduction reaction (NRR) and nitrate reduction reaction (NitRR) is provided, with a focus on their electrocatalysts. Additionally, the theories behind electrocatalyst design for ammonia synthesis are examined, including the Gibbs free energy approach, Sabatier principle, d-band center theory, and orbital spin states. The review culminates in a comprehensive overview of the current challenges and prospective future directions in electrocatalyst development for NRR and NitRR, paving the way for more sustainable methods of ammonia production.