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In this paper, a data-driven modeling method for precast concrete (PC) balcony components was proposed to solve the problems of low informatization and the difficult modeling of components at the design stage. Through the analysis of the characteristics of PC balcony components and the combination of modular design methods, the paper designed a data structure for the components and developed a data-driven modeling tool for PC balcony components that can realize the input of structural design data, automatically generating component models. First, this paper introduced the data-driven modeling concept and the modeling process. Second, the PC balcony components in common prefabricated residential projects were analyzed to identify their characteristics. By using a modular design approach, these components were divided and a module dataset was created based on the split modules. Consequently, a data structure for the prefabricated balcony component model was established, wherein both conventional parameters and adaptive parameters between modules were interrelated. Finally, the function of data-driven modeling was achieved by developing a modular design tool on the Revit platform using the C# programming language. The application conducted on a prefabricated building project demonstrated that the software tool and modeling method in this paper effectively improve the level of informatization and modeling efficiency of PC balcony components. The modular design approach was satisfied with the standardization and diversification requirements of balcony components, thereby offering insights for modeling other complex components. [ABSTRACT FROM AUTHOR]

The design and production of prefabricated buildings pose challenges in achieving standardization, limiting their extensive adoption. In order to address issues of prefabricated components, such as the low reusability of design knowledge, limited standardization, and design disconnection, this paper adopted the prefabricated cantilevered structure components as the research object. It employs knowledge-based engineering (KBE) theory and secondary split modularization approach in conjunction with Revit secondary development technology to establish a modular design system. The system formalizes complex design knowledge into concise user interfaces and a logically clear programming language, ensuring the design system's ease of use and accessibility. To validate the authenticity and applicability of the modular design system developed in this paper, a comparison is made between the traditional modeling tool and modular modeling tool. Through empirical analysis, the result indicates that the new tool proposed in this paper can enhance the efficiency of design professionals by 72.92%. Among these, the tool meets the modeling and design requirements of 96.1% of the prefabricated components in the project, making it highly suitable for the modeling and design process of the vast majority of prefabricated components. Therefore, this design approach, which integrates KBE and three-dimensional geometric technology, makes the modular design of prefabricated cantilevered structural components feasible, providing a reference for future research in the design of other prefabricated components. [ABSTRACT FROM AUTHOR]

Ultra‐high ductile concrete (UHDC) is known for ultra‐high tensile ductility, and ultra‐high performance concrete (UHPC) has ultra‐high compressive strength. Reinforced UHDC–UHPC panels that are made of UHDC and UHPC (i.e., hybrid panels) are expected to have excellent blast‐resistance capacity. However, only limited research is devoted to study the dynamic performance of the panels under explosion. To further investigate the dynamic performance of such kind of composite structural system, numerical simulations are carried out through LS‐DYNA. The developed material models are used for describing the mechanical properties of UHDC, UHPC and steel bars at high strain rate. Based on the corresponding field blast test results, the feasibility and accuracy of the adopted finite element models are validated. Furthermore, parameter analysis is applied for investigating the effects of scale distance, reinforcement ratio and concrete type on the dynamic performance. It is concluded that the maximum deflection of reinforced UHDC–UHPC panels reduces with increasing scale distance and reinforcement ratio. Reinforced UHDC–UHPC panels possess excellent blast‐resistance capacity in comparison with reinforced concrete panels. [ABSTRACT FROM AUTHOR]

Oriented object detection is a practical and challenging task in remote sensing image interpretation. Nowadays, oriented detectors mostly use horizontal boxes as intermedium to derive oriented boxes from them. However, the horizontal boxes are inclined to get small Intersection-over-Unions (IoUs) with ground truths, which may have some undesirable effects, such as introducing redundant noise, mismatching with ground truths, and detracting from the robustness of detectors. In this article, we propose a novel anchor-free oriented proposal generator (AOPG) that abandons horizontal box-related operations from the network architecture. AOPG first produces coarse oriented boxes by a coarse location module (CLM) in an anchor-free manner and then refines them into high-quality oriented proposals. After AOPG, we apply a Fast Region-based Convolutional Neural Network (R-CNN) head to produce the final detection results. Furthermore, the shortage of large-scale datasets is also a hindrance to the development of oriented object detection. To alleviate the data insufficiency, we release a new dataset on the basis of our DIOR dataset and name it DIOR-R. Massive experiments demonstrate the effectiveness of AOPG. Particularly, without bells and whistles, we achieve the accuracy of 64.41%, 75.24%, and 96.22% mAP on the DIOR-R, DOTA, and HRSC2016 datasets, respectively. Code and models are available at https://github.com/jbwang1997/AOPG. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) are hyperactive in many cancers and have served as cancer therapeutic targets for decades. Palbociclib (Palb) is the first approved CDK4/6 inhibitor to treat hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Acquired drug resistance is one obstacle of Palb be utilized in other cancer. CDK2 compensation of CDK4/6 loss is one of the causes that cancer cells are resistant to Palb. Hence, targeting multiple CDKs could be a novel strategy to prevent the drug resistance of cancer cells and expand the application of Palb in other cancer. In this study, we initially indicated Polyphyllin I (PPI) significantly inhibits non-small lung cancer cell (NSCLC) proliferation, promotes cell apoptosis in vitro and in vivo. Mechanistically, PPI can inhibit Rb through the p21/CDK2/Rb signaling pathway in NSCLC. A combination of PPI and Palb exerts a significant synergistic anti-cancer ability on NSCLC. Of note, PPI can reverse Palb drug resistance. Herein, we first time demonstrated PPI can disturb CDK2 function through upregulation of p21. The PPI effect on CDK2 provides a choice for a chemotherapeutic strategy for the elimination of NSCLC. Our study highlighted the clinical significance of simultaneously blocking of CDK2 and CDK4/6 for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is one of the most common chronic diseases in the world. Epidemiological evidence and clinical trials have shown that ω-3 fatty acids have a variety of promoting effects in reducing the risk of ASCVD, but different conclusions of large randomized controlled trials make their clinical use in the prevention and treatment of ASCVD controversial. The present review focuses on the pharmacological mechanism, clinical trials and evidence value of clinical applications of ω-3 fatty acids in order to provide theoretical and practical evidence for the clinical application strategy, and follow-up research and development of ω-3 fatty acids as anti-ASCVD drugs. [ABSTRACT FROM AUTHOR]

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions. [ABSTRACT FROM AUTHOR]

Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study. [ABSTRACT FROM AUTHOR]

The xCo3O4/Ce0.85Co0.15-3xO2-δ catalyst was prepared by a sol-gel method for selective catalytic oxidation of NO. The experimental results showed that the highest catalytic activity reached 60.2% at 300 °C. In addition, the Raman spectra and XPS results confirmed that the Ce-Co catalyst contained surface free Co3O4 species and Co ions in the Ce0.85Co0.15-3xO2-δ solid solution. Surface free Co3O4 species could be removed by hydrochloric acid, leading to decrease of the catalyst activity. For the xCo3O4/Ce0.85Co0.15-3xO2-δ catalyst, the surface free Co3O4 species and the Ce0.85Co0.15-3xO2-δ solid solution enhanced catalytic performance, and the former provided the adsorption sites of NO and the latter promoted the activation of oxygen. This research studied the synergetic effects of Co3O4 species and Ce0.85Co0.15-3xO2-δ solid solution on the process of NO oxidation. For the xCo3O4/Ce0.85Co0.15-3xO2-δ catalyst, the enhanced catalytic performance was due to the synergy between the surface Co3O4 species and the Ce0.85Co0.15-3xO2-δ solid solution, as the former provided the sites for NO chemisorption and the latter promoted the activation of oxygen. [ABSTRACT FROM AUTHOR]

Uterine natural killer (uNK) cells have been hypothesized to serve a role in controlling trophoblast invasion and proliferation. The aim of the present study was to identify the distribution and number of uNK cells in normal pregnancy (NP), partial mole (PM), complete mole (CM) and invasive mole (IM). uNK cells were detected using dolichos biflorus agglutinin lectin immunohistochemistry in decidual and villous tissues from early NP (n=15), late NP (n=15), PM (n=22), CM (n=20) and IM (n=10). A scaled eye piece was used for cell counting to obtain semi-quantitative results. It was revealed that uNK cells were mainly located in the uterine deciduas of early NP. As pregnancy progressed, the number of decidual uNK cells significantly decreased. Decidual uNK cells of PM, CM and IM were located near blood vessel endothelial cells. No significant differences were detected with respect to the numbers of decidual uNK between early NP and PM. However, the number of decidual uNK cells was significantly reduced in CM and IM compared with early NP. The populations of decidual uNK cells were not significantly different between CM and IM. No uNK cells were detected in the villi of PM, CM or IM. The decrease of decidual uNK cells in late NP, CP and IM, compared with early NP, suggested that uNK cells served an important role in controlling trophoblast invasion and proliferation. [ABSTRACT FROM AUTHOR]

Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Uterine natural killer (uNK) cells are short-lived, terminally differentiated and the most abundant lymphocytes in the uterus which play a crucial role in the spiral arteriole modification and establishment of successful pregnancy. Dysregulation of uNK cells has been linked to gestational implications such as recurrent pregnancy loss, preeclampsia and fetal growth retardation. There is evidence showing that progesterone and estrogen can regulate the recruitment, proliferation, differentiation and function of uNK cells via direct action on intracellular nuclear receptors or through intermediary cells in the uterus during early pregnancy. As the deepening of related research in this field, the role of conceptus in such regulation has received extensive attention, it utilizes endocrine signaling (hCG), juxtacrine signaling (HLA-C, HLA-E, HLA-G) and paracrine signaling (cytokines) to facilitate the activities of uNK cells. In addition, under the influence of ovarian hormones, conceptus can increase expression of PIBF and HLA-G molecules to reduce cytotoxicity of uNK cells and promote angiogenesis. In this review, we aim to concentrate on the novel findings of ovarian hormones in the regulation of uNK cells, emphasize the regulatory role of conceptus on uNK cells and highlight the proposed issues for future research in the field. [ABSTRACT FROM AUTHOR]

Background: The combination of methimazole and propranolol is considered an effective treatment regimen for hyperthyroidism in clinical practice; however, detrimental effects on the heart rate, bone metabolism and thyroid hormone levels have been reported. Therefore, the present study aimed to systematically review the efficacy and safety differences in patients with hyperthyroidism and the effects of treatment on heart rate, bone metabolism, cortisol, and adrenocorticotropic hormone levels using case-control studies., Methods: Clinical case-control trials of methimazole combined with propranolol for the treatment of hyperthyroidism were selected from Chinese and English databases, and data were collected from the establishment of the database until August 2024. Two independent researchers evaluated the quality of the literature using the Newcastle-Ottawa Scale (NOS). Meta-analysis of each effect index was performed using RevMan software (version 5.3), and the quality of the results was evaluated using the GRADE profiler system letter description method., Results: Sixteen clinical case-control trials were included in this study. Of these, 2 trials exhibited NOS scores of 7, 6 trials exhibited NOS scores of 6, and 8 trials exhibited NOS scores of 5. These accounted for 12.5% of the high-quality literatures, and included 772 patients treated with methimazole combined with propranolol (observation group) and 771 patients treated with methimazole alone (control group). The results of the meta-analysis demonstrated that methimazole combined with propranolol improved the cure rate, the total effective rate, and heart rate, compared with the control group (P < .05). In addition, calcification, bone glutamate protein, free triiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, cortisol, and adrenocorticotropic hormone were significantly different between the 2 groups (P < .05). There were no significant differences in leukemia, headache, dizziness, skin pruritus, bone pain, arthralgia, or in improving parathyroid hormone or reducing gastrointestinal reactions between the 2 groups., Conclusion: The present study demonstrated that methimazole combined with propranolol may significantly improve the heart rate, bone metabolism and associated hormone levels in patients with hyperthyroidism, without significantly increasing the risk of adverse reactions. However, due to the impact of primary literature type, quality or research methods high-quality, multicenter, rigorously designed clinical trials are required for further verification., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (Mecp2) gene. Here, we found that inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) kinase ameliorated progression of motor dysfunction after onset and prolonged the survival of Mecp2-null mice. Microglia were activated early in myeloid Mecp2-deficient mice, which was inhibited upon inactivation of RIPK1 kinase. RIPK1 inhibition in Mecp2-deficient microglia reduced oxidative stress, cytokines production and induction of SLC7A11, SLC38A1, and GLS, which mediate the release of glutamate. Mecp2-deficient microglia release high levels of glutamate to impair glutamate-mediated excitatory neurotransmission and promote increased levels of GluA1 and GluA2/3 proteins in vivo, which was reduced upon RIPK1 inhibition. Thus, activation of RIPK1 kinase in Mecp2-deficient microglia may be involved both in the onset and progression of RTT., Competing Interests: Competing interests statement:The authors declare no competing interest.

Object detection is a fundamental yet challenging task in computer vision. Despite the great strides made over recent years, modern detectors may still produce unsatisfactory performance due to certain factors, such as non-universal object features and single regression manner. In this paper, we draw on the idea of mutual-assistance (MA) learning and accordingly propose a robust one-stage detector, referred as MADet, to address these weaknesses. First, the spirit of MA is manifested in the head design of the detector. Decoupled classification and regression features are reintegrated to provide shared offsets, avoiding inconsistency between feature-prediction pairs induced by zero or erroneous offsets. Second, the spirit of MA is captured in the optimization paradigm of the detector. Both anchor-based and anchor-free regression fashions are utilized jointly to boost the capability to retrieve objects with various characteristics, especially for large aspect ratios, occlusion from similar-sized objects, etc. Furthermore, we meticulously devise a quality assessment mechanism to facilitate adaptive sample selection and loss term reweighting. Extensive experiments on standard benchmarks verify the effectiveness of our approach. On MS-COCO, MADet achieves 42.5% AP with vanilla ResNet50 backbone, dramatically surpassing multiple strong baselines and setting a new state of the art.

With the rise of deep convolutional neural networks, object detection has achieved prominent advances in past years. However, such prosperity could not camouflage the unsatisfactory situation of Small Object Detection (SOD), one of the notoriously challenging tasks in computer vision, owing to the poor visual appearance and noisy representation caused by the intrinsic structure of small targets. In addition, large-scale dataset for benchmarking small object detection methods remains a bottleneck. In this paper, we first conduct a thorough review of small object detection. Then, to catalyze the development of SOD, we construct two large-scale Small Object Detection dAtasets (SODA), SODA-D and SODA-A, which focus on the Driving and Aerial scenarios respectively. SODA-D includes 24828 high-quality traffic images and 278433 instances of nine categories. For SODA-A, we harvest 2513 high resolution aerial images and annotate 872069 instances over nine classes. The proposed datasets, as we know, are the first-ever attempt to large-scale benchmarks with a vast collection of exhaustively annotated instances tailored for multi-category SOD. Finally, we evaluate the performance of mainstream methods on SODA. We expect the released benchmarks could facilitate the development of SOD and spawn more breakthroughs in this field.

Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of MDD, while it can effectively prevent the recurrence of MDD during the maintenance period. Currently, the results of systematic reviews on vortioxetine are insufficient since several efficacy measures, such as the 24-Items Hamilton Rating Scale for Depression (HADRS-24) total score and other safety factors have not been evaluated. Therefore, the present study aimed to evaluate the efficacy and safety of different doses of vortioxetine on the treatment of adult patients with MDD via assessing more efficacy and safety indicators. The clinical, double-blind, parallel and randomized controlled trials (RCTs) on the effect of vortioxetine on MDD were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and clinical trial registration websites from database inception to November 2022. A total of two investigators independently screened the included references and independently evaluated their quality. The meta-analysis was performed using Revman 5.0 software. The present systematic review was registered in PROSPERO (registration no. CRD42018106343). In the present study 11 RCTs were included, with a total of 4,908 adult patients with MDD. More specifically, 1,158 patients were included in the 5-mg vortioxetine group, 736 in the 10-mg group, 298 in the 15-mg group, 864 in the 20-mg group and 1,852 in the placebo group. All 11 studies were randomized, double-blinded and parallel control trials, and all publications were evaluated as high quality. The meta-analysis results showed that patients in the 5-, 10- and 20-mg vortioxetine groups exhibited significantly higher Montgomery-Asberg Depression Rating Scale (MADRS) response (≥50%) and remission (≤10%) rates compared with the placebo group (P<0.05). The pooled analysis also revealed a statistically significant change in the total score of HADRS-24, MADRS, Sheehan Disability Scale (SDS), Clinical Global Impression Scale-Improvement (CGI-I) and HADRS-24 response rate in the 10- and 20-mg vortioxetine groups compared with the placebo group (P<0.05). However, no statistically significant changes in the total score of HADRS-24, MADRS, SDS, CGI-I and HADRS-24 response rate were obtained in the 5-mg group compared with the placebo group (P>0.05). Furthermore, the most common adverse events were nausea, hyperhidrosis, insomnia and vomiting, the incidence of which was increased with higher doses of vortioxetine. Overall, the results suggested that vortioxetine administration at doses of 5-20 mg was significantly effective and safe compared with placebo in the treatment of MDD. However, 5 mg vortioxetine displayed no difference in the HADRS-24, MADRS, SDS and CGI-I total scores, and HADRS-24 response rate. Furthermore, patient treatment with increasing vortioxetine doses was associated with good tolerance and high safety. Nevertheless, more multi-center, high-quality and long-term RCTs are still needed to support the aforementioned findings., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gao et al.)

Adenosine monophosphate-activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser 415 to suppress energy stress-induced cell death. Inhibiting pS415-RIPK1 by Ampk deficiency or RIPK1 S415A mutation promoted RIPK1 activation. Furthermore, genetic inactivation of RIPK1 protected against ischemic injury in myeloid Ampkα1 -deficient mice. Our studies reveal that AMPK phosphorylation of RIPK1 represents a crucial metabolic checkpoint, which dictates cell fate response to metabolic stress, and highlight a previously unappreciated role for the AMPK-RIPK1 axis in integrating metabolism, cell death, and inflammation.

The ubiquitin-proteasome system (UPS) and autophagy are two major intracellular degradative mechanisms that mediate the turnover of complementary repertoires of intracellular proteomes. Simultaneously activating both UPS and autophagy might provide a powerful strategy for the clearance of misfolded proteins. However, it is not clear whether UPS and autophagy can be controlled by a common regulatory mechanism. K48 deubiquitination by USP14 is known to inhibit UPS. Here we show that USP14 regulates autophagy by negatively controlling K63 ubiquitination of Beclin 1. Furthermore, we show that activation of USP14 by Akt-mediated phosphorylation provides a mechanism for Akt to negatively regulate autophagy by promoting K63 deubiquitination. Our study suggests that Akt-regulated USP14 activity modulates both proteasomal degradation and autophagy through controlling K48 and K63 ubiquitination, respectively. Therefore, regulation of USP14 provides a mechanism for Akt to control both proteasomal and autophagic degradation. We propose that inhibition of USP14 may provide a strategy to promote both UPS and autophagy for developing novel therapeutics targeting neurodegenerative diseases., (© 2016 Xu et al.; Published by Cold Spring Harbor Laboratory Press.)

Avian tembusu virus (TMUV), which was first identified in eastern China, is an emerging virus causing serious economic losses in the Chinese poultry industry. Here, we report the complete genome sequence of goose tembusu virus strain JS804, isolated from Jiangnan white geese with severe neurological signs. The genome of JS804 is 10,990 nucleotides (nt) in length and contains a single open reading frame encoding a putative polyprotein of 3,425 amino acids. Research of the whole sequence of tembusu virus will help us to understand further the molecular and evolutionary characteristics and pathogenesis of this virus.