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BackgroundTechnical capabilities for performing liver transplantation have developed rapidly; however, the lack of available livers has prompted the utilization of edge donor grafts, including those donated after circulatory death, older donors, and hepatic steatosis, thereby rendering it difficult to define optimal clinical outcomes. ObjectiveWe aimed to investigate the efficacy of telemedicine for follow-up management after liver transplantation. MethodsTo determine the efficacy of telemedicine for follow-up after liver transplantation, we performed a clinical observation cohort study to evaluate the rate of recovery, readmission rate within 30 days after discharge, mortality, and morbidity. Patients (n=110) who underwent liver transplantation (with livers from organ donation after citizen's death) were randomly assigned to receive either telemedicine-based follow-up management for 2 weeks in addition to the usual care or usual care follow-up only. Patients in the telemedicine group were given a robot free-of-charge for 2 weeks of follow-up. Using the robot, patients interacted daily, for approximately 20 minutes, with transplant specialists who assessed respiratory rate, electrocardiogram, blood pressure, oxygen saturation, and blood glucose level; asked patients about immunosuppressant medication use, diet, sleep, gastrointestinal function, exercise, and T-tube drainage; and recommended rehabilitation exercises. ResultsNo differences were detected between patients in the telemedicine group (n=52) and those in the usual care group (n=50) regarding age (P=.17), the model for end-stage liver disease score (MELD, P=.14), operation time (P=.51), blood loss (P=.07), and transfusion volume (P=.13). The length and expenses of the initial hospitalization (P=.03 and P=.049) were lower in the telemedicine group than they were in the usual care follow-up group. The number of patients with MELD score ≥30 before liver transplantation was greater in the usual care follow-up group than that in the telemedicine group. Furthermore, the readmission rate within 30 days after discharge was markedly lower in the telemedicine group than in the usual care follow-up group (P=.02). The postoperative survival rates at 12 months in the telemedicine group and the usual care follow-up group were 94.2% and 90.0% (P=.65), respectively. Warning signs of complications were detected early and treated in time in the telemedicine group. Furthermore, no significant difference was detected in the long-term visit cumulative survival rate between the two groups (P=.50). ConclusionsRapid recovery and markedly lower readmission rates within 30 days after discharge were evident for telemedicine follow-up management of patients post–liver transplantation, which might be due to high-efficiency in perioperative and follow-up management. Moreover, telemedicine follow-up management promotes the self-management and medication adherence, which improves patients’ health-related quality of life and facilitates achieving optimal clinical outcomes in post–liver transplantation.

Argonaute proteins (Agos) represent a highly conserved family of proteins prevalent in all domains of life and have been implicated in various biological processes. Based on the domain architecture, Agos can be divided into long Agos and short Agos. While long Agos have been extensively studied over the past two decades, short Agos, found exclusively in prokaryotes, have recently gained attention for their roles in prokaryotic immune defence against mobile genetic elements, such as plasmids and phages. Notable functional and structural studies provide invaluable insights into the underlying molecular mechanisms of representative short Ago systems. Despite the diverse domain arrangements, short Agos generally form heterodimeric complexes with their associated effector proteins, activating the effector’s enzymatic activities upon target detection. The activation of effector proteins in the short Ago systems leads to bacterial cell death, a mechanism of sacrificing individuals to protect the community.

ObjectiveThis study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy.Materials and MethodsClinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value.ResultsCompared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms.ConclusionThe CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.

Abstract Background Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. Material and methods Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (μCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1β, IL-4). Results Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1β levels, and less active MMP-9 in cell culture. Conclusion This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

Real-world memories are formed in a particular context and are often not acquired or recalled in isolation1-5. Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not1-4. How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12-24 h) increase in the expression of C-C chemokine receptor type 5 (CCR5)-an immune receptor that is well known as a co-receptor for HIV infection6,7-after the formation of a contextual memory determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed expression of CCR5 in mouse dorsal CA1 neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and therefore closes the temporal window for memory linking. Our findings also show that an age-related increase in the neuronal expression of CCR5 and its ligand CCL5 leads to impairments in memory linking in aged mice, which could be reversed with a Ccr5 knockout and a drug approved by the US Food and Drug Administration (FDA) that inhibits this receptor, a result with clinical implications. Altogether, the findings reported here provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.

BackgroundVascular dementia (VaD) is the accumulation of vascular lesions in the subcortical white matter of the brain. These lesions progress and there is no direct medical therapy.AimsTo determine the specific cellular responses in VaD so as to provide molecular targets for therapeutic development.Materials and methodsSingle-nucleus transcriptome analysis was performed in human periventricular white matter (PVWM) samples of VaD and normal control (NC) subjects.ResultsDifferential analysis shows that cell type-specific transcriptomic changes in VaD are associated with the disruption of specific biological processes, including angiogenesis, immune activation, axonal injury and myelination. Each cell type in the neurovascular unit within white matter has a specific alteration in gene expression in VaD. In a central cell type for this disease, subcluster analysis of endothelial cells (EC) indicates that VaD contains a disease-associated EC subcluster that expresses genes associated with programmed cell death and a response to protein folding. Two other subpopulations of EC in VaD express molecular systems associated with regenerative processes in angiogenesis, and in axonal sprouting and oligodendrocyte progenitor cell maturation.ConclusionThis comprehensive molecular profiling of brain samples from patients with VaD reveals previously unknown molecular changes in cells of the neurovascular niche, and an attempt at regeneration in injured white matter.

Abstract Background The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. Methods A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. Results In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. Conclusions Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Abstract Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI. Apobec-1 knockout (KO) mice exhibited greater mortality than in wild type (WT) and more severe AKI in both CP- and unilateral ischemia reperfusion (IR) with nephrectomy. Specifically, plasma creatinine (pCr) 2.6 ± 0.70 mg/dL for KO, n = 10 and 0.16 ± 0.02 for WT, n = 6, p

Objective The polishing effects of different compositions of chairside polishing systems on polyetheretherketone (PEEK) were compared to provide a reference for the rational selection of polishing systems for this material in clinical settings. Methods A total of 108 specimens were made from ShushijieTMPEEK crown and bridge materials, Bio-PAEK® dental PEEK, and BioHPP® PEEK. Thirty-six specimens of each material were randomly divided into 6 groups on average based on their polishing technique: OptiDisc®, Super-Snap® Rainbow Technique Kit, VITA ENAMIC®Clinical Polishing Set, Sof-LexTM Diamond Polishing System, Visio.lign Finishing Kit for Composite Veneers, and CERAMAGE Polishing Kit, LavaTM Ultimate ceramic and VITA ENAMIC ceramics were set as the control groups, and 6 specimens were made in each material, polished by Sof-LexTM Diamond Polishing System and VITA ENAMIC® Polishing Set clinical, respectively, according to the manufacturers’ suggestions. The surface roughness (Ra value and Sa value) and gloss of each set were measured. The surface morphologies of the polished specimens were observed by scanning electron microscopy. Results Surface roughness (Ra value and Sa value) and gloss were mainly influenced by the type of polishing system, and they varied between PEEK material types. The Sof-LexTM Diamond Polishing System produced the highest surface roughness and the lowest gloss values for PEEK materials, while the Super-Snap® Rainbow Technique Kit, Visio.lign Finishing Kit for Composite Veneers and CERAMAGE Polishing Kit resulted in low surface roughness values. The Visio.lign Finishing Kit for Composite Veneers and CERAMAGE Polishing Kit exhibited high gloss values. Polishing paste particles were observed embedded on the surfaces of the PEEK materials polished by the Visio.lign Finishing Kit for Composite Veneers; the surfaces of specimens polished by the CERAMAGE Polishing Kit were smooth, without polishing paste particle residue. Using the same polishing system, the best polishing results were obtained with BioHPP® among the PEEK materials tested. The surface roughness values of the three tested PEEK materials polished by the CERAMAGE Polishing Kit were similar to those of the LavaTM Ultimate ceramic and VITA ENAMIC ceramic, but the gloss was higher than that of both. Conclusion CERAMAGE Polishing Kit was recommended for polishing all three tested PEEK materials, achieving a good polishing effect, with similar surface roughness and higher gloss characteristics comparable to those of polished computer-aided design and manufacturing (CAD/CAM) resin-matrix ceramics.