Magnesium-Mediated Cross-Electrophile Couplings of Aryl 2-Pyridyl Esters with Aryl Bromides for Ketone Synthesis through In Situ-Formed Arylmagnesium Intermediates.

Aryl 2-pyridyl esters could efficiently undergo cross-electrophile couplings with aryl bromides with the aid of magnesium as a reducing metal in the absence of a transition-metal catalyst, leading to the unsymmetrical diaryl ketones in modest to good yields with wide functionality compatibility. In addition, the reaction could be easily scaled up and applied in the late-stage modification of biologically active molecules. Preliminary mechanistic study showed that the coupling reaction presumably proceeds through the in situ formation of arylmagnesium reagents as key intermediates.

Multi-omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single-cell Analysis.

OBJECTIVE: Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in-depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single-cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. METHODS: Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP-counter, and ssGSEA algorithms. Real-time fluorescence quantitative PCR (RT-qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. RESULTS: In OP samples, the proportions of bone marrow-derived mesenchymal stem cells (BM-MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT-qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65-0.90), immature B cells (0.76-0.92), and endothelial cells (0.79-0.87), while showing negative correlations with myeloid-derived suppressor cells (negative 0.54-0.73), T follicular helper cells (negative 0.71-0.86), and natural killer T cells (negative 0.75-0.85). CONCLUSION: Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

Plasmonic Pd-Sb nanosheets for photothermal CH4 conversion to HCHO and therapy.

Photothermal catalysis effectively increases catalytic activity by using the photothermal effect of metal nanomaterials; however, the combination of strong light absorption and high catalytic performance remains a challenge. Here, we demonstrate hexagonal ~5-nanometer-thick palladium antimony (chemical formula as Pd8Sb3) nanosheets (NSs) that exhibit strong light absorption within full spectral and localized surface plasmon resonance (LSPR) effects in the visible region. Such LSPR features lead to strong photothermal effects, and Pd8Sb3 NSs aqueous dispersion enables enhanced photothermal methane (CH4) conversion to formaldehyde (HCHO) under full-spectrum light irradiation at 1.7 watts per square centimeter, leading to selectivity of ~98.7%, productivity of ~665 millimoles per gram of catalyst, ~700 times higher than that of Pd NSs. Mechanism investigations suggest that different radicals were generated on Pd8Sb3 (·OH) and Pd NSs (·O2-), where Pd8Sb3 NSs displays stronger adsorption strength to CH4 and facilitates CH4 oxidation to HCHO. Besides, the strong light absorption ability of Pd8Sb3 NSs enables photothermal therapy for breast cancer.

Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

Melatonin inhibits bovine viral diarrhea virus replication by ER stress-mediated NF-κB signal pathway and autophagy in MDBK cells.

Bovine viral diarrhea-mucosal disease (BVD-MD) is a contagious disease in cattle, caused by the bovine viral diarrhea virus (BVDV). This virus continues to spread globally, exerting pressure on both public health and the economy. Despite its impact, there are currently no effective drugs for treating BVDV. This study utilized Madin-Darby bovine kidney (MDBK) cells as a model to investigate the antiviral effects of melatonin against Bovine Viral Diarrhea Virus (BVDV) and its connection with endoplasmic reticulum (ER) stress. Our results show that melatonin can suppress BVDV proliferation in MDBK cells by modulating the endoplasmic reticulum (ER) stress-mediated NF-κB pathway and autophagy. Specifically, melatonin alleviated ER stress, inhibited the activation of IκBα and p65, regulated autophagy, and reduced the expression levels of pro-inflammatory cytokines. Further, when we treated BVDV-infected cells with the ER stress inducer thapsigargin, it led to significant activation of the NF-κB pathway and autophagy. Conversely, treating the cells with the ER stress inhibitor 4-phenylbutyric acid reversed these effects. These findings suggest that melatonin exerts its antiviral effects primarily through the PERK-eIF2α-ATF4 of ER stress-mediated NF-κB pathway and autophagy. Overall, our study underscores the potential of melatonin as an effective protective and therapeutic option against BVDV, offering insights into its anti-infective mechanisms.

Visible-Light-Promoted and Electron Donor-Acceptor Complex-Driven Double Csp2-H Bond Functionalization of 2-Arylindoles: A Strategy for the Synthesis of Benzo[a]carbazoles.

A green and efficient protocol for the preparation of benzo[a]carbazoles via visible-light-promoted and electron donor-acceptor (EDA) complex-driven intermolecular cyclization of 2-arylindoles with Z-α-bromocinnamaldehydes in the absence of external photocatalysts, transition metals, and oxidants was reported. This new approach demonstrates an intermolecular cyclization model using indole derivatives as electron donors under visible light. Mechanistic investigations have showed that 2-arylindoles with Z-α-bromocinnamaldehydes form EDA complexes, which undergo sequential single-electron transfer, radical coupling, 6π-electrocyclization, and dehydroaromatization to generate benzo[a]carbazoles under visible light irradiation. The current photochemical method features readily accessible starting materials, mild conditions, simple operation, and a broad substrate scope.

A nomogram model for predicting postoperative prognosis in patients with aneurysmal subarachnoid hemorrhage using preoperative biochemical indices.

OBJECTIVE: The nutritional status and inflammatory responses of patients with aneurysmal subarachnoid hemorrhage (aSAH) play a vital prognostic role. We investigated the relationship between preoperative prognostic nutritional index (PNI)、neutrophil/albumin ratio (NAR)、platelet/albumin ratio (PAR) and other factors and the clinical prognosis of patients who underwent clipping for aSAH and its predictive model. METHODS: The clinical data of 212 patients with aSAH who underwent neurosurgery at Nanyang Central Hospital between 2018 and 2023 were retrospectively analyzed. Based on the Glasgow Outcome Scale (GOS) score at 6 months postoperatively, the patients were categorized into two groups: poor (GOSI-III) and good (GOSIV-V) prognosis groups. Multivariate logistic regression analysis was performed to determine the predictive value of preoperative PNI、NAR、PAR、hyperlipidemia and Glasgow Coma Scale (GCS) for prognosis. Furthermore, nomograms and prognostic prediction models were constructed. Receiver operating characteristic curves and area under the curve (AUC) were utilized to determine the predictive values. RESULTS: Multivariate logistic regression analysis revealed that PNI (OR = 1.250, 95%CI 1.060 ~ 1.475, P = 0.008), NAR (OR = 0.000, 95%CI 0.000 ~ 0.004, P = 0.000), PAR(OR = 0.515, 95%CI 0.283 ~ 0.937, P = 0.030), hyperlipidemia (OR = 4.627, 95%CI 1.166 ~ 18.367, P = 0.029), and GCS(OR = 1.446, 95%CI 1.041 ~ 2.008, P = 0.028) are independent risk factors for poor postoperative prognosis. The total score of the nomogram was 200, and the AUC value was 0.972. CONCLUSIONS: PNI and NAR can reflect the nutritional status and inflammatory responses of patients.They are significantly associated with the postoperative prognosis of patients with aSAH. Comprehensively analyzing PNI and NAR combined with other clinical indicators can more effectively guide treatment and help predict prognosis.

A sarcomatoid malignancy originating in the right cervical lymph nodes with atypical pathological characteristics: a case report of an incidental finding.

Background: Primary malignancies of the cervical lymph nodes with special pathological characteristics are relatively uncommon in clinical settings, and there have been few reports on these tumors. The precise basis for their pathogenesis is poorly understood, and their diagnosis can be challenging. In addition, no clinically validated treatments have been established to date for affected patients. Case Description: Here, we describe a case of a 65-year-old male patient who exhibited the enlargement of several lateral and supraclavicular lymph nodes on the right side of his neck that presented as a large mass associated with a high fever and benign leukocytosis. He did not exhibit any relevant prior history. Radiological assessment revealed that this lesion was the primary tumor and that it has since spread to the liver. Histological assessment was unable to definitively classify the pathological characteristics of this tumor. Without any relevant morphological findings, immunohistochemical outcomes were not sufficiently specific to clarify the origin of these cells. When distinguishing it from similar sarcomas of the lymphohematopoietic system, it was found to not be typical of a histiocytic or dendritic cell tumor. Treatment to this patient was performed following multidisciplinary consultation and consisted of one course of a cyclophosphamide plus doxorubicin, vincristine, and dexamethasone regimen and two courses of the cyclophosphamide plus pirarubicin, vincristine, and dexamethasone regimen. However, the tumor exhibited minimal response to such treatment. While radiotherapy was proposed, the patient lacked confidence in the approach and declined treatment. He eventually developed severe tumor-associated complications. In the discussion section of this report, we detail and analyze the pathogenesis, diagnosis, and referential treatments of this rare malignancy. Conclusions: This is the first report describing such a malignancy, and we hope that the publication of these findings can lead to the recognition of this tumor while supporting efforts to acquire greater experience in the diagnosis and treatment of affected patients.

Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives.

Molecular subtypes play a pivotal role in guiding preclinical and clinical risk assessment and treatment strategies in cancer. In this study, we extracted whole-tissue transcriptomic data from 1,987 ovarian cancer patients spanning 26 independent GEO cohorts. A total of four consensus subtypes (C1-C4) were identified, notably, subtype C1 samples exhibited a poor prognosis and higher M2 macrophages infiltration, whereas subtype C2 samples demonstrated the best prognosis and higher CD4 resting T cells infiltration. Additionally, we characterized cancer- and stromal-specific gene expression profiles, and conducted an analysis of ligand-receptor interactions within these compartments. Based on cancer compartment, subtype-specific interactions as well as gene signatures for each molecular subtype were identified. Leveraging single-cell transcriptomic data, we delineated malignant epithelial cells with four molecular subtypes and observed an increase in C1 cell proportions from primary to relapse to metastasis stages, with a corresponding decrease in C2 cell proportions. Furthermore, we investigated subtype-specific interaction with T cells through integrated analysis of bulk and single-cell datasets. Finally, we developed a robust 10-gene risk model based on subtype gene signatures for prognostic evaluation in ovarian cancer, demonstrating its efficacy across independent datasets. In summary, this study systematically explored ovarian cancer molecular subtypes and provided a framework for other cancer types.

Methane dynamics altered by reservoir operations in a typical tributary of the Three Gorges Reservoir.

Substantial nutrient inputs from reservoir impoundment typically increase sedimentation rate and primary production. This can greatly enhance methane (CH4) production, making reservoirs potentially significant sources of atmospheric CH4. Consequently, elucidating CH4 emissions from reservoirs is crucial for assessing their role in the global methane budget. Reservoir operations can also influence hydrodynamic and biogeochemical processes, potentially leading to pronounced spatiotemporal heterogeneity, especially in reservoirs with complex tributaries, such as the Three Gorges Reservoir (TGR). Although several studies have investigated the spatial and temporal variations in CH4 emissions in the TGR and its tributaries, considerable uncertainties remain regarding the impact of reservoir operations on CH4 dynamics. These uncertainties primarily arise from the limited spatial and temporal resolutions of previous measurements and the complex underlying mechanisms of CH4 dynamics in reservoirs. In this study, we employed a fast-response automated gas equilibrator to measure the spatial distribution and seasonal variations of dissolved CH4 concentrations in XXB, a representative area significantly impacted by TGR operations and known for severe algal blooms. Additionally, we measured CH4 production rates in sediments and diffusive CH4 flux in the surface water. Our multiple campaigns suggest substantial spatial and temporal variability in CH4 concentrations across XXB. Specifically, dissolved CH4 concentrations were generally higher upstream than downstream and exhibited a vertical stratification, with greater concentrations in bottom water compared to surface water. The peak dissolved CH4 concentration was observed in May during the drained period. Our results suggest that the interplay between aquatic organic matter, which promotes CH4 production, and the dilution process caused by intrusion flows from the mainstream primarily drives this spatiotemporal variability. Importantly, our study indicates the feasibility of using strategic reservoir operations to regulate these factors and mitigate CH4 emissions. This eco-environmental approach could also be a pivotal management strategy to reduce greenhouse gas emissions from other reservoirs.

An integrated biorefinery strategy for Eucalyptus fractionation and co-producing glucose, furfural, and lignin based on deep eutectic solvent/cyclopentyl methyl ether system.

A novel biphasic system containing water-soluble deep eutectic solvent (DES) and cyclopentyl methyl ether (CPME) was developed to treat Eucalyptus for furfural production, extracting lignin and enhancing cellulose enzymatic hydrolysis. Herein effect of DES type, water content in DES, temperature and time on furfural yield in water-soluble DES/CPME pretreatment process was firstly evaluated. A maximum furfural yield of 80.6 % was attained in 10 min at 150 °C with choline chloride (ChCl)/citric acid monohydrate (CAM)/CPME system containing 30 wt% water and 2.5 wt% SnCl4·5H2O, which was higher than that obtained from ChCl/CAM/CPME system without water (55.5 %) and H2O/CPME system (49.7 %). These results demonstrated that the water-soluble DES/CPME system was a powerful method enhancing the furfural production. Under the optimal pretreatment conditions, the delignification and glucose yield were reached to 72.7 % and 94.3 %, respectively. The extracted lignin showed low molecular weight and ß-aryl-ether was obviously cleaved. Additionally, water-soluble DES/CPME pretreatment led to a significant removal of hemicelluloses (100.0 %) and lignin (72.7 %) and introduced morphological changes on cell walls, especially from the cell corner (CC) and secondary wall (SW) layers. Overall, this work proposed a practical one-step fractionation strategy for co-producing furfural, lignin and fermentable sugar, providing a way to biorefinery.

Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/ß-catenin pathway modulation to suppress liver cancer.

BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.

Feasibility of noninvasive near-infrared spectroscopy monitoring in predicting the prognosis of spontaneous intracerebral hemorrhage.

Objective: This study aimed to assess the impact of multimodal monitoring on predicting the prognosis of patients with spontaneous intracerebral hemorrhage (SICH) and to examine the feasibility of using noninvasive near-infrared spectroscopy (NIRS) for monitoring clinical prognosis. Methods: Clinical data of 38 patients with SICH who underwent surgery in the Department of Neurosurgery of Shaanxi Provincial People's Hospital from May 2022 to December 2022 were retrospectively analyzed. The patients were categorized into two groups based on the Glasgow Outcome Scale (GOS) 3 months after operation: poor outcome group (GOSI-III) and good outcome group (GOSIV and V). Multimodal monitoring included invasive intracranial pressure (ICP), brain temperature (BT), internal jugular venous oxygen saturation (SjvO2), and noninvasive NIRS. NIRS monitoring comprised the assessment of brain tissue oxygen saturation (StO2), blood volume index (BVI), and tissue hemoglobin index (THI). The prognostic differences between the two groups were compared. The predictive values were evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: ICP, BT, BVI, and THI in the good prognosis group were lower than those in the poor prognosis group. The SjvO2 and StO2 in the group with a good prognosis were higher than those in the group with a poor prognosis. Conclusion: The levels of ICP, BT, SjvO2, StO2, BVI, and THI reflect the changes in brain function and cerebral blood flow and significantly correlate with the prognosis of patients with SICH. NIRS monitoring has a high clinical utility in assessing the prognosis.

Baicalin Plays an Anti-Osteosarcoma Role in Vitro and Promotes Osteogenic Differentiation by Inhibiting NF-κB Signaling.

BACKGROUND: Osteosarcoma (OS) is commonly recognized as a malignant cancer originating from bone-forming mesenchymal stem cells, comprising approximately 20% of sarcomas. Baicalin, a bioactive flavonoid glycoside isolated from Scutellaria baicalensis, has been demonstrated to possess potent anti-inflammatory and neuroprotective properties. OBJECTIVE: To explore the potential mechanisms through which baicalin exerts anti-osteosarcoma effects and facilitates osteogenesis in vitro. METHODS: Cell Counting Kit-8 (CCK-8), scratch assay, and transwell assay were employed to assess the effects of baicalin at varying concentrations (20, 40, and 80 µM) on U2OS cell proliferation, invasion, and migration, respectively. Western blot and qRT-PCR analyses were conducted to evaluate the influence of baicalin on the osteogenic potential of OS cells by examining osteoblast markers such as osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), as well as the osteoclast marker-receptor activator of nuclear factor kappa B ligand (RANKL). Additionally, the impact of baicalin on epithelial-mesenchymal transition (EMT) markers (N-cadherin, E-cadherin, Vimentin) and proteins related to the Nuclear factor κB (NF-κB) signaling pathway (p-p65, p-IκBα, p65, IκBα) in OS cells was evaluated via western blot analysis. The activity and mineralization capacity of Alkaline Phosphatase (ALP) in baicalin-treated cells were examined through ALP staining and Alizarin Red S (ARS) staining. RESULTS: Baicalin exhibited significant suppression of OS cell U2OS invasion (p < 0.01), migration (p < 0.01), and proliferation (p < 0.05) at various concentrations. Additionally, baicalin treatment notably increased the E-cadherin protein level, while decreasing the expression levels of Vimentin and N-cadherin proteins (p < 0.01), thus promoting EMT. Following baicalin treatment, there was a marked elevation in the protein and mRNA expression levels of RUNX2, OPN, and OCN, while the expression level of RANKL protein was reduced (p < 0.05), indicating enhanced osteogenic differentiation. The groups treated with baicalin exhibited higher ALP activity and mineralization ability (p < 0.01). Moreover, baicalin treatment significantly reduced the expression levels of p-IκBα and p-p65 proteins, as well as the ratios of p-IκBα/IκBα and p-p65/p65 (p < 0.01). These effects of baicalin were concentration-dependent, with higher concentrations yielding stronger effects. CONCLUSION: In vitro, baicalin demonstrates anti-OS effects and facilitates osteogenic differentiation, potentially by inhibiting NF-κB pathway activity.

Identification and characterization of linear epitopes of monoclonal antibodies against the capsid proteins of small ruminant lentiviruses.

Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) are members of a group of genetically highly homologous lentiviruses collectively referred to as small ruminant lentiviruses (SRLVs). SRLVs can infect sheep, goats and other small ruminants, causing multisystemic disease with progressive and persistent inflammatory changes, severely reducing animal productivity and impeding animal trade. The capsid protein of SRLVs, p28, is highly conserved among strains and is a commonly used marker for the detection of SRLVs. In this study, two monoclonal antibodies (mAbs), designated G8F7 and A10C12, against p28 were generated using a recombinant p28 protein expressed in Escherichia coli as an immunogen. Functional analysis showed that these two monoclonal antibodies could be used in iELISA, immunofluorescence assays (IFA) and western blot assays to detect p28 or Gag precursor proteins of SRLVs. Two linear epitopes, 61GNRAQKELIQGKLNEEA77 (E61-77) and 187CQKQMDRVLGTRVQQATVEEKMQACR212 (E187-212), which are recognized by G8F7 and A10C12, respectively, were identified through truncation of the GST-fused p28. Amino acid sequence alignment showed that the epitope E61-77 is conserved among SRLVs, with a dominant mutation site (K72R) that does not disrupt recognition by G8F7. E187-212 was found to exhibit variability among SRLVs, but the majority of mutant epitopes are recognized by A10C12, with the exception of a mutant epitope from an isolate with undefined subtypes from Ovis aries, which was not recognized. These findings may facilitate future study of SRLVs and promote the development of methods for the detection of these viruses.

Clinical application of mixed reality holographic imaging technology in scaling and root planing of severe periodontitis: a proof of concept.

OBJECTIVES: To demonstrate the potential application of mixed reality (MR) holographic imaging technology in subgingival scaling and root planing (SRP) for patient with advanced periodontitis. METHODS: This case series comprised the analysis of 1566 sites from 261 teeth of 10 patients with advanced periodontitis. Digital CBCT scans and intraoral scans of the patients were digitally acquired preoperatively and aligned to create a three-dimensional periodontal visualization model. Through rendering, interactive holographic images were displayed using MR. The surgeon first used MR images to communicate with the patients, and then facilitated SRP under their guidance. Probing pocket depth (PPD), clinical attachment loss (CAL), Plaque index (PI), and bleeding on probing (BOP) parameters were recorded at baseline and at 8-week postoperatively. Patient-reported outcome indicator questionnaires on self-efficacy were also collected. RESULTS: PPD, CAL, PI, and BOP significantly decreased at 8-week following MR hologram-assisted SRP (p<0.001). For sites with PPD≥4 mm, PPD and CAL declined by 2.33±1.23 mm and 0.69±1.07 mm, respectively. PI significantly decreased from 1.94±0.61 to 0.82±0.58 (p < 0.001) and BOP sites decreased significantly from 84.11% to 40.25%. After receiving MR holograms for condition communication, most patients had a better perception of the effectiveness of SRP treatment and the benefits it brings. 80% of the subjects expressed their willingness to undergo MR-assisted periodontal treatment in the future. CONCLUSION: These results provide preliminary support for MR hologram-assisted digital SRP. With this technology, images of the gingiva and alveolar bone can be displayed in real time, accurately and three-dimensionally. This improves SRP effectiveness, diminishes complications, and enhances patients' confidence in the treatment. CLINICAL SIGNIFICANCE: MR holographic imaging-based digital SRP is a clinically feasible and promising adjunctive periodontal treatment option. It may contribute to improved non-surgical treatment efficacy in patients with severe periodontitis.

Electrooxidative 1,3-Oxo/Carboamination of Arylcyclopropanes.

Herein, the work demonstrates an electrochemically paired electrolysis approach facilitating the efficient achievement of the electrooxidative 1,3-oxo/carboamination of arylcyclopropanes under mild conditions. The formation of 1,3-arylamination of arylcyclopropanes involves commercially available amine redox mediators through a radical-radical process. In addition, the successful execution of ß-amino ketones also occurs under atmospheric conditions. The control experiments supported the existence of key benzylic radical intermediates in the reaction pathway.

Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure.

Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.

Highly dispersed noble metal nanoparticle composites on biomass-derived carbon-based carriers: synthesis, characterization, and catalytic applications.

Precious metal nanoparticles have been widely investigated due to their excellent activity shown in catalysis and sensing. However, how to prepare highly dispersed noble metal nanoparticles to improve the lifetime of catalysts and reduce the cost is still an urgent problem to be solved. In this study, a carbon-based carrier material was prepared by an expansion method and loaded with Pd or Ag nanoparticles on this carbon material to synthesize precious metal nanoparticle composites, which were characterized in detail. The results show that the nanoparticles prepared using this method exhibit superior dispersion. Under the synergistic effect of noble metal nanoparticles and porous carbon carriers, the composites exhibited excellent catalytic degradation of p-nitrophenol and showed excellent sensing performance in the modified hydrogen peroxide sensor electrode. This approach is highly informative for the preparation of nanocomposites in medical and environmental fields.

Feasibility and safety of ultrasound-guided percutaneous transhepatic measurement of portal venous pressure.

BACKGROUND AND OBJECTIVE: The measurement of portal venous pressure (PVP) has been extensively studied, primarily through indirect methods. However, the potential of ultrasound-guided percutaneous transhepatic PVP measurement as a direct method has been largely unexplored. This study aimed to investigate the accuracy, safety, and feasibility of this approach. METHODS: In vitro, the experiment aimed to select a needle that could accurately transmit pressure, had a small inner diameter and was suitable for liver puncture, and performed on 20 healthy New Zealand white rabbits. An ultrasound-guided percutaneous transhepatic portal vein puncture was undertaken to measure PVP. Additionally, free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP) were measured under digital subtraction angiography (DSA). The correlation between the two methods was assessed. Enroll study participants from October 18, 2023 to November 11, 2023 with written informed consent. Five patients were measured the PVP under ultrasound guidance before surgery to determine the feasibility of this measurement method. RESULTS: There was no significant difference in the results obtained using 9 different types of needles (P > 0.05). This demonstrated a great repeatability (P < 0.05). The 22G chiba needle with small inner diameter, allowing for accurate pressure transmission and suitable for liver puncture, was utilized for percutaneous transhepatic PVP measurement. There were positive correlations between PVP and HVPG (r = 0.881), PVP and WHVP (r = 0.709), HVPG and WHVP (r = 0.729), IVCP and FHVP (r = 0.572). The PVP was accurately and safely measured in 5 patients with segmental hepatectomy. No complications could be identified during postoperative ultrasound. CONCLUSION: Percutaneous transhepatic portal venous puncture under ultrasound guidance is accurate, safe and feasible to measure portal venous pressure. CLINICAL TRIAL REGISTRATION NUMBER: This study has been registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300076751.