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Abstract Background Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”‐penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post‐assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre‐intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7‐day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”‐penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial‐related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion This study found that these experimental data indicated that SA at “Baihui”‐penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

Abstract Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.

Abstract Background Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines. Results We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history. Conclusions Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy. Graphical Abstract

To meet the growing emission of water contaminants, the development of new materials that enhance the efficiency of the water treatment system is urgent. Ordered mesoporous materials provide opportunities in environmental processing applications due to their exceptionally high surface areas, large pore sizes, and enough pore volumes. These properties might enhance the performance of materials concerning adsorption/catalysis capability, durability, and stability. In this review, we enumerate the ordered mesoporous materials as adsorbents/catalysts and their modifications in water pollution treatment from the past decade, including heavy metals (Hg2+, Pb2+, Cd2+, Cr6+, etc.), toxic anions (nitrate, phosphate, fluoride, etc.), and organic contaminants (organic dyes, antibiotics, etc.). These contributions demonstrate a deep understanding of the synergistic effect between the incorporated framework and homogeneous active centers. Besides, the challenges and perspectives of the future developments of ordered mesoporous materials in wastewater treatment are proposed. This work provides a theoretical basis and complete summary for the application of ordered mesoporous materials in the removal of contaminants from aqueous solutions.

Background: Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. Methods: From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. Results: Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7–6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). Conclusion: ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

Abstract Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell–cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.

Affective data is the basis of emotion recognition, which is mainly acquired through extrinsic elicitation. To investigate the enhancing effects of multi-sensory stimuli on emotion elicitation and emotion recognition, we designed an experimental paradigm involving visual, auditory, and olfactory senses. A multimodal emotional dataset (OVPD-II) that employed the video-only or video-odor patterns as the stimuli materials, and recorded the electroencephalogram (EEG) and electrooculogram (EOG) signals, was created. The feedback results reported by subjects after each trial demonstrated that the video-odor pattern outperformed the video-only pattern in evoking individuals’ emotions. To further validate the efficiency of the video-odor pattern, the transformer was employed to perform the emotion recognition task, where the highest accuracy reached 86.65% (66.12%) for EEG (EOG) modality with the video-odor pattern, which improved by 1.42% (3.43%) compared with the video-only pattern. What’s more, the hybrid fusion (HF) method combined with the transformer and joint training was developed to improve the performance of the emotion recognition task, which achieved classify accuracies of 89.50% and 88.47% for the video-odor and video-only patterns, respectively.

The large-capacity power flywheel energy storage system serves as a high-quality frequency modulation resource for the power system. Utilizing high-strength, low-density composite materials in the manufacture of flywheel rotors is a primary method for enhancing flywheel energy storage. In this paper, we focus on the large-size multi-ring composite flywheel rotor. Based on the elastic theory, the stress distribution formula of the anisotropic material rotor rim under high-speed rotation is derived. Based on the stress superposition principle, the stress analysis formula under the interference fit of the composite rim and the metal hub is obtained, and the analytical solution is given. Based on the radial displacement of each ring, a suitable amount of interference is determined. Subsequently, a finite element analysis model for the interference fit between the composite rim and the metal hub is established. The stress distribution of the rotor is simulated and analyzed. The simulation results are basically consistent with the analytical results, which verifies the rationality of the model. Finally, we analyze and compare the difference between multi-ring isomorphism and multi-ring isomerism, and then the applicability of the analytical solution and simulation solution to the stress distribution of three-ring and four-ring composite flywheel rotor is further verified. The results demonstrate that, for large-size composite flywheels, existing formula analysis calculations and finite element simulation calculations align, highlighting a need for experimental verification in future research.

The loss of rural kindergarten teachers has become a common social concern in China, which is of great importance to the development of preschool education. This study conducted a survey of 2944 kindergarten teachers in mainland China, to explore the relationship between work–family conflict and turnover intention, the mediating effect of emotional exhaustion, and the moderating effect of professional identity. The study used the work–family conflict questionnaire, the emotional exhaustion scale, the turnover intention questionnaire, and the professional identity questionnaire. The results showed that (1) work–family conflict significantly predicted turnover intention; (2) emotional exhaustion played a mediating role between work–family conflict and turnover intention; and (3) professional identity moderated the latter half path of the mediation model, that is, strong professional identity alleviated the indirect predicting effect of work–family conflict on turnover intention through emotional exhaustion. The results clarified the influencing mechanism of work–family conflict on turnover intention, which could help improve rural preschool teachers’ positive emotions and reducing turnover.

Lamellar bone, compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales, is the structural motif of mature bone. Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone. Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge. Herein, using bioskiving and mineralization, we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone. Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving, the hierarchical mimicry and hierarchy-property relationship are elucidated. With prolongation of mineralization, hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner, i.e. first rising and then descending, which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization. Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis. Bioinformatic analysis further reveals that this construct potently activates integrin α5-PI3K/AKT signaling pathway through mechanical and biophysical cues, and thereby repairing critical-sized bone defect. The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue, and offers a critical research model for in-depth studying the structure-function relationship of bone.

Introduction The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤ 3 and > 3 lesions, respectively. Results A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n=69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1–58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p=0.009; multivariate analysis: HR 0.363, p=0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p

Abstract Background Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. Methods We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. Results A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914–4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score. Conclusions The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC.

Abstract Background Periodontitis is closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg. Methods To explore the influence of Pg on cognitive function, neuropathology and immune balance in vivo, 5xFAD mice were treated with live Pg by oral gavage, three times a week for 1 month. The cells of peripheral blood, spleen and bone marrow from 5xFAD mice were treated with Pg to detect the proportional and functional alterations of mMDSCs in vitro. Next, exogenous mMDSCs were sorted from wild-type healthy mice and intravenously injected into 5xFAD mice that were infected with Pg. We used behavioral tests, flow cytometry and immunofluorescent staining to evaluate whether exogenous mMDSCs could ameliorate the cognitive function, immune homeostasis and reduce neuropathology exacerbated by Pg infection. Results Pg exacerbated cognitive impairment in 5xFAD mice, with the deposition of amyloid plaque and increased number of microglia in the hippocampus and cortex region. The proportion of mMDSCs decreased in Pg-treated mice. In addition, Pg reduced the proportion and the immunosuppressive function of mMDSCs in vitro. Supplement of exogenous mMDSCs improved the cognitive function, and enhanced the proportions of mMDSCs and IL-10+ T cells of 5xFAD mice infected with Pg. At the same time, supplement of exogenous mMDSCs increased the immunosuppressive function of endogenous mMDSCs while decreased the proportions of IL-6+ T cells and IFN-γ+ CD4+ T cells. In addition, the deposition of amyloid plaque decreased while the number of neurons increased in the hippocampus and cortex region after the supplement of exogenous mMDSCs. Furthermore, the number of microglia increased with an increase in the proportion of M2 phenotype. Conclusions Pg can reduce the proportion of mMDSCs, induce immune-overreaction, and exacerbate the neuroinflammation and cognitive impairment in 5xFAD mice. Supplement of exogenous mMDSCs can reduce the neuroinflammation, immune imbalance and cognitive impairment in 5xFAD mice infected with Pg. These findings indicate the mechanism of AD pathogenesis and Pg-mediated promotion of AD, and provide a potential therapeutic strategy for AD patients.

Abstract Guided bone regeneration (GBR) is widely used in treating oral bone defects to exclude the influence of non-osteogenic tissue on the bone healing process. The traditional method of GBR with a titanium mesh to treat large-area bone defects is limited by the deficiency of increased trauma and costs to patients. Herein, a bi-layered scaffold for GBR composed of a fiber barrier layer and a self-healing hydrogel repair layer is successfully fabricated. The barrier layer is a fibrous membrane material with specific porosity constructed by electrospinning, while the functional layer is a self-healing hydrogel material formed by multiple dynamic covalent bonds. The system can provide an osteogenic microenvironment by preventing the infiltration of connective tissue to bone defects, maintain the stability of the osteogenic space through the self-healing property, and regulate the release of bioactive substances in the dynamic physical condition, which is beneficial to osteoblast proliferation, differentiation, and bone regeneration. This study focused on exploring the effects of different crosslinkers and bonding methods on the comprehensive properties of hydrogels. and proved that the hybrid scaffold system has good biocompatibility, cell barrier function and can enhance bone regeneration activity. Thereby it could be a promising clinical strategy for bone regeneration.

Collecting emotional physiological signals is significant in building affective Human-Computer Interactions (HCI). However, how to evoke subjects’ emotions efficiently in EEG-related emotional experiments is still a challenge. In this work, we developed a novel experimental paradigm that allows odors dynamically participate in different stages of video-evoked emotions, to investigate the efficiency of olfactory-enhanced videos in inducing subjects’ emotions; According to the period that the odors participated in, the stimuli were divided into four patterns, i.e., the olfactory-enhanced video in early/later stimulus periods (OVEP/OVLP), and the traditional videos in early/later stimulus periods (TVEP/TVLP). The differential entropy (DE) feature and four classifiers were employed to test the efficiency of emotion recognition. The best average accuracies of the OVEP, OVLP, TVEP, and TVLP were 50.54%, 51.49%, 40.22%, and 57.55%, respectively. The experimental results indicated that the OVEP significantly outperformed the TVEP on classification performance, while there was no significant difference between the OVLP and TVLP. Besides, olfactory-enhanced videos achieved higher efficiency in evoking negative emotions than traditional videos. Moreover, we found that the neural patterns in response to emotions under different stimulus methods were stable, and for Fp1, FP2, and F7, there existed significant differences in whether adopt the odors.

Abstract Background A soluble form of cytotoxic‐T‐lymphocyte‐antigen‐4 (sCTLA‐4) is a prognostic biomarker for several cancers but remains unclear in HCC patients. The aim of study is to evaluate the predictive role of serum sCTLA‐4 levels for tumor recurrence of chronic hepatis C (CHC)‐HCC patients receiving radiofrequency ablation (RFA). Material and method A prospective study recruiting 88 CHC‐HCC patients was done between 2013 and 2019. Cox regression analysis was used to determine the predictors of early recurrence. All tests were two‐tailed, and the level of statistical significance was set as p 9 ng/ml) encountered shorter recurrence‐free survival (RFS) for LR (log‐rank p = 0.017) but paradoxically longer RFS for IHM (log‐rank p = 0.007) compared to those with low levels (≤9 ng/ml). By multivariate Cox regression analysis, sCTLA‐4 levels and antiviral therapy were independent prognostic factor of early recurrence both in LR and IHM. A combination of baseline sCTLA‐4 and AFP level could improve the predictability of early LR and IHM with specificity of 80.0% and 79.7% and positive predictive value of 63.3% and 67.3%, respectively. Conclusions sCTLA‐4 level is a good predictor for early HCC recurrence with higher levels indicating susceptibility to early LR, but protecting from early IHM.

Abstract Hepatocellular carcinoma (HCC) can be potentially discovered from abdominal computed tomography (CT) studies under varied clinical scenarios (e.g., fully dynamic contrast‐enhanced [DCE] studies, noncontrast [NC] plus venous phase [VP] abdominal studies, or NC‐only studies). Each scenario presents its own clinical challenges that could benefit from computer‐aided detection (CADe) tools. We investigate whether a single CADe model can be made flexible enough to handle different contrast protocols and whether this flexibility imparts performance gains. We developed a flexible three‐dimensional deep algorithm, called heterophase volumetric detection (HPVD), that can accept any combination of contrast‐phase inputs with adjustable sensitivity depending on the clinical purpose. We trained HPVD on 771 DCE CT scans to detect HCCs and evaluated it on 164 positives and 206 controls. We compared performance against six clinical readers, including two radiologists, two hepatopancreaticobiliary surgeons, and two hepatologists. The area under the curve of the localization receiver operating characteristic for NC‐only, NC plus VP, and full DCE CT yielded 0.71 (95% confidence interval [CI], 0.64–0.77), 0.81 (95% CI, 0.75–0.87), and 0.89 (95% CI, 0.84–0.93), respectively. At a high‐sensitivity operating point of 80% on DCE CT, HPVD achieved 97% specificity, which is comparable to measured physician performance. We also demonstrated performance improvements over more typical and less flexible nonheterophase detectors. Conclusion: A single deep‐learning algorithm can be effectively applied to diverse HCC detection clinical scenarios, indicating that HPVD could serve as a useful clinical aid for at‐risk and opportunistic HCC surveillance.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.

Candida albicans is an opportunistic pathogenic yeast that can survive in both normoxic and hypoxic environments. The involvement of C. albicans secretome on host biological processes has been demonstrated. However, the immunoregulatory function of C. albicans secretome released under hypoxic condition remains unclear. This study demonstrated the differences in cytokine responses and protein profiles between secretomes prepared under normoxic and hypoxic conditions. Furthermore, the immunoregulatory effects of heat shock protein SSA1(Ssa1), a protein candidate enriched in the hypoxic secretome, were investigated. Stimulation of mouse bone marrow-derived macrophages (BMMs) with Ssa1 resulted in the significant production of interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α as well as the significant expression of M2b macrophage markers (CD86, CD274 and tumor necrosis factor superfamily member 14), suggesting that C. albicans Ssa1 may promote macrophage polarization towards an M2b-like phenotype. Proteomic analysis of Ssa1-treated BMMs also revealed that Ssa1 reduced inflammation-related factors (IL-18-binding protein, IL-1 receptor antagonist protein, OX-2 membrane glycoprotein and cis-aconitate decarboxylase) and enhanced the proteins involved in anti-inflammatory response (CMRF35-like molecule 3 and macrophage colony-stimulating factor 1 receptor). Based on these results, we investigated the effect of Ssa1 on C. albicans infection and showed that Ssa1 inhibited the uptake of C. albicans by BMMs. Taken together, our results suggest that C. albicans alters its secretome, particularly by promoting the release of Ssa1, to modulate host immune response and survive under hypoxic conditions.

Abstract Current evidence has suggested that diabetes increases the risk of implanting failure, and therefore, appropriate surface modification of dental implants in patients with diabetes is crucial. TiO2 nanotube (TNT) has an osteogenic nanotopography, and its osteogenic properties can be further improved by loading appropriate drugs. Cinnamaldehyde (CIN) has been proven to have osteogenic, anti-inflammatory, and anti-bacterial effects. We fabricated a pH-responsive cinnamaldehyde-TiO2 nanotube coating (TNT-CIN) and hypothesized that this coating will exert osteogenic, anti-inflammatory, and anti-bacterial functions in a simulated diabetes condition. TNT-CIN was constructed by anodic oxidation, hydroxylation, silylation, and Schiff base reaction to bind CIN, and its surface characteristics were determined. Conditions of diabetes and diabetes with a concurrent infection were simulated using 22-mM glucose without and with 1-μg/mL lipopolysaccharide, respectively. The viability and osteogenic differentiation of bone marrow mesenchymal stem cells, polarization and secretion of macrophages, and resistance to Porphyromonas gingivalis and Streptococcus mutans were evaluated. CIN was bound to the TNT surface successfully and released better in low pH condition. TNT-CIN showed better osteogenic and anti-inflammatory effects and superior bacterial resistance than TNT in a simulated diabetes condition. These findings indicated that TNT-CIN is a promising, multifunctional surface coating for patients with diabetes needing dental implants. Graphical abstract

Staphylococcus aureus and Pseudomonas aeruginosa are well-known opportunistic pathogens that frequently coexist in chronic wounds and cystic fibrosis. The exoproducts of P. aeruginosa have been shown to affect the growth and pathogenicity of S. aureus, but the detailed mechanisms are not well understood. In this study, we investigated the effect of extracellular vesicles from P. aeruginosa (PaEVs) on the growth of S. aureus. We found that PaEVs inhibited the S. aureus growth independently of iron chelation and showed no bactericidal activity. This growth inhibitory effect was also observed with methicillin-resistant S. aureus but not with Acinetobacter baumannii, Enterococcus faecalis, S. Typhimurium, E. coli, Listeria monocytogenes, or Candida albicans, suggesting that the growth inhibitory effect of PaEVs is highly specific for S. aureus. To better understand the detailed mechanism, the difference in protein production of S. aureus between PaEV-treated and non-treated groups was further analyzed. The results revealed that lactate dehydrogenase 2 and formate acetyltransferase enzymes in the pyruvate fermentation pathway were significantly reduced after PaEV treatment. Likewise, the expression of ldh2 gene for lactate dehydrogenase 2 and pflB gene for formate acetyltransferase in S. aureus was reduced by PaEV treatment. In addition, this inhibitory effect of PaEVs was abolished by supplementation with pyruvate or oxygen. These results suggest that PaEVs inhibit the growth of S. aureus by suppressing the pyruvate fermentation pathway. This study reported a mechanism of PaEVs in inhibiting S. aureus growth which may be important for better management of S. aureus and P. aeruginosa co-infections.

Acinetobacter baumannii is a major causative agent of nosocomial infections and its outer membrane vesicles (AbOMVs) have been shown to be involved in pathogenicity by transporting virulence factors and transferring information for communication between pathogens and host cells. Despite the fact that the infected sites of A. baumannii such as lungs and skin soft tissues are hypoxic, most studies on AbOMV virulence have used AbOMVs prepared under aerobic conditions. The present study aims to elucidate the protein profile and pathogenic impact of AbOMVs released under hypoxic condition. AbOMVs were isolated from A. baumannii under normoxic and hypoxic conditions, and their protein profiles were compared. The different effects of both normoxic and hypoxic AbOMVs in cytokine response from mouse macrophages, cytotoxicity to the human lung epithelial cells, and bacterial invasion were then investigated. Our results showed that A. baumannii under hypoxia released larger amounts of OMVs with different protein profiles. Although the cytotoxic effect of AbOMVs from normoxia and hypoxia were comparable, AbOMVs from normoxia induced higher TNF-α production and invasion of Staphylococcus aureus and Pseudomonas aeruginosa than those from hypoxia. On the other hand, AbOMVs significantly enhanced A. baumannii invasion into lung epithelial cells in a dose-dependent manner. These results clearly demonstrate that AbOMVs released from normoxic and hypoxic have different impacts in pathogenesis. This finding provides new insight into the complex interactions between A. baumannii, coinfecting pathogens and host cells via OMVs, in particular the different pathogenic effects of AbOMVs under normoxic and hypoxic conditions.

The power industry is a basic industry related to the national economy and people’s livelihood and has important strategic value.It has obvious characteristics of technology and capital intensiveness.In recent years, there has been fruitful scientific and technological achievements which have won many national science and technology awards in this industry.Three typical areas were selected: the UHV transmission technology, the safety and operation technology of the large power grid and the new energy technologyto elaborate the strong technical vitality, the international influence, the talent cultivation ability and the industrial driving capabilities of the award-winning projects.It was fully verified the National Awards have a strong role in promoting the power industry and the technological innovation can effectively promote the collaborative innovation and development of power grid technology, and it is of great significance to support China to achieve “carbon peak and carbon neutrality” as soon as possible.

Abstract Maintenance strategies aim at reduction of the operation and maintenance cost of wind turbines. An opportunistic maintenance strategy offers cost advantages over the traditional preventive replacement maintenance strategy by considering cost dependency among maintenance activities. A new opportunistic maintenance strategy of wind turbines is proposed here. First, the proposed strategy includes two sets of reliability thresholds to handle subassemblies those are in operational and failed wind turbines. Using the reliability thresholds, ten maintenance modes and their service conditions are presented. Second, the Weibull distribution with an age reduction factor is introduced to describe reliability variation of subassemblies under imperfect maintenance. Third, the maintenance cost in each maintenance mode is expressed by a reliability variation‐based function that is dependent on the stage of maintenance activities. Fourth, due to the randomness of failures, the expected total maintenance cost is determined with Monte Carlo simulation. The proposed approach has been validated with the data provided by a wind farm located in Northern China.

Abstract Background Rhabdomyolysis is a serious and potentially life threatening condition that can be caused by drugs. We report a case of acute hepatitis B with rhabdomyolysis after treatment with rosuvastatin and entecavir. Case presentation A 72-year-old female was admitted to our hospital due to acute hepatitis B infection. She had taken atorvastatin for 3 months before being admitted to our hospital. After being administered entecavir (ETV) and rosuvastatin to replace atorvastatin, she suffered from muscle pain in both lower limbs and was diagnosed with rhabdomyolysis. After discontinuation of the two drugs, the patient's symptoms subsided and creatine kinase levels returned to normal. We hypothesize that the rhabdomyolysis was caused by the combination of rosuvastatin and ETV. Conclusions We suggest that patients who use rosuvastatin and ETV be made aware of the complication of rhabdomyolysis.

Background: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. Aims: This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. Methods: Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. Results: In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. Conclusions: MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.

This study aimed to examine (1) the psychometric properties of The Teachers' Sense of Efficacy Scale (TSES) in early childhood (EC) preservice (N = 202) and in-service (N = 182) teachers, and (2) the effect of teaching experience on efficacy beliefs. Findings indicated that EC teachers' efficacy beliefs were best represented by a bifactor model (i.e., one general and three specific factors); teachers generally perceived their capabilities in teaching at a more general level rather than specific to different classroom functions. Teaching experience had a significant effect on efficacy beliefs for preservice but not for in-service teachers. This study fills a gap in our understanding of EC teachers' sense of efficacy by providing empirical evidence on the structure of efficacy beliefs and the effect of teaching experience on efficacy beliefs in preservice and in-service EC teachers. In this study, a new efficacy factor named Responsive Teaching emerged, capturing an element of in-service EC teachers' perceptions of their capabilities that may be specific to the EC setting. Findings regarding the effects of experience on preservice EC teachers' sense of efficacy may provide guidance on targeted instruction to increase sense of efficacy.

Given the omnipresence and profoundness of the ongoing pandemic from the Coronavirus disease 2019, its potential spread can be minimized through social distancing. However, this practice causes increasing difficulties and undesirability of traditional transactions or interactions. Accordingly, various manufacturing firms around the world have become more committed not only to accelerating the development of digital technologies, but also to integrating them with existing processes. In this study, we address an important issue of how manufacturing firms can adapt to the ever-changing volatility and unpredictable global business environment, and achieve sustainable growth by developing a strong supply chain management capability. Two specific interrelated research questions are considered: (1) How do supply chain management capabilities contribute to firm environmental performance; and (2) What are the sources of such capabilities? In so doing, we integrate various forms of digital innovation into a supply chain management capability logic to explore their antecedents and consequences. By using survey data from 272 manufacturing firms in China, we examine the relationship between three key forms of digital innovation (i.e., product, platform, and service) and firm environmental performance. Results show that digital product, platform, and service innovations all have positive contributions to supply chain management capability. In turn, supply chain management capabilities have a partial mediating effect between digital product innovation and firm environmental performance, but a full mediating effect between digital platform and service innovations and firm environmental performance.

Abstract In traditional opportunistic group replacement maintenance (OGRM) strategy for wind turbines, the reliability thresholds of different subassemblies are set the same and its two‐step optimization for maintenance cost is diseconomy. In this paper, an improved OGRM strategy for wind turbines is proposed. A uniform formulation on maintenance cost concerning different maintenance activities is presented. On the basis of this, an integrated objective function minimizing the maintenance cost is established, and the reliability thresholds of each subassembly of wind turbines are individually severed as the optimization variables of the objective function. The coordinate rotation method is utilized for solving this optimization problem. A maintenance case based on the proposed strategy from a wind farm in North China is implemented, which verifies its superior performance than the traditional opportunistic group maintenance strategy.

Background & aims: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) patients. Variceal bleeding is a life-threatening complication and may alter the initial treatment plan. This study was aimed to elucidate the risk factors for variceal bleeding in HCC patients receiving TACE treatment. Methods: From 2005 to 2016, a total of 1233 treatment-naive HCC patients receiving first time TACE treatment in Chang Gung Memorial Hospital, Linkou medical center were recruited. Pre-TACE status including baseline characteristics, prior history of ascites, and parameters for liver function evaluation were analyzed. All the variables were compared between patients with and without variceal bleeding. Results: Among the 1233 patients, the median age was 63.7 (range 25.8–91.5) years old, and 73.5% were male. Variceal bleeding events were documented in 19 patients (1.5%) within 3 months post TACE treatment. Patients with younger age, cirrhosis, pre-treatment ascites and advanced fibrosis status (higher MELD score, CTP score, ALBI grade, FIB-4 and APRI score) were more likely to encounter post-treatment variceal bleeding. Multivariate Cox regression analysis revealed existence of ascites (adjusted HR: 4.859 (1.947–12.124), p = 0.001), and higher FIB-4 score (adjusted HR: 4.481 (1.796–11.179), p = 0.001) were the independent predictive factors for variceal bleeding. Patients with post-TACE variceal bleeding are more likely to encounter tumor progression (42.1% vs. 20.3%, p = 0.039) and mortality owing to GI bleeding (15.8% vs. 3%, p = 0.032). Conclusion: The incidence of post-TACE variceal bleeding was 1.5%. Patients with post-TACE variceal bleeding have poorer TACE treatment response. The pre-treatment ascites and FIB-4 score are the independent predictors for post-TACE variceal bleeding. Keywords: Ascites, Gastrointestinal bleeding, Mortality, Portal hypertension, Treatment response

Accurate remaining useful life prognosis of bearings in wind turbines can effectively help to schedule maintenance strategy and reduce operational costs at wind farms. Unscented particle filter is good at state tracking in nonlinear problem. A robust model-based approach based on improved unscented particle filter is presented to deal with bearing life prognosis in wind turbines, which involves: (1) The mean of sigma points after unscented Kalman transform is regarded as the particles in particle filter to guarantee the particles aggregation; (2) Several past measurements are utilized to estimate the likelihood function of current step; (3) Uniform distribution is adopted for resampling particles to make them diversity. The presented remaining useful life prognosis approach depends more on the measurement, rather than the initial parameters of degradation model, which makes it practicable for the on-site wind turbines. Three life-cycle bearings from wind turbine high-speed shafts demonstrate the effectiveness of the proposed approach.

Background The impact of prolonged post-ablation fever (PAF) defined as persistent fever > 24 h after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) had not been described before. This study aims to investigate the impact of prolonged PAF on early tumor recurrence in HCC patients after RFA. Methods From 2013 to 2015, a total of 135 patients with HCC meeting Milan criteria and all the tumors having confirmed complete ablation after RFA were enrolled. Study endpoint was any HCC recurrence within 1 year after ablation. Cox regression analysis was applied for multivariate analysis to determine the independent predictors of 1-year tumor recurrence. Results Post-ablation fever occurred in 42 (31.1%) patients after RFA, while prolonged PAF was found in 22 (16.3%) patients. Fifty-eight (42.8%) patients occurred any tumor recurrence within 1 year after complete ablation. Patients with prolonged PAF had a significantly higher rate of HCC recurrence within 1 year (72.7% vs. 37.1%, p = 0.002) and had a significantly shorter time-to-recurrence interval (19.6 vs. 40.5 months, Log rank test, p = 0.002) than those who had no prolonged PAF. Multivariate analysis by Cox regression showed the previous HCC recurrence history (aHR: 1.792, p = 0.0284), baseline AFP > 20 ng/ml (aHR: 1.868, p = 0.0211) and prolonged PAF (aHR: 2.092, p = 0.0138) were associated with early recurrence. Conclusions Prolonged PAF may associate with early HCC recurrence after complete ablation by RFA. Patients with prolonged PAF need to be more clinical attentions.

Acupuncture is widely used in the treatment of cerebral hemorrhage, and it improves outcomes in experimental animal models and patients. However, the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear. In this study, a model of intracerebral hemorrhage was produced by injecting 50 μL autologous blood into the caudate nucleus in Wistar rats. Acupuncture at Baihui (DU20) and Qubin (GB7) acupoints was performed at a depth of 1.0 inch, 12 hours after blood injection, once every 24 hours. The needle was rotated at 200 r/min for 5 minutes, For each 30-minute session, needling at 200 r/min was performed for three sessions, each lasting 5 minutes. For the positive control group, at 6 hours, and 1, 2, 3 and 7 days after induction of hemorrhage, the rats were intraperitoneally injected with 1 mL aniracetam (0.75 mg/mL), three times a day. The Bederson behavioral test was used to assess palsy in the contralateral limbs. Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia. Immunohistochemistry was performed to count the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Acupuncture effectively reduced hemorrhage and brain edema, elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia, and increased the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Together, these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors. The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center (approval No. 2017061001) on June 10, 2017.

BackgroundPeriodontal pathogen and gut microbiota are closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, can induce cognitive impairment. The gut has a connection and communication with the brain, which is an important aspect of the gut–brain axis (GBA). In the present study, we investigate whether Pg induces cognitive impairment through disturbing the GBA.MethodsIn this study, Pg was orally administered to mice, three times a week for 1 month. The effects of Pg administration on the gut and brain were evaluated through behaviors, gut microbiota, immune cells, glymphatic pathway clearance, and neuroinflammation.ResultsPg induced cognitive impairment and dysbiosis of gut microbiota. The α-diversity parameters did not show significant change after Pg administration. The β-diversity demonstrated that the gut microbiota compositions were different between the Pg-administered and control groups. At the species level, the Pg group displayed a lower abundance of Parabacteroides gordonii and Ruminococcus callidus than the control group, but a higher abundance of Mucispirillum schaedleri. The proportions of lymphocytes in the periphery and myeloid cells infiltrating the brain were increased in Pg-treated animals. In addition, the solute clearance efficiency of the glymphatic system decreased. Neurons in the hippocampus and cortex regions were reduced in mice treated with Pg. Microglia, astrocytes, and apoptotic cells were increased. Furthermore, amyloid plaque appeared in the hippocampus and cortex regions in Pg-treated mice.ConclusionsThese findings indicate that Pg may play an important role in gut dysbiosis, neuroinflammation, and glymphatic system impairment, which may in turn lead to cognitive impairment.

To study the effect of scalp acupuncture (SA) on the mitophagy signaling pathway in the caudate nucleus of Sprague-Dawley rats following intracerebral hemorrhage (ICH). An ICH model was established by injecting autologous arterial blood into the caudate nucleus in 200 male Sprague-Dawley rats, which were divided into five groups: sham, ICH, 3-methyladenine group (3-MA, 30 mg/kg), SA, and SA+3-MA. Animals were analyzed at 6 and 24 h as well as at 3 and 7 days. Composite neurological scale score was significantly higher in the SA group than in the ICH group. Transmission electron microscopy showed less structural damage and more autophagic vacuoles within brain in the SA group than in the ICH group. SA group showed higher levels of Beclin1, Parkin, PINK1, NIX protein, and a lower level of Caspase-9 in brain tissue. These animals consequently showed less neural cell apoptosis. Compared with the SA group, however, the neural function score and levels of mitophagy protein in the SA+3-MA group were decreased, neural cell apoptosis was increased with more severe structural damage, which suggested that 3-MA may antagonize the protective effect of SA on brain in rats with ICH. SA may mitigate the neurologic impairment after ICH by enhancing mitophagy and reducing apoptosis.

The key to evaluating the health status of cable-stayed bridges lies in the accuracy of cable force measurement. When measuring the cable force using the conventional frequency method, the clearance between the bracing cable and the protective tube is typically disregarded. Moreover, due to their large size, existing vibration sensors are difficult to install into protective tubes for steel strand-type bracing cables to measure the cable force. To address the above difficulties, a type of thin rod vibration sensor only 5 mm in diameter was designed based on the high sensitivity of Fiber Bragg grating (FBG), and high-throughput data processing software for engineering calculation (EC) was self-developed. Then, the recognition principle of the thin rod vibration sensor was theoretically analyzed and a step-by-step tension test was carried out. The results demonstrated that the relative error of the cable force measured by the thin rod vibration sensor within 12.865 Hz was less than 5% and the sensitivity reached 28.7 pm/Hz, indicating its high measurement precision. Upon subsequent application of the thin rod vibration sensor to a monitoring test in the field, the relative error of the fundamental frequency between artificial and natural excitations was less than 4%. In addition, the error relative to both the theoretical frequency and the third-party sampling frequency was less than 5%, further verifying the accuracy and applicability for monitoring the cable force of bridges under natural excitation. Compared with the traditional cantilever FBG sensor, the improved sensor with supporting data processing software has the advantages of small cross-section, high reliability, and good sensitivity. The research results can provide a reference for the subsequent accurate measurement of cable force and the development of a supporting sensor data processing system.

DC power distribution systems will play an important role in the future urban power distribution system, while the charging and discharging requirements of electric vehicles have a great impact on the voltage stability of the DC power distribution systems. A robust control method based on H∞ loop shaping method is proposed to suppress the effect of uncertain integration on voltage stability of DC distribution system. The results of frequency domain analysis and time domain simulation show that the proposed robust controller can effectively suppress the DC bus voltage oscillation caused by the uncertain integration of electric vehicle, and the robustness is strong.

Background: Secondary prevention of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC) who achieve sustained virologic response (SVR) with interferon-based therapy has been proved effective. However, tertiary prevention with PegIFN/RBV therapy of HCC recurrence seems limited effect in CHC-HCC patients post curative therapies. This study aims to investigate the timing and impact of PegIFN/RBV treatment on prevention of HCC recurrence in patients after RFA treatment. Methods: From 2013 to 2016, a total of 137 CHC-HCC patients from a 508 patient based cohort receiving complete RFA treatment in Chang Gung Memorial Hospital, Linkou Medical Center were retrospectively recruited. Pre-RFA patient demographics were analyzed by cox regression analysis for prediction on tumor recurrence. Statistics analysis was performed with SPSS V.20 (IBM, USA). Results: The mean age of the 137 patients were 69.6 year-old and 71.5% of patients were cirrhotic. After propensity score matching, one hundred and two patients were enrolled into the analysis. Fifty-one patients (50%) received PegIFN/RBV therapy and twenty-seven patients (52.9%) achieved SVR. Patients who could achieve SVR had lower tumor recurrence rate than non-SVR and untreated groups (29.6% vs. 66.7% vs. 49.0%, P = 0.030). The effect is more prominent in those achieve SVR prior to compared with after RFA despite not reach statistically significant (26.1% vs. 50.0%, P = 0.334). Conclusion: Timely treatment with SVR achievement has the lowest tumor recurrence rate in CHC-HCC patients. Secondary prevention might be even more important than tertiary prevention in CHC patients, especially regarding prevention of post RFA HCC recurrence. Keywords: Radiofrequency ablation, Haptocellular carcinoma, Peginterferon and ribavirin, Prognosis

Tamias Sibiricus is the only member of the genus Tamias, a significant and vigorous seed distributor and vital food for their predators. No information is known about the strict diet, gut microbiota structure, and metabolism profile of chipmunks and how they diversify seasonally. The above factors, as well as flexibility toward seasonal shifts, are critical in defining its growth rates, health, survivorship, and population stability. This study explored the diet, gut microbiota composition, and chipmunk metabolism. Additionally, the influence of different seasons was also investigated by using next-generation sequencing. Results revealed that seasons strongly affected a diet: streptophyte accounted for 37% in spring, which was lower than in summer (34.3%) and autumn (31.4%). Further, Ascomycota was observed at 43.8% in spring, which reduced to 36.6% in summer and the lowest (31.3%) in autumn. Whereas, nematodes showed maximum abundance from spring (15.8%) to summer (20.6%) and autumn (24.1%). These results signify the insectivorous nature of the chipmunk in summer and autumn. While herbivorous and fungivorous nature in spring. The DNA analysis revealed that chipmunk mainly feeds on fungi, including Aspergillus and Penicillium genus. Similar to diet composition, the microbiome also exhibited highly significant dissimilarity (p < 0.001, R = 0.235) between spring/autumn and spring/summer seasons. Proteobacteria (35.45%), Firmicutes (26.7%), and Bacteroidetes (23.59%) were shown to be the better discriminators as they contributed the most to causing differences between seasons. Moreover, PICRUSt showed that the assimilation of nutrients were also varied seasonally. The abundance of carbohydrates, lipids, nucleotides, xenobiotics, energy, terpenoids, and polyketides metabolism was higher in spring than in other seasons. Our study illustrates that seasonal reconstruction in the chipmunk diet has a significant role in shaping temporal variations in gut microbial community structure and metabolism profile.

The technology of fault diagnosis is helpful to improve the reliability of wind turbines, and further reduce the operation and maintenance cost at wind farms. However, in reality, wind turbines are not allowed to operate with faults, so few fault samples could be obtained. With a small amount of training data, traditional fault diagnosis models that need huge samples under a deep learning framework are difficult to maintain with high accuracy and effectiveness. Few-shot learning can effectively solve the problem of overfitting caused by fewer fault samples in model training. In view of model-agnostic meta-learning (MAML), this paper proposes a model for few-shot fault diagnosis of the wind turbines drivetrain, which is named model-agnostic meta-baseline (MAMB). The training data is input to the base classification model for pre-training, then, some data is randomly selected from the training set to form multiple meta-learning tasks that are utilized to train the MAML to finally fine-tune the later layers of the model at a smaller learning rate. The proposed model was analyzed by the small samples of the bearing data from Case Western Reserve University (CWRU) data, the generator bearings, and gearboxes vibration data in wind turbines under randomly changing operating conditions. The results verified that the proposed method was superior in one-shot, five-shot, and ten-shot tasks of wind turbines.

Despite tremendous attention is given to the construction of biomimetic cementum for regeneration of tooth cementum, the lack of recapitulating the composition and hierarchical structure of cementum often leads to the poor performance of constructed materials. How to highly mimic the sophisticated composition and hierarchy of cementum remains a longstanding challenge in constructing the biomimetic cementum. Inspired by cementum formation process, a novel construction approach via a combination of bioskiving and fluorine-containing biomineralization is developed in this study. The alternative collagen lamellae (ACL) that can highly mimic the rotated plywood structure of cementum collagen matrix is fabricated via bioskiving. Followed by biomineralization in the amorphous calcium phosphate (ACP) solution with different concentration of fluorine, a series of biomimetic cementum is constructed. Screened by physicochemical characterization, the biomimetic cementum with the composition and hierarchical structure highly similar to human cementum is selected. Through in vitro biological assay, this biomimetic cementum is proven to significantly promote the adhesion, proliferation, and cementogenic differentiation of periodontal ligament cells (PDLCs). Furthermore, in vivo study demonstrates that biomimetic cementum could induce cementogenesis. This biomimetic cementum constructed via combinatory application of bioskiving and fluorine-containing biomineralization stands as a promising candidate for achieving cementum regeneration.

Grafting bone substitute is paramount to prevent the alveolar ridge resorption after tooth extraction and facilitate the subsequent implant treatment. An ideal bone substitute should acquire the excellent osteogenic property, more importantly, possess the suitable remodeling rate in balance with bone formation and desirable clinical manageability. However, none of bone substitute is simultaneously characterized by these features, and currently, the limited remodeling property leads to the excessive waiting time before implantation. Enlightened by woven bone, the transitional tissue that is able to induce osteogenesis during bone healing could be easily remodeled within a short period and depend on the favorable injectability of hydrogel, an injectable woven bone-like hydrogel (IWBLH) was constructed in this study to address the above problems. To mimic the component and hierarchical structure of woven bone, amorphous calcium phosphate (ACP) and mineralized collagen fibril were synthesized and compounded with alginate to form IWBLHs with various ratio. Screened by physiochemical characterization and in vitro biological assays, an optimal IWBLH was selected and further explored in rat model of tooth extraction. Compared with the most widely used bone substitute, we showed that IWBLH could be easily handled to fully fill the tooth socket, perform a comparable function to prevent the alveolar bone resorption, and completely remodeled within 4 weeks. This IWBLH stands as a promising candidate for alveolar ridge preservation (ARP) in future.

Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is seldom discussed. Therefore, this study aimed to investigate the application of ALBI grade and dynamic change of ALBI grade (delta ALBI grade) after first TACE for prognosis prediction in HCC patients with chronic hepatitis C infection. Method: From January 2005 to December 2015, newly diagnosed naive chronic hepatitis C-hepatocellular carcinoma (CHC-HCC) patients who were treated with TACE as the initial treatment at the Chang Gung Memorial Hospital, Linkou Medical Center, were retrospectively recruited. The pre-treatment host factors, tumor status and noninvasive markers were collected. The Cox regression model was used to identify independent predictors of overall survival and tumor recurrence. Results: Among 613 treatment-naive CHC-HCC patients, 430 patients died after repeated TACE during a median follow-up of 26.9 months. Complete remission after repeated TACE occurred in 46.2% patients, and 208 patients (33.9%) had tumor recurrence, with a median recurrence-free interval of 8.5 months. In Cox regression analysis, ALBI grade II/III (aHR: 1.088, p = 0.035) and increased delta ALBI grade (aHR: 1.456, p = 0.029) were independent predictive factors for tumor recurrence. Furthermore, ALBI grade II/III (aHR: 1.451, p = 0.005) and increased delta ALBI grade during treatment (aHR: 1.436, p = 0.006) were predictive factors for mortality, while achieving complete response after repeated TACE (aHR: 0.373, p < 0.001) and anti-viral therapy (aHR: 0.580, p = 0.002) were protective factors for mortality. Conclusion: Both ALBI and delta ALBI grade are independent parameters to predict survival and tumor recurrence of CHC-HCC patients receiving TACE treatment.

Abstract Mitochondria autophagy, termed as mitophagy, is a mechanism of specific autophagic elimination of mitochondria. Mitophagy controls the quality and the number of mitochondria, eliminating dysfunctional or excessive mitochondria that can generate reactive oxygen species (ROS) and cause cell death. Mitochondria are centrally implicated in neuron and tissue injury after stroke, due to the function of supplying adenosine triphosphate (ATP) to the tissue, regulating oxidative metabolism during the pathologic process, and contribution to apoptotic cell death after stroke. As a catabolic mechanism, mitophagy links numbers of a complex network of mitochondria, and affects mitochondrial dynamic process, fusion and fission, reducing mitochondrial production of ROS, mediated by the mitochondrial permeability transition pore (MPTP). The precise nature of mitophagy’s involvement in stroke, and its underlying molecular mechanisms, have yet to be fully clarified. This review aims to provide a comprehensive overview of the integration of mitochondria with mitophagy, also to introduce and discuss recent advances in the understanding of the potential role, and possible signaling pathway, of mitophagy in the pathological processes of both hemorrhagic and ischemic stroke. The author also provides evidence to explain the dual role of mitophagy in stroke.

Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. Methods: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2–4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. Results: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage. However, there is no research showing the relationship between this treatment and cell apoptosis. Rat models of intracerebral hemorrhage were established by injecting 60 μL of autologous blood into the right side of the caudate-putamen. Six hours later, the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint. The needle was alternately rotated (180 ± 10 turns/min) manually along clockwise and counter-clockwise directions. Stimulation lasted for 7 days, and was performed three times each for 6 minutes with 6-minute intervals between stimulations. Rats intraperitoneally receiving Sonic hedgehog pathway activator, purmorphamine (1 mg/kg per day), served as positive controls. Motor and sensory function were assessed using the Ludmila Belayev test. Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining. Apoptosis was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Expression of smoothened (Smo) and glioma-associated homolog 1 (Gli1) was determined by western blot assay. Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function, reduced the apoptotic cell percentage in the perihemorrhagic penumbra, and up-regulated Smo and Gli1 expression. We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage, possibly by activating the Sonic hedgehog pathway.

Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autologous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1β mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our results showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and interkeukin-1β. Moreover, this effect was similar to piceatannol. These findings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.