Coxsackievirus A6 2C protein antagonizes IFN-ß production through MDA5 and RIG-I depletion.

IMPORTANCE: Coxsackievirus A6 (CV-A6) is a major emerging pathogen associated with atypical hand, foot, and mouth disease and can cause serious complications such as encephalitis, acute flaccid paralysis, and neurorespiratory syndrome. Therefore, revealing the associated pathogenic mechanisms could benefit the control of CV-A6 infections. In this study, we demonstrate that the nonstructural 2CCV-A6 suppresses IFN-ß production, which supports CV-A6 infection. This is achieved by depleting RNA sensors such as melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I (RIG-I) through the lysosomal pathway. Such a function is shared by 2CEV-A71 and 2CCV-B3 but not 2CCV-A16, suggesting the latter might have an alternative way to promote viral replication. This study broadens our understanding of enterovirus 2C protein regulation of the RIG-I-like receptor signaling pathway and reveals a novel mechanism by which CV-A6 and other enteroviruses evade the host innate immune response. These findings on 2C may provide new therapeutic targets for the development of effective inhibitors against CV-A6 and other enterovirus infections.

Erbium: YAG laser treatment efficacy and association with histologic features for giant congenital melanocytic nevi management.

BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

Microscopic Understanding of Interfacial Performance and Antifoaming Mechanism of REP Type Block Polyether Nonionic Surfactants.

In many practical applications involving surfactants, achieving defoaming without affecting interfacial activity is a challenge. In this study, the antifoaming performance of REP-type block polymer nonionic surfactant C12EOmPOn was determined, and molecular dynamics simulation method was employed to investigate the molecular behaviors of surfactants at a gas/water interface, the detailed arrangement information of the different structural segments of the surfactant molecules and the inter-/intra-interactions between all the structural motifs in the interfacial layer were analyzed systematically, by which the antifoaming mechanisms of the surfactants were revealed. The results show that the EO and PO groups of REP-type polyether molecules are located in the aqueous phase near the interface, and the hydrophobic tails distribute separately, lying almost flat on the gas/water interface. The interaction between the same groups of EOs and POs is significantly stronger than with water. REP block polyethers with high polymerization degrees of EO and PO are more inclined to overlap into dense layers, resulting in the formation of aggregates resembling "oil lenses" spreading on the gas/water interface, which exerts a stronger antifoaming effect. This study provides a smart approach to obtaining efficient antifoaming performance at room temperature without adding other antifoam ingredients.

Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.

Nef Suppresses LINE-1 Retrotransposition through Two Distinct Mechanisms.

Long interspersed element type 1 (LINE-1) is the only known type of retroelement that can replicate autonomously, and its retrotransposition activity can trigger interferon (IFN) production. IFN production suppresses the infectivity of exogenous viruses, such as human immunodeficiency virus (HIV). As a counteraction, HIV has been reported to use multiple proteins and mechanisms to suppress LINE-1 replication. However, the mechanisms of HIV-mediated LINE-1 regulation are not fully understood. In this study, we discovered that Nef protein, which is expressed by HIV and is important for HIV pathogenesis, inhibits LINE-1 retrotransposition. Two distinct mechanisms have been uncovered for Nef-induced LINE-1 suppression. Without direct interaction with LINE-1 DNA, Nef potently inhibits the promoter activity of the LINE-1 5'-untranslated region (5'-UTR) and reduces the expression levels of LINE-1 RNA and proteins. Alternatively, although Nef does not bind to the LINE-1 open reading frame 1 protein (ORF1p) or LINE-1 RNA, it significantly compromises the ORF1p-LINE-1 RNA interaction, which is essential for LINE-1 retrotransposition. Both mechanisms can be suppressed by the G2A mutation, which abolishes myristoylation of Nef, suggesting that membrane attachment is essential for Nef to suppress LINE-1. Consequently, through LINE-1 inhibition, Nef downregulates IFN production in host cells. Therefore, our data revealed that Nef is a potent LINE-1 suppressor and an effective innate immune regulator, which not only provides new information on the intricate interaction between HIV, LINE-1, and IFN signaling systems but also strengthens the importance of Nef in HIV infection and highlights the potential of designing novel Nef-targeting anti-HIV drugs. IMPORTANCE Human immunodeficiency viruses are pathogens of AIDS that were first discovered almost 40 years ago and continue to threaten human lives to date. While currently used anti-HIV drugs are sufficient to suppress viral loads in HIV-infected patients, both drug-resistant HIV strains and adverse side effects triggered by the long-term use of these drugs highlight the need to develop novel anti-HIV drugs targeting different viral proteins and/or different steps in viral replication. To achieve this, more information is required regarding HIV pathogenesis and especially its impact on cellular activities in host cells. In this study, we discovered that the Nef protein expressed by HIV potently inhibits LINE-1 retrotransposition. During our attempt to determine the mechanism of Nef-mediated LINE-1 suppression, two additional functions of Nef were uncovered. Nef effectively repressed the promoter activity of LINE-1 5'-UTR and destabilized the interaction between ORF1p and LINE-1 RNA. Consequently, Nef not only compromises LINE-1 replication but also reduces LINE-1-triggered IFN production. The reduction in IFN production, in theory, promotes HIV infectivity. Together with its previously known functions, these findings indicate that Nef is a potential target for the development of novel anti-HIV drugs. Notably, the G2 residue, which has been reported to be essential for most Nef functions, was found to be critical in the regulation of innate immune activation by Nef, suggesting that compromising myristoylation or membrane attachment of Nef may be a good strategy for the inhibition of HIV infection.

BST2 Suppresses LINE-1 Retrotransposition by Reducing the Promoter Activity of LINE-1 5' UTR.

Endogenous retrotransposons are considered the "molecular fossils" of ancient retroviral insertions. Several studies have indicated that host factors restrict both retroviruses and retrotransposons through different mechanisms. Type 1 long interspersed elements (LINE-1 or L1) are the only active retroelements that can replicate autonomously in the human genome. A recent study reported that LINE-1 retrotransposition is potently suppressed by BST2, a host restriction factor that prevents viral release mainly by physically tethering enveloped virions (such as HIV) to the surface of producer cells. However, no endoplasmic membrane structure has been associated with LINE-1 replication, suggesting that BST2 may utilize a distinct mechanism to suppress LINE-1. In this study, we showed that BST2 is a potent LINE-1 suppressor. Further investigations suggested that BST2 reduces the promoter activity of LINE-1 5' untranslated region (UTR) and lowers the levels of LINE-1 RNA, proteins, and events during LINE-1 retrotransposition. Surprisingly, although BST2 apparently uses different mechanisms against HIV and LINE-1, two membrane-associated domains that are essential for BST2-mediated HIV tethering also proved important for BST2-induced inhibition of LINE-1 5' UTR. Additionally, by suppressing LINE-1, BST2 prevented LINE-1-induced genomic DNA damage and innate immune activation. Taken together, our data uncovered the mechanism of BST2-mediated LINE-1 suppression and revealed new roles of BST2 as a promoter regulator, genome stabilizer, and innate immune suppressor. IMPORTANCE BST2 is a potent antiviral protein that suppresses the release of several enveloped viruses, mainly by tethering the envelope of newly synthesized virions and restraining them on the surface of producer cells. In mammalian cells, there are numerous DNA elements replicating through reverse transcription, among which LINE-1 is the only retroelement that can replicate autonomously. Although LINE-1 retrotransposition does not involve the participation of a membrane structure, BST2 has been reported as an efficient LINE-1 suppressor, suggesting a different mechanism for BST2-mediated LINE-1 inhibition and a new function for BST2 itself. We found that BST2 specifically represses the promoter activity of LINE-1 5' UTR, resulting in decreased levels of LINE-1 transcription, translation, and subsequent retrotransposition. Additionally, by suppressing LINE-1 activity, BST2 maintains genome stability and regulates innate immune activation. These findings expand our understanding of BST2 and its biological significance.

Three-core photonic crystal fiber for the in-line measurement of full-polarization states by multi-core polarization interference theory.

In this Letter, we demonstrate and experimentally verify the application of three-core photonic crystal fiber (3C-PCF) for the in-line detection of fully polarized states. We prove the response of 3C-PCF to full-polarization states under multi-core polarization interference through experiments. The sensitivity at 1472 nm is 0.0273 nm/rad, and the linear response is better than 98.9% (the optimal operating wavelength can be designed in the range of 1470 to 1570 nm). With the advantages of an all-fiber integrated system, robustness, and wide wavelength coverage, our design holds great promise for facilitating fiber-optic-integrated polarization meters for optical fiber communication and biomedical diagnostic applications.

Strategies adopted by Salmonella to survive in host: a review.

Salmonella, a Gram-negative bacterium that infects humans and animals, causes diseases ranging from gastroenteritis to severe systemic infections. Here, we discuss various strategies used by Salmonella against host cell defenses. Epithelial cell invasion largely depends on a Salmonella pathogenicity island (SPI)-1-encoded type 3 secretion system, a molecular syringe for injecting effector proteins directly into host cells. The internalization of Salmonella into macrophages is primarily driven by phagocytosis. After entering the host cell cytoplasm, Salmonella releases many effectors to achieve intracellular survival and replication using several secretion systems, primarily an SPI-2-encoded type 3 secretion system. Salmonella-containing vacuoles protect Salmonella from contacting bactericidal substances in epithelial cells and macrophages. Salmonella modulates the immunity, metabolism, cell cycle, and viability of host cells to expand its survival in the host, and the intracellular environment of Salmonella-infected cells promotes its virulence. This review provides insights into how Salmonella subverts host cell defenses for survival.

How to synergize ecological restoration to co-benefit the beneficial contributions of nature to people on the Qinghai-Tibet Plateau?

Understanding the magnitude and spatial distribution of ecological restoration requires a precise assessment of the beneficial contributions of nature to people. However, where the restoration areas should be located and whether the natural contribution of a compensation area can satisfy people's needs in the context of ecological degradation remain unclear. To address these issues, we selected the Qinghai-Tibet Plateau as the study areas, utilizing the offset portfolio analyzer and locator model to identify the compensation sites that offset the losses of ecosystem services and biodiversity resulting from ecological degradation. These compensation sites were developed through two offset types: restoration and protection. Then, based on the offset sites, we assessed nature's contribution to people (NCP) under the current status and future scenarios in terms of various aspects, including the habitat (NCP1), climate change (NCP4), and water quantity and flow regulation (NCP6). This study found that the area impacted by agricultural development was 7.15 × 105 ha, and the required compensation area was 5.5 × 106 ha under the current status. The ratio of the impacted area to the required area was approximately 7.0 in the future scenarios. The average habitat qualities were 0.14 and 0.30, while the mean NCP1 values were 2.69 and 0.51 in the protection and restoration offset sites, respectively. Moreover, based on the offset sites, the high-value contributions in NCP4 accounted for 18.64%-22.69% and 38.87%-46.17% of the total offset sites in terms of the restoration and protection offset types, respectively. Additionally, the estimated high-value contributions in NCP6 accounted for 58.35%-59.02% and 84.40%-95.86% of the total offset sites in the restoration and protection offset types, respectively. Our findings highlighted the significance of ecological restoration in showcasing the role of NCPs. These results could aid conservation managers in developing more targeted ecological strategies to enhance human well-being.

Identification of potentially functional circRNAs and prediction of circRNA-miRNA-mRNA regulatory network in periodontitis: Bridging the gap between bioinformatics and clinical needs.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue-dependent and disease-dependent. This study aimed to identify novel periodontitis-associated circRNAs and predict relevant circRNA-periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic. MATERIAL AND METHODS: High-throughput sequencing and RT-qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA-disease association prediction, and circRNA-miRNA-mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver-operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs. RESULTS: High-throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT-qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40-.69, p < .05, moderate). A circRNA-miRNA-mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321-0.8667, p < .05). CONCLUSION: CircRNA-disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560-23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.

Surface Charge Regulated Asymmetric Ion Transport in Nanoconfined Space.

The asymmetric ion transport in the nanoconfined space, similar to that of natural ion channels, has attracted broad interest in sensor, energy conversion, and other related fields. Among these systems, the surface charge plays an important role in regulating ion transport behaviors. Herein, this surface charge-regulated asymmetric ion transport behavior is systematically explored in the nanoconfined space and the influence on the performance of nanofluidic energy conversion system. The ion transport behaviors in the nanoconfined space are classified into pure diffusion, electrical double layer, and the polarization controlled state. The asymmetric solution environment or surface charge distribution induces asymmetric ion transport behavior which is largely controlled by the low concentration side. The ion-selectivity and the energy conversion performance can be effectively enhanced by improving the local apparent surface charge (more active sites and higher charge strength) or introducing a selective layer with dense surface charge on the low concentration side. These material design concepts for asymmetric ion transport are further supported by both simulation and experiment. The results provide a significant comprehension for ion behaviors in nanoconfined space and the development of high-performance energy storage and conversion systems.

Evaluating the effectiveness of measures to control the novel coronavirus disease 2019 in Jilin Province, China.

BACKGROUND: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of measures to control the disease in Jilin Province, China. METHODS: The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible-Exposed-Infectious-Asymptomatic-Recovered/Removed (SEIAR) model was developed to fit the data, and the effective reproduction number (Reff) was calculated at different stages in the province. Finally, the effectiveness of the measures was assessed. RESULTS: A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit the reported data well (R2 = 0.593, P < 0.001). The Reff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would have reached a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would have been 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus's spread. CONCLUSIONS: COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proven effective; increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.

Associations of dietary and drinking water habits with number of natural teeth: a longitudinal study in the Chinese elderly population.

BACKGROUND: The relationship between dietary and drinking water habits and oral health are still unclear. We aimed at evaluating the association of dietary and drinking water habits with number of teeth in the elderly adults. METHODS: We conducted a longitudinal study based on the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2018. The data of dietary and drinking water habits at baseline were collected using a questionnaire. The number of teeth at baseline and follow-up was collected for each subject. We used the linear mixed-effect model to analyze the associations of dietary habits and drinking water sources with tooth number. RESULTS: Among 19,896 participants at baseline, the mean age of the participants was 83.87 years, with the average number of natural teeth of 9.37, 8.26, 8.38, 8.68, 4.05, 1.92, 1.12, 2.20 for the first to eighth waves of survey. Compared with subjects drinking tap water, 1.036 (95 % CI: -1.206, -0.865), 0.880 (95 % CI: -1.122, -0.637) and 1.331 (95 % CI: -1.715, -0.947) fewer natural teeth were reported for those drinking well, surface water and spring at baseline survey. Compared with participants with rice intake as the staple food, those with wheat intake (ß = -0.684; 95 % CI: -0.865, -0.503) tended to have fewer natural teeth. Compared with participants with fresh fruit intake almost every day, those with quite often intake of fresh fruit tended to have fewer teeth with a significant dose-response trend (Ptrend <0.001). Similar decreased trend for number of teeth was also indicated for increased frequency of vegetable intake (Ptrend <0.001). Fewer number of teeth was found for subjects with less frequency of meat and fish intakes. CONCLUSIONS: The study suggested that drinking well, surface water, and spring, intakes of wheat as staple food, as well as less frequency of fresh fruit, vegetable, meat and fish intakes were associated with significantly fewer number of teeth in the Chinese elderly population.

The hospital management practices in Chinese county hospitals and its association with quality of care, efficiency and finance.

BACKGROUND: County hospitals as the backbone of the China's healthcare system are providing services for over 70% of the total population. However, the hospital management practice (HMP) and its links with quality of care, efficiency and finance in these hospitals are unknown. METHODS: We did two cross-sectional surveys of HMP in 2013 and 2015 among 101 county hospitals across rural China. Three managing roles (hospital director, director of medical affairs office and director of cardiology) and a cardiologist were invited to the surveys. A novel HMP rating scale, with 100 as full score, was used to measure the HMP in 17 indicators under four dimensions (target, operation, performance, and talent management) for each hospital. We analyzed the association of HMP score with variables on quality of care, efficiency and finance using linear mixed models with and without adjustment for potential confounders. FINDINGS: A total of 95 hospitals participated in at least one survey and were included in the analysis. The overall mean HMP score varied dramatically across the hospitals and 84% of them scored less than 60. The dimension mean HMP score was 38.6 (target), 56.4 (operation), 53.2 (performance) and 55.7 (talent), respectively. The pattern of indicator mean HMP score, however, was almost identical between hospitals with high and low overall HMP score, showing the same 'strength' (staff satisfaction, staff performance appraisal, 'hard wares', patient-centered services, etc.) and 'weakness' (target balance, target setting, continuous quality improvement, penalties on staff with dissatisfied performance, etc.). The associations of overall mean HMP score with quality of care and efficiency variables and cost per hospitalization was not statistically significant. The statistical significance in the association with hospital annual total income disappeared after adjusting for region, teaching status, number of competitors, number of staff and number of beds in use. CONCLUSION: The HMP in Chinese county hospitals scores low in general and was not significantly associated with hospital care quality, efficiency and finance. The current healthcare reform in China should address the micro level issues in hospital management practices.

HuR in the Medial Prefrontal Cortex is Critical for Stress-Induced Synaptic Dysfunction and Depressive-Like Symptoms in Mice.

Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuRflox/flox;Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.

[Enlightenment on Carrying out Reporting Responsibility of Manufactures in China from Reviewing Medical Device Reporting Practice in US].

OBJECTIVE: By introducing the Medical Device Reporting (MDR) system and related inspection practice of the US, this paper puts forward some suggestions on implementing reporting responsibility of manufactures in China. METHODS: The MDR system and the related inspection system in the US were systematically analyzed. RESULTS: The US had established a sound system for discovering and reporting MDR, and a mechanism for inspecting the implementing of manufactures, forming an effective post-market surveillance system. CONCLUSIONS: By learning from the experience of the US, we can carry out the post-market surveillance of medical devices adverse events in China from the aspects of implementing the existing system, strengthening the reporting ability and perfecting the inspection mechanism.

Dual Model Medical Invoices Recognition.

Hospitals need to invest a lot of manpower to manually input the contents of medical invoices (nearly 300,000,000 medical invoices a year) into the medical system. In order to help the hospital save money and stabilize work efficiency, this paper designed a system to complete the complicated work using a Gaussian blur and smoothing-convolutional neural network combined with a recurrent neural network (GBS-CR) method. Gaussian blur and smoothing (GBS) is a novel preprocessing method that can fix the breakpoint font in medical invoices. The combination of convolutional neural network (CNN) and recurrent neural network (RNN) was used to raise the recognition rate of the breakpoint font in medical invoices. RNN was designed to be the semantic revision module. In the aspect of image preprocessing, Gaussian blur and smoothing were used to fix the breakpoint font. In the period of making the self-built dataset, a certain proportion of the breakpoint font (the font of breakpoint is 3, the original font is 7) was added, in this paper, so as to optimize the Alexnet-Adam-CNN (AA-CNN) model, which is more suitable for the recognition of the breakpoint font than the traditional CNN model. In terms of the identification methods, we not only adopted the optimized AA-CNN for identification, but also combined RNN to carry out the semantic revisions of the identified results of CNN, meanwhile further improving the recognition rate of the medical invoices. The experimental results show that compared with the state-of-art invoice recognition method, the method presented in this paper has an average increase of 10 to 15 percentage points in recognition rate.

Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant ß-catenin.

Hepatocellular cancer (HCC) remains a significant therapeutic challenge due to its poorly understood molecular basis. In the current study, we investigated two independent cohorts of 249 and 194 HCC cases for any combinatorial molecular aberrations. Specifically we assessed for simultaneous HMET expression or hMet activation and catenin ß1 gene (CTNNB1) mutations to address any concomitant Met and Wnt signaling. To investigate cooperation in tumorigenesis, we coexpressed hMet and ß-catenin point mutants (S33Y or S45Y) in hepatocytes using sleeping beauty transposon/transposase and hydrodynamic tail vein injection and characterized tumors for growth, signaling, gene signatures, and similarity to human HCC. Missense mutations in exon 3 of CTNNB1 were identified in subsets of HCC patients. Irrespective of amino acid affected, all exon 3 mutations induced similar changes in gene expression. Concomitant HMET overexpression or hMet activation and CTNNB1 mutations were evident in 9%-12.5% of HCCs. Coexpression of hMet and mutant-ß-catenin led to notable HCC in mice. Tumors showed active Wnt and hMet signaling with evidence of glutamine synthetase and cyclin D1 positivity and mitogen-activated protein kinase/extracellular signal-regulated kinase, AKT/Ras/mammalian target of rapamycin activation. Introduction of dominant-negative T-cell factor 4 prevented tumorigenesis. The gene expression of mouse tumors in hMet-mutant ß-catenin showed high correlation, with subsets of human HCC displaying concomitant hMet activation signature and CTNNB1 mutations. CONCLUSION: We have identified cooperation of hMet and ß-catenin activation in a subset of HCC patients and modeled this human disease in mice with a significant transcriptomic intersection; this model will provide novel insight into the biology of this tumor and allow us to evaluate novel therapies as a step toward precision medicine. (Hepatology 2016;64:1587-1605).