Photochemical Degradation of the New Nicotine Pesticide Acetamiprid in Water.

Acetamiprid is a novel nicotinic pesticide widely used in modern agriculture because of its low toxicity and specific biological target properties. The objective of this study was to understand the photolysis pattern of acetamiprid in the water column and elucidate its degradation products and mechanism. It was observed that acetamiprid exhibited different photolysis rates under different light source conditions in pure water, with ultraviolet > fluorescence > sunlight; furthermore, its photolysis half-life ranged from 17.3 to 28.6 h. In addition, alkaline conditions (pH 9.0) accelerated its photolysis rate, which increased with pH. Using gas chromatography-mass spectrometry, five direct photolysis products generated during the exposure of acetamiprid to pure water were successfully separated and identified. The molecular structure of acetamiprid was further analyzed using density functional theory, and the active photodegradation sites of acetamiprid were predicted. The mechanism of the photolytic transformation of acetamiprid in water was mainly related to hydroxyl substitution and oxidation. Based on these findings, a comprehensive transformation pathway for acetamiprid was proposed.

Genome-Wide Identification and Expression Profiling of Potato (Solanum tuberosum L.) Universal Stress Proteins Reveal Essential Roles in Mechanical Damage and Deoxynivalenol Stress.

Universal stress proteins (USPs) play an important regulatory role in responses to abiotic stress. Most of the research related to USPs so far has been conducted on plant models such as Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa L.), and cotton (Gossypium hirsutum L.). The potato (Solanum tuberosum L.) is one of the four major food crops in the world. The potato is susceptible to mechanical damage and infection by pathogenic fungi during transport and storage. Deoxynivalenol (DON) released by Fusarium can seriously degrade the quality of potatoes. As a result, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. Based on their genetic structure, the physical and chemical properties of their proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Solanum lycopersicum, Arabidopsis, Oryza sativa L., and Nicotiana attenuata) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that there are differences in the expression patterns of members of each subgroup under different abiotic stresses. A Weighted Gene Coexpression Network Analysis (WGCNA) of the central gene showed that the differential coexpression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide a basis for further research on the functional analysis of StUSPs in the response of potatoes to adversity stress.

Low LdMYB12 expression contributes to petal spot deficiency in Lilium davidii var. unicolor.

Petal spots are widespread in plants, they are important for attracting pollinators and as economic traits in crop breeding. However, the genetic and developmental control of petal spots has seldom been investigated. To further clarify the development of petal spots formation, we performed comparative transcriptome analysis of Lilium davidii var. unicolor and Lilium davidii petals at the full-bloom stage. In comparison with the parental species L. davidii, petals of the lily variety L. davidii var. unicolor do not have the distinct anthocyanin spots. We show that among 7846 differentially expressed genes detected, LdMYB12 was identified as a candidate gene contributing to spot formation in lily petals. The expression level of LdMYB12 in the petals of L. davidii was higher than that in L. davidii var. unicolor petals. Moreover, overexpression of LdMYB12 led to the appearance of spots on the petals of L. davidii var. unicolor, accompanied by increased expression of anthocyanin synthesis-related genes. Taken together, these results indicate that abnormal expression of LdMYB12 contributes to petal spot deficiency in L. davidii var. unicolor.

Exploration of Chick Embryo and Chorioallantoic Membrane on Imaging Navigated Platforms for Anticancer Pharmaceutical Evaluations.

Conforming to the current replace-reduce-refine 3Rs' guidelines in animal experiments, a series of explorative efforts have been made to set up operable biomedical imaging-guided platforms for qualitative and quantitative evaluations on pharmacological effects of tumor vascular-disrupting agents (VDAs), based on the chick embryos (CEs) with its chorioallantoic membrane (CAM), in this overview. The techniques and platforms have been hierarchically elaborated, from macroscopic to microscopic and from overall to specific aspects. A protocol of LED lamplight associated with a new deep-learning algorithm was consolidated to screen out weak CEs by using the CAM vasculature imaging. 3D magnetic resonance imaging (MRI) and laser speckle contrast imaging (LSCI) to monitor the evolution of CE and vascular changes in CAM are introduced. A LSCI-CAM platform for studying the effects of VDAs on normal and cancerous vasculature of CAM and possible molecular mechanisms has been demonstrated. Finally, practical challenges and future perspectives are highlighted. The aim of this article is to help peers in biomedical research to familiarize with the CAM platform and to optimize imaging protocols for the evaluation of vasoactive pharmaceuticals, especially anticancer vascular targeted therapy.

Porous Core-membrane Microstructured Nanomaterial Composed of Deep Eutectic Solvents and MOF-808 for CO2 Capture.

A series of porous core-membrane microstructured nanomaterials, constructed of a deep eutectic solvent (DES) membrane and porous MOF-808 core via liquid surface tensions and electrostatic interactions, are introduced for carbon dioxide capture with the sorption mechanism coupling diffusion, physisorption, and chemisorption. MOF-808 as the porous core considerably improves the diffusion interactions for DES membranes, hence significantly enhancing the sorption performance of DESs. Although the DES consisted by monoethanolamine and tetrapropylammonium chloride (MEA-TPAC-7) has the highest sorption capacity among all DESs, it is only 4.39 mmol g-1 at 2.4 bar and further attenuates by fastidious diffusion interactions when increasing viscosity or dose. The sorption capacities of DES@MOF-120 are 5.18 mmol g-1 at 3.0 bar and 4.78 mmol g-1 at 2.4 bar without apparent sorption hysteresis in pressure swing sorption, which are substantially improved contrasted to MEA-TPAC-7. The sorption isotherms are reconstructed via Sips models considering surface heterogeneity with regression correlation coefficients over 0.9454 to forecast maximum sorption capacity over 6.33 mmol g-1 .

Probabilistic real-time natural gas jet fire consequence modeling of offshore platforms by hybrid deep learning approach.

Natural gas jet fire induced by igniting blowouts has the potential to cause critical structure damage and great casualties of offshore platforms. Real-time natural gas jet fire plume prediction is essential to support the emergency planning to mitigate subsequent damage consequence and ocean pollution. Deep learning based on a large amount of Computational fluid dynamics (CFD) simulations has recently been applied to real-time fire modeling. However, existing approaches based on point-estimation theory are 'over-confident' when prediction deficiency exists, which reduce robustness and accuracy for emergency planning support. This study proposes probabilistic deep learning approach for real-time natural gas jet fire consequence modeling by integrating variational Bayesian inference with deep learning. Numerical model of natural gas jet fire from offshore platform is built and the natural gas jet fire scenarios are simulated to construct the benchmark dataset. Sensitivity analysis of pre-defined parameters such as MC (Monte Carlo) sampling number m and dropout probability p is conducted to determine the trade-off between model's accuracy and efficiency. The results demonstrated our model exhibits competitive accuracy with R2 = 0.965 and real-time capacity with an inference time of 12 ms. In addition, the predicted spatial uncertainty corresponding to spatial jet fire flame plume provides more comprehensive and reliable support for the following mitigation decision-makings compared to the state-of-the-art point-estimation based deep learning model. This study provides a robust alternative for constructing a digital twin of fire and explosion associated emergency management on offshore platforms.

Debilitation of Galleria mellonella hemocytes using CytCo a cytolytic-like protein derived from the entomopathogen Conidiobolus obscurus.

Cytolytic (Cyt)-like genes are present in both pathogenic bacteria and fungi. Bacterial Cyt proteins can destroy insect midgut epithelial cells after ingestion by hosts and some of them have been developed as biopesticides; however, few studies have investigated their functions in fungal pathogens. This study investigated the effects of a Cyt-like protein (CytCo) derived from Conidiobolus obscurus (Entomophthoromycotina) on the hemocytes of the greater wax moth Galleria mellonella larvae. The results showed a significant decline in hemocyte viability after treatment with CytCo in vivo or in vitro. The hemocyte density in the hemolymph was reduced by 65.2% and 50.2% after 12 h in vivo and 6 h in vitro treatments, respectively. Apoptosis/necrosis tests using fluorescence microscopy demonstrated that CytCo-treated hemocytes displayed apoptosis, and many of them also showed necrosis after 6 h in vitro treatment. Based on transcriptome analysis, several genes involved in the programmed cell death signaling pathway were upregulated in the CytCo-treated hemocytes. Meanwhile, the differentially expressed genes related to energy production, signal transduction, transcription regulation, and melanization were upregulated, demonstrating activated immune responses; those putatively related to hemocyte adhesion were downregulated, possibly in response to the reduction of hemocytes in hemolymph. In conclusion, CytCo as a virulence factor, could irreversibly incapacitate host hemocytes, playing an important role in debilitating insect immunity. This novel insecticidal protein holds a potential to develop biopesticide for controlling agroforestry pests.

Targeting Receptor-Interacting Protein Kinase 1 by Novel Benzothiazole Derivatives: Treatment of Acute Lung Injury through the Necroptosis Pathway.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are serious and devastating pulmonary manifestations of acute systemic inflammation with high morbidity and mortality worldwide. Currently, there are no specific effective treatments for ALI/ARDS. RIPK1, which contributes to necroptosis and inflammation, is confirmed to be a promising strategy for the treatment of ALI. Herein, 23 benzothiazole derivatives were designed to specifically target RIPK1, and SZM-1209 showed high anti-necroptotic activity (EC50 = 22.4 nM) and kinase selectivity on RIPK1 over RIPK3 (Kd,RIPK1 = 85 nM, Kd,RIPK3 > 10,000 nM). In a mTNF-α-induced systemic inflammatory response syndrome (SIRS) model, SZM-1209 could completely reverse mouse deaths with significant anti-inflammatory effects. Furthermore, in a NNK short-term intratracheal exposure-induced ALI model, SZM-1209 significantly alleviated ALI by reducing pulmonary edema and pathological damage. Collectively, activities of SZM-1209 against RIPK1, necroptosis, SIRS, and ALI warranted further investigation of optimized benzothiazoles as promising lead structures against ALI-related diseases.

Microstructure and Nanoindentation Behavior of FeCoNiAlTi High-Entropy Alloy-Reinforced 316L Stainless Steel Composite Fabricated by Selective Laser Melting.

Selective laser melting (SLM) is one of the metal additive manufactured technologies with the highest forming precision, which prepares metal components through melting powders layer by layer with a high-energy laser beam. The 316L stainless steel is widely used due to its excellent formability and corrosion resistance. However, its low hardness limits its further application. Therefore, researchers are committed to improving the hardness of stainless steel by adding reinforcement to stainless steel matrix to fabricate composites. Traditional reinforcement comprises rigid ceramic particles, such as carbides and oxides, while the research on high entropy alloys as reinforcement is limited. In this study, characterisation by appropriate methods, inductively coupled plasma, microscopy and nanointendation assay, showed that we successfully prepared the FeCoNiAlTi high entropy alloy (HEA)-reinforced 316L stainless steel composites using SLM. When the reinforcement ratio is 2 wt.%, the composite samples show higher density. The SLM-fabricated 316L stainless steel displays columnar grains and it varies to equiaxed grains in composites reinforced with 2 wt.% FeCoNiAlTi HEA. The grain size decreases drastically, and the percentage of the low angle grain boundary in the composite is much higher than in the 316L stainless steel matrix. The nanohardness of the composite reinforced with 2 wt.% FeCoNiAlTi HEA is twice as high as the 316L stainless steel matrix. This work demonstrates the feasibility of using a high-entropy alloy as potential reinforcement in stainless steel systems.

The relationship between the monocyte-to-lymphocyte ratio and osteoporosis in postmenopausal females with T2DM: A retrospective study in Chinese population.

Introduction: The risk of fragility fractures is increased in patients with type 2 diabetes mellitus (T2DM). Many reports indicate that inflammatory and immune responses are associated with osteoporosis and osteopenia. The monocyte-to-lymphocyte ratio (MLR) is a novel potential marker of inflammatory and immune responses. The present study evaluated the associations between the MLR and osteoporosis in postmenopausal females with T2DM. Methods: Data were obtained from 281 T2MD postmenopausal females, and divided into three groups: Osteoporosis group, osteopenia group and normal BMD group. Result: Data analyses revealed that the MLR was significantly lower in T2MD postmenopausal females with osteoporosis than in those with osteopenia and normal BMD. Logistic regression showed that the MLR was an independent protective factor for osteoporosis in postmenopausal females with T2DM (odds ratio [OR]: 0.015, 95% confidence interval [CI]: 0.000-0.772). Based on the receiver operating characteristic (ROC) curve, the MLR for diagnosing osteoporosis in postmenopausal females with T2DM was projected to be 0.1019, an area under the curve of 0.761 (95% CI: 0.685-0.838), a sensitivity of 74.8% and a specificity of 25.9%. Conclusions: The MLR have a high efficacy in diagnosis for osteoporosis in postmenopausal females with T2DM. MLR have the potential to be used as diagnosis marker for osteoporosis in postmenopausal females with T2DM.

Structure-Based Design of Novel Alkynyl Thio-Benzoxazepinone Receptor-Interacting Protein Kinase-1 Inhibitors: Extending the Chemical Space from the Allosteric to ATP Binding Pockets.

Systemic inflammatory response syndrome (SIRS), characterized by severe systemic inflammation, represents a major cause of health loss, potentially leading to multiple organ failure, shock, and death. Exploring potent RIPK1 inhibitors is an effective therapeutic strategy for SIRS. Recently, we described thio-benzoxazepinones as novel RIPK1 inhibitors and confirmed their anti-inflammatory activity. Herein, we further synthesized novel thio-benzoxazepinones by introducing substitutions on the benzene ring by an alkynyl bridge in order to extend the chemical space from the RIPK1 allosteric to ATP binding pockets. The in vitro cell and kinase assays found that compounds 2 and 29 showed highly potent activity against necroptosis (EC50 = 3.7 and 3.2 nM) and high RIPK1 inhibitory activity (Kd = 9.7 and 70 nM). Prominently, these two analogues possessed better in vivo anti-inflammatory effects than the clinical candidate GSK'772 and effectively blocked hypothermia and deaths in a TNFα-induced SIRS model.

Plasmacytoma variant translocation 1 inhibits miR-515-5p function and modulates high mobility group B3 to promote the growth of prostate cancer cells.

AIM: This study is performed to analyze the role of long non-coding RNA plasmacytoma variant translocation 1 in prostate cancer. METHODS AND MATERIALS: Plasmacytoma variant translocation 1, miR-515-5p, and high mobility group B3 mRNA expressions were examined using quantitative real-time polymerase chain reaction and immunohistochemistry. After gain-of-function and loss-of-function models were established, the changes in cell proliferation, migration, and invasion were evaluated using cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and Transwell experiments. Validation of the targeting relationships between plasmacytoma variant translocation 1 and miR-515-5p, and between miR-515-5p and high mobility group B3 was conducted using bioinformatics prediction, a dual-luciferase reporter assay, and an RNA immunoprecipitation experiment. Moreover, the effects of plasmacytoma variant translocation 1 and miR-515-5p on high mobility group B3 protein expression were examined using Western blot. RESULTS: Plasmacytoma variant translocation 1 expression and high mobility group B3 expression were up-regulated in prostate cancer tissues and cell lines while miR-515-5p expression was down-regulated. Plasmacytoma variant translocation 1 knockdown restrained the proliferation, migration, and invasion of LNCaP and DU145 cells in vitro, and the transfection with miR-515-5p inhibitors reversed these effects. Mechanistically, plasmacytoma variant translocation 1 could repress the function of miR-515; high mobility group B3 was proved to be a target gene of miR-515-5p, and its expression could be indirectly positively modulated by plasmacytoma variant translocation 1. CONCLUSION: Plasmacytoma variant translocation 1 accelerates prostate cancer progression by repressing miR-515-5p's function to upregulate high mobility group B3 expression.

Dual-targeted repetitive transcranial magnetic stimulation modulates brain functional network connectivity to improve cognition in mild cognitive impairment patients.

Background: Mild cognitive impairment (MCI) is a condition between normal aging and dementia; nearly 10-15% of MCI patients develop dementia annually. There are no effective interventions for MCI progression. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has attempted to improve the overall cognitive function of MCI patients. However, it does not affect episodic memory improvement. Methods: In this study, we engaged 15 clinically diagnosed MCI patients and normal controls to explore the effect of dual-targeted rTMS on progressing cognitive function, particularly episodic memory in MCI patients. Resting-state EEG recordings and neuropsychological assessments were conducted before and after the intervention. EEG features were extracted using an adaptive algorithm to calculate functional connectivity alterations in relevant brain regions and the mechanisms of altered brain functional networks in response to dual-target rTMS. Results: The study revealed that the functional brain connectivity between the right posterior cingulate gyrus (PCC) and the right dorsal caudate nucleus (DC) was significantly reduced in MCI patients compared to normal controls (p < 0.001). Dual-target rTMS increased the strength of the reduced functional connectivity (p < 0.001), which was related to cognitive enhancement (p < 0.05). Conclusion: This study provides a new stimulation protocol for rTMS intervention. Improving the functional connectivity of the right PCC to the right DC is a possible mechanism by which rTMS improves overall cognitive and memory function in MCI patients.

Trypoxylus dichotomus Gut Bacteria Provides an Effective System for Bamboo Lignocellulose Degradation.

Fast-growing bamboo may be a source of high-quality cellulose with the potential to contribute to energy sustainability, if an efficient and low-cost solution to bamboo cellulose decomposition can be developed. This study compared the gut microbiomes of rhinoceros beetle (Trypoxylus dichotomus) feeding on bamboo and wood fiber. The results revealed that diet has a distinctive effect on microbial composition in the midgut, including its most abundant microorganisms that in the fermentation and chemoheterotroph pathways. After identifying the 13 efficient bacterial isolates, we constructed a natural bacterial system based on the microbial relative abundance and an artificial bacterial system with equal proportions of each isolate to catabolize bamboo lignocellulose. The isolate Enterobacter sp. AZA_4_5 and the natural system showed higher degradation efficiency than other single strains or the artificial system. The results can thus serve as important reference for further research and development of a synthetic bacterial consortium to maximize lignocellulolytic ability. IMPORTANCE Bamboo produces a great yield of lignocellulosic biomass due to its high efficiency in carbon fixing. The gut microbiome of Trypoxylus dichotomus differed between bamboo and wood fiber diets. The lignocellulosic pathways were enriched in the gut bacteria of the bamboo diet. The highly efficient bacterial isolates were identified from midgut, whereas the natural bacterial system as well as one isolate showed the higher degradation efficiency of bamboo lignocellulose. The results indicate that the gut bacteria could provide an effective system to utilize the bamboo lignocellulosic biomass.

The impacts of donor transitions on health systems in middle-income countries: a scoping review.

As countries graduate from low-income to middle-income status, many face losses in development assistance for health and must 'transition' to greater domestic funding of their health response. If improperly managed, donor transitions in middle-income countries (MICs) could present significant challenges to global health progress. No prior knowledge synthesis has comprehensively surveyed how donor transitions can affect health systems in MICs. We conducted a scoping review using a structured search strategy across five academic databases and 37 global health donor and think tank websites for literature published between January 1990 and October 2018. We used the World Health Organization health system 'building blocks' framework to thematically synthesize and structure the analysis. Following independent screening, 89 publications out of 11 236 were included for data extraction and synthesis. Most of this evidence examines transitions related to human immunodeficiency virus/Acquired Immune Deficiency Syndrome (AIDS; n = 45, 50%) and immunization programmes (n = 14, 16%), with a focus on donors such as the Global Fund to Fight AIDS, Tuberculosis and Malaria (n = 26, 29%) and Gavi, the Vaccine Alliance (n = 15, 17%). Donor transitions are influenced by the actions of both donors and country governments, with impacts on every component of the health system. Successful transition experiences show that leadership, planning, and pre-transition investments in a country's financial, technical, and logistical capacity are vital to ensuring smooth transition. In the absence of such measures, shortages in financial resources, medical product and supply stock-outs, service disruptions, and shortages in human resources were common, with resulting implications not only for programme continuation, but also for population health. Donor transitions can affect different components of the health system in varying and interconnected ways. More rigorous evaluation of how donor transitions can affect health systems in MICs will create an improved understanding of the risks and opportunities posed by donor exits.

Crystallography-Guided Optimizations of the Keap1-Nrf2 Inhibitors on the Solvent Exposed Region: From Symmetric to Asymmetric Naphthalenesulfonamides.

Directly inhibiting the Keap1-Nrf2 protein-protein interaction has been investigated as a promising strategy to activate Nrf2 for anti-inflammation. We previously reported a naphthalensulfonamide Keap1-Nrf2 inhibitor NXPZ-2, but have not determined the exact binding mode with Keap1. This symmetric naphthalenesulfonamide compound has relatively low solubility. Herein, we first determined a crystal complex (resolution: 2.3 Å) of human Keap1 Kelch domain with NXPZ-2. Further optimizations on the solvent exposed region obtained asymmetric naphthalenesulfonamides and three crystal structures of Keap1 in complex with designed compounds. Among them, the asymmetric piperazinyl-naphthalenesulfonamide 6k with better aqueous solubility showed the best KD2 value of 0.21 µM to block the interaction. The productions of ROS and NO and the expression of TNF-α were inhibited by 6k in the in vitro model. This compound could relieve inflammations by significantly increasing the Nrf2 nuclear translocation in the LPS-induced ALI model with promising pharmacokinetic properties.

Regulation pore size distribution for facilitating malachite green removal on carbon foam.

Malachite green (MG) is widely used as a textile dye and an aquacultural biocide, and become a serious pollution of drink water, but effectually isolating and removing it from wastewater are still a challenge. Here we report a new strategy to prepare a carbon foam with tunable pore size distribution by a one-pot lava foam process. We find that uniform micropore size is beneficial to the formation of C-OH coordination on the pore surface, increasing MG adsorption rates via H+ ionization. As a result, carbon foam with uniform pore size distribution demonstrates an optimum MG removal efficiency of 1812 mg g-1 and a higher partition coefficient of 3.02 mg g-1 µM-1, which is twice that of carbon foams with irregular pore size distribution. The adsorption of MG onto these adsorbents was found to be an endothermic monolayer chemical adsorption process, and the Gibbs free energy of adsorption process was decreased obviously by regulating micropore size distribution. The experiment results are in good agreement with pseudo-second-order kinetic and Langmuir isotherm models. Revealed the pore size distribution was the critical factor of MG removal by carbon foam. It should be and inspiration for the design and development of highly efficiency adsorbents for dyes removal.

Enhancement of Upconversion Luminescence by the Construction of a 3Yb-Er-Hf Sublattice Energy Cluster and Surface Defect Elimination.

Nanotetragonal LiYF4:RE (Tm,Er,Ho) is a kind of excellent upconversion luminescence (UCL) material potentially used in many fields, while the enhancement of UC emission and regulation of luminescence lifetime are still a challenge. Herein, a strategy was reported to enhance UCL performance with the aid of the construction of a 3Yb-Er-Hf sublattice energy cluster with the introduction of Hf4+ and the interception of surface defect fluorescence quenching. UCL was obviously decreased by Hf4+ doping without surface defect elimination, but after the interception of surface defect quenching, UCL was dramatically enhanced more than 300-fold with an Er3+/Hf4+ mole ratio of 1:1. The contribution of UCL enhancement by the construction of a 3Yb-Er-Hf sublattice energy cluster is about 1.5 times of the sample without energy cluster construction. Interestingly, the lifetime of UCL can also be regulated by this strategy. According to the results of systematical microstructure analyses and UCL performance behaviors examined by X-ray powder diffraction (XRD), small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), and fluorescence spectrophotometry (FS) methods, the possible mechanism of UCL enhancement was proposed. This work may be an inspiration for researchers to design and develop high-performance UCL nanomaterials.

TRAF7 contributes to tumor progression by promoting ubiquitin-proteasome mediated degradation of P53 in hepatocellular carcinoma.

It has been proved that TRAFs family proteins played malfunctioning roles in the development of human cancers. TRAF7 is the last one of TRAFs family proteins to be found, which was demonstrated to be involved in a serious of cancers development. In this study, we systematically investigated the molecular mechanisms of TRAF7 in facilitating hepatocellular carcinoma (HCC). We discovered that TRAF7 was overexpressed in tumor tissues and the increased TRAF7 expression was closely associated with tumor size, histologic grade, TNM stage and poor prognostication. TRAF7 overexpression repressed cell apoptosis and promoted cell proliferation, invasion and migration, whereas knockdown of TRAF7 in HCC cells had totally opposite effects. Besides, we identified the interaction between TRAF7 and P53 in HCC and demonstrated that TRAF7 promoted ubiquitin-proteasome mediated degradation of P53 at K48 site. The rescue assays further proved that the function of TRAF7 in inhibiting apoptosis and promoting tumor development was depended on P53 in HCC. Overall, this work identified that TARF7 promoted tumorigenesis by targeted degradation P53 for ubiquitin-mediated proteasome pathway. Targeting the TRAF7-P53 axis may provide new insights in the pathogenesis of HCC, and pave the way for developing novel strategies for HCC prevention and treatment.

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials.

Background: Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects. Methods: Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed. Results: A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44-1.22, p = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48-0.97, p < 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI. Conclusions: This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708.