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The crosstalk between clathrin-mediated endocytosis (CME) and the autophagy pathway has been reported in mammals; however, the interconnection of CME with autophagy has not been established in plants. Here, we report that the Arabidopsis CLATHRIN LIGHT CHAIN (CLC) subunit 2 and 3 double mutant, clc2-1 clc3-1, phenocopies Arabidopsis AUTOPHAGY-RELATED GENE (ATG) mutants in both autoimmunity and nutrient sensitivity. Accordingly, the autophagy pathway is significantly compromised in the clc2-1 clc3-1 mutant. Interestingly, multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific manner. As expected, both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation, and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 mutant. Notably, simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum, supporting the functional relevance of the CLC2-ATG8h/8i interactions. In conclusion, our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

Objective: Standardize the use of phoxim to ensure the safety of aquatic products. Methods: Taking freshwater crucian carp as the research object, Selecting phoxim, an organic phosphorus pesticide often used in agriculture, as the representative of exogenous environmental pollutants. The changes in normal physiological metabolism of crucian carp exposed to phoxim were studied by using the 1H-NMR metabonomics method combined with PCA, PLS-DA, OPLS-DA and other multivariate statistical methods. Based on this, the toxic effects of phoxim on crucian carp and the toxicological mechanism of phoxim in the crucian carp were deduced. Results: Compared with the control group, the metabolites in the crucian carp serum sample of the phoxim group have a significant increase in concentration of 3-HB, glucose and phenylalanine, and a significant decrease of glutamic acid, alanine, asparagine, histidine, lactic acid, glycerol phosphate of choline, phosphoric acid, choline, choline and unsaturated fatty acids, lipids, guanine nucleoside, inosine(P＜0.05). Conclusion: The results showed that phoxim can change amino acid metabolism, energy metabolism, disturbance of neurotransmitter balance and oxidative stress in crucian carp.and the endogenous metabolites change may be related to Ⅱ metabolic reactions of phoxim in crucian carp.

BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common.

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies. [ABSTRACT FROM AUTHOR]

The existing mine ventilator rolling bearing fault diagnosis method only extracts time-frequency component characteristics and adopts shallow network structure, thus causing low fault diagnosis accuracy. In order to solve this problem, a fault diagnosis method of rolling bearing of mine ventilator based on multi-domain characteristic fusion and deep belief network (DBN) is proposed. Firstly, the method performs wavelet packet noise reduction on the bearing vibration signal, and extracts time domain characteristics, frequency domain characteristics and IMF energy characteristics from the bearing vibration signal after noise reduction to obtain a relatively comprehensive set of high-dimensional characteristic set. Secondly, the characteristic selection method based on intra-class and inter-class standard deviation is used to eliminate the characteristics that are not effective for classification and characteristics with no obvious effect so as to filter out high-efficiency characteristics. Finally, kernel principal component analysis (KPCA) is used to reduce and fuse the high-dimensional screening characteristics, eliminate the redundancy between characteristics, and input the fused characteristics into DBN to complete the fault diagnosis. The experimental results show that compared with the diagnosis method based on single characteristic and shallow network, the average accuracy of mine ventilator rolling bearing fault diagnosis method based on multi-domain characteristic fusion and DBN has average accuracy and less average diagnosis time showing good stability and generalization ability for different damage fault data.

In recent years, more attention has been paid to the application of host‐associated microorganisms as an appropriate source of probiotics in aquaculture. These probiotics promoted effective colonization and application and provided better benefits than other sources. A total of 32 isolates were collected from the water, shrimp, and sediment of the cultured pond of Litopenaeus vannamei. Probiotic effects were comprehensively evaluated by extracellular enzyme activity, virulence genes detection, bacteriostatic activity, drug susceptibility test, tolerance to adverse environment, and challenge experiment. Six of these isolates exhibited bacteriostatic activity against pathogens, such as Vibrio cholerae, V. owensii, V. fluvialis, V. campbellii, V. rotiferianus, Photobacterium damselae, V. vulnificus, and V. parahaemolyticus. Using 16S rRNA gene sequencing analysis, isolates were identified as Bacillus subtilis (P8, P29, and P30), B. velezensis (P12), Prestia flexa (P21), and Cytobacillus firmus (P23). They were tolerant to high temperature, low acid (pH 2.0), bile salt (2%), and the simulated gastrointestinal environment, secreting phospholipase, amylase, protease, gelatinase, and lipase. They were sensitive to only two or fewer drugs among 27 antibacterial drugs and did not carry any of the tested virulence genes. Biosafety in vivo evaluations showed that they were safe for Ctenopharyngodon idella (P12 ＞ P23 ＝ P29 ＞ P8 ＞ P30 ＝ P21). The results suggest that P8, P12, P23, P21, P29, and P30 have high probiotic potential and can be used as good probiotics in aquaculture and the development of ecological preparations. [ABSTRACT FROM AUTHOR]

Objective To conduct a comprehensive evaluation of the quality of medical services of second-and third-level specialist hospitals in Chengdu based on CHS-DRG payment data combined with entropy-weighted TOPSIS and RSR methods, in order to provide reference for improving the quality of hospital services and medical technology. Methods The data came from the DRG payment data of Sichuan Medical Insurance Affairs Administration Center in 2021 and thirteen DRGs-related indicators were selected, and the data were analysed and evaluated by using the entropy-weighted TOPSIS and RSR methods to assign weights to the indicators, and the evaluation results were graded. Results The top 3 indicator weights were the proportion of level 4 surgeries (23.5%), inpatient services (21. 2%) and level 3 surgeries (14. 9%), and the top 3 hospitals in terms of quality of medical services were A2, A3 and B4. From the staging results: staging 1 included 6 hospitals such as A13 B8 and B21, staging 2 included 31 hospitals such as A12, B17 and A1 and the 3rd slot included 7 hospitals such as A2, A3 and B4. Conclusion There are significant differences in the quality of medical services between different types and levels of specialist hospitals in Chengdu. In evaluating different types of specialist hospitals, we need to combine the characteristics of their specialties and select evaluation indicators scientifically. In general, improving the capacity of medical services is the key to achieving high-quality development of specialist hospitals. [ABSTRACT FROM AUTHOR]

This paper presents a heuristic contraflow-based reconfiguration evacuation algorithm, which is named Capacity-Constrained Contraflow Adaption (CC-Adap). First, it effectively calculates optimal candidate routes for evacuation. Second, an evaluation method is proposed for estimating these candidate routes. Third, CC-Adap utilizes a contraflow-based method to reconfigure the evacuation routes to improve capacity constraints. Fourth, traffic conditions are updated in real time. Fifth, CC-Adap reuses historical evacuation routes to reduce the computational cost and accelerate the evacuation process. Experimental results show that CC-Adap generates high-performing evacuation strategies and can be used to tackle large-scale evacuation planning.

E3 ubiquitin ligases play essential roles in plant defense responses. However, their roles in other plant species have not been investigated extensively. Here, we used a gain-of-function approach to interrogate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybeans. Ectopic over-expression of GmSAUL1a in Nicotiana tabacum resulted in autoimmune responses that could be suppressed by high temperature, which is a hallmark of NLR (nucleotide-binding leucine-rich repeat protein)-mediated resistance. Interestingly, an elevated activation of NtMPK6, but reduced activation of NtMPK4, responding to flg22 treatment, was observed in these GmSAUL1a-over-expressing tobacco lines, suggesting that over-expressing GmSAUL1a activates immune signaling through activating NtMPK6, but suppressing NtMPK4 kinase activity. Collectively, these results demonstrated that GmSAUL1 plays a positive and pivotal role in soybean immunity that is likely governed by NLR proteins. [ABSTRACT FROM AUTHOR]