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Summary: SARM1, an NAD-utilizing enzyme, regulates axonal degeneration. We show that CZ-48, a cell-permeant mimetic of NMN, activated SARM1 in vitro and in cellulo to cyclize NAD and produce a Ca2+ messenger, cADPR, with similar efficiency as NMN. Knockout of NMN-adenylyltransferase elevated cellular NMN and activated SARM1 to produce cADPR, confirming NMN was its endogenous activator. Determinants for the activating effects and cell permeability of CZ-48 were identified. CZ-48 activated SARM1 via a conformational change of the auto-inhibitory domain and dimerization of its catalytic domain. SARM1 catalysis was similar to CD38, despite having no sequence similarity. Both catalyzed similar set of reactions, but SARM1 had much higher NAD-cyclizing activity, making it more efficient in elevating cADPR. CZ-48 acted selectively, activating SARM1 but inhibiting CD38. In SARM1-overexpressing cells, CZ-48 elevated cADPR, depleted NAD and ATP, and induced non-apoptotic death. CZ-48 is a specific modulator of SARM1 functions in cells. : Biochemistry; Enzymology; Biochemical Mechanism Subject Areas: Biochemistry, Enzymology, Biochemical Mechanism

Purpose Ethics review processes have become increasingly complex. The objective of this study was to explore the challenges currently faced in ethics reviews of clinical scientific research projects in China, with the goal of standardizing the structure of medical ethics committees and better protecting the rights and interests of research participants. Methods We reviewed and comprehensively analyzed the available literature discussing standardized ethics reviews of clinical scientific research projects. Results We identified the following problems: incomplete legislation, absence of supervision, vague review criteria, limitations of ethics committee competence, inadequate ethics consciousness, and poor tracking of reviews. In this paper, we suggest strategies for the development of future ethical reviews of clinical scientific research projects. Conclusion To standardize the ethics review process of clinical scientific research projects in China, it is necessary to establish relevant laws and regulations and implement supervisory responsibilities. Professional training of medical ethics committees is suggested as an effective way to improve the quality of ethics reviews.

Genetically modified crops which had been commercial applied extensively majorly are the insect resistance and herbicide tolerance events. In this study, the Bt insecticidal gene Cry1Ab, the glyphosate-tolerant gene EPSPS, and the selection marker gene PMI were combined into a single transferred DNA fragment and introduced into sugarcane by Agrobacterium-mediated transformation. Thirty-three resistant plantlets were obtained after selection using a PMI/mannose selection system. Thirty of these resistant plantlets were PCR positive for the three target genes. Southern blot assay revealed that the copy number of the integrated fragment in the transformed plantlets varied from 1 to 7. ELISA analysis showed that 23 of the 33 resistant plantlets expressed Cry1Ab and EPSPS protein. Five single-copy and ELISA-positive transgenic lines were tested under laboratory and field conditions to determine their resistance to insects and herbicides, and also evaluated their agronomic characteristics and industrial traits. Results showed that larvae fed with fodder mixture containing stem tissues from single-copy transgenic lines were weak and small, moreover, pupation and eclosion were delayed significantly during voluntary feeding bioassays. None of transgenic sugarcane was destroyed by cane borer while more than 30% of wild type sugarcane was destroyed by cane borer. For herbicide resistance, the transgenic plantlets grew healthy even when treated with up to 0.5% roundup while wild type plantlets would die off when treated with 0.1% roundup. Thus demonstrate that these transgenic lines showed strong insect resistance and glyphosate tolerance under both laboratory and field conditions. But in the field most of the transgenic plants were shorter and more slender than non-transformed control plants. So they presented poor agronomic characteristics and industrial traits than non-transformed control plants. Thus, a considerable number of embryogenic calli should be infected to obtain transgenic lines with potential for commercial use.

This paper focuses on a multiproject resource allocation problem in a bilevel organization. To solve this problem, a bilevel multiproject resource allocation model under a fuzzy random environment is proposed. Two levels of decision makers are considered in the model. On the upper level, the company manager aims to allocate the company's resources to multiple projects to achieve the lowest cost, which include resource costs and a tardiness penalty. On the lower level, each project manager attempts to schedule their resource-constrained project, with minimization of project duration as the main objective. In contrast to prior studies, uncertainty in resource allocation has been explicitly considered. Specifically, our research uses fuzzy random variables to model uncertain activity durations and resource costs. To search for the optimal solution of the bilevel model, a hybrid algorithm made up of an adaptive particle swarm optimization, an adaptive hybrid genetic algorithm, and a fuzzy random simulation algorithm is also proposed. Finally, the efficiency of the proposed model and algorithm is evaluated through a practical case from an industrial equipment installation company. The results show that the proposed model is efficient in dealing with practical resource allocation problems in a bilevel organization.

Sugarcane, a vital cash crop, contributes significantly to the world’s sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.

Objective: The purpose of this study was to analyze the impact of Shaoyao-Gancao decoction (SGD) on proteins with significant changes in the dorsal root ganglion (DRG) in rats and to explore the role of the Semaphorin 3G (Sema3G) protein in the DRG and its downstream factors, interleukin-6 (IL-6) and CC-motif chemokine ligand 2(CCL2), in the treatment of chronic inflammatory pain (CIP). Methods: We created a CIP rat model using 100 μL of complete Freund's adjuvant (CFA) that was injected into the left posterior plantar of rats. Then, we administered SGD intragastrically. We tested the animals for behavioral changes and protein expression levels in DRG pre- and post-drug intervention. Results: Rats in the SGD group showed significantly increased paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and relative expression levels of the Sema3G protein in the DRG (all P

Laser manipulation of nuclear decay has extremely promising applications. In this study, cutting-edge Gaussian lasers were combined with the latest data on α decay to thoroughly investigate the factors that impact the penetration probability in laser-assisted α decay of nuclei, while considering the deformation of the nucleus. Our calculations reveal that using state-of-the-art laser fields can marginally alter the half-life of α decay by affecting the penetration probability within a narrow range. Moreover, our findings demonstrate two key points: (1) By deriving an analytical formula for the rate of change of the α decay penetration probability in an ultra-intense laser field, we unveil the negative correlation between the α decay energy and the rate of change of the α decay penetration probability. (2) We attribute the wavelength as the determinant of the effect of the average rate of change of the penetration probability, which we explain by reconstructing the laser pulse width and wavelength. This research offers a rapid method to estimate the rate of change of the α-decay penetration probability and serves as a valuable reference for future experimental investigations of laser-nuclear interactions.

ABSTRACT Cognitive dysfunction is a common symptom experienced by elderly individuals after surgery, resulting in memory problems, difficulties with logical thinking, hallucinations, delusions, and an increased risk of dementia. Despite its prevalence, the underlying cause of postoperative cognitive dysfunction remains unclear. Recent research has uncovered a link between neurodegenerative diseases and the gut microbiota, indicating the need for further investigation into the role of the intestinal flora in postoperative cognitive dysfunction. To address this research gap, we conducted behavioral tests, gene and protein analyses, metagenomics, and non-targeted metabolomics to compare the gut microbiota and metabolomics of mice exposed to anesthesia/surgery that exhibited cognitive impairment with those of age-matched control mice. Our goal was to identify possible correlations between these factors. We found that mice experiencing postoperative cognitive dysfunction had a distinct microbial composition, neuroinflammation, and synaptic damage compared to the control group. Specifically, we observed significant increases in the relative abundances of Bacteroidetes unclassified, Bacteroides acidifaciens, Rikenellaceae bacterium, Muribaculaceae bacterium Isolate-104 HZI, Muribaculaceae bacterium Isolate-110 HZI, and Mucispirillum schaedleri in aged mice exposed to anesthesia and surgery, while the relative abundances of Lachnospiraceae bacterium A2, Lachnospiraceae bacterium A4, Lachnospiraceae bacterium, Blautia, Lachnoclostridium bacterium MD355, Eubacterium rectale, Ruminococcus sp. 1xD21-23, and Butyrivibrio were significantly decreased. Additionally, metabolites, such as thiamine, spermidine, and long-chain unsaturated fatty acids, were down-regulated compared to the control group. These findings suggest that the intestinal metabolic abnormalities observed in elderly mice exposed to anesthesia/surgery may be regulated by the intestinal microbiota, specifically the Lachnospiraceae, Lachnoclostridium, Butyrivibrio, and Eubacterium. Therefore, our study highlights the potential of manipulating the gut microbiota to modulate the host metabolism in order to prevent and manage postoperative cognitive dysfunction. IMPORTANCE As the population ages and medical technology advances, anesthesia procedures for elderly patients are becoming more common, leading to an increased prevalence of postoperative cognitive dysfunction. However, the etiology and correlation between the gut microbiota and cognitive dysfunction are poorly understood, and research in this area is limited. In this study, mice with postoperative cognitive dysfunction were found to have reduced levels of fatty acid production and anti-inflammatory flora in the gut, and Bacteroides was associated with increased depression, leading to cognitive dysfunction and depression. Furthermore, more specific microbial species were identified in the disease model, suggesting that modulation of host metabolism through gut microbes may be a potential avenue for preventing postoperative cognitive dysfunction.

α-Linolenic acid (ALA) is an important nutrient component in rapeseed oil, and rapeseed breeders want to either restrain or enhance the function of fatty acid desaturases (FADs) in the ALA biosynthesis pathway. To determine the reason for the upregulation of rapeseed BnFAD genes in two high-ALA accessions, R8Q10 and YH25005, we compared their transcriptome profiles in the seed at 24 days after pollination (DAP) with those of two low-ALA lines, A28 and SW. The expression levels of twenty-eight important genes in the seed samples at 20, 27, and 34 DAP were also investigated using an RT-qPCR. The expression levels of genes involved in flavonoid and proanthocyanidin synthesis, including BnCHS, BnCHI, BnDFR, BnFLS1, BnLDOX, BnBAN, BnTT10, and BnTT12 and genes encoding the transcription factors BnTT1, BnTT2, BnTT8, and BnTT16 were lower in R8Q10 and YH25005 than in A28 and SW. The expression levels of genes encoding master transcription factors in embryo development, such as BnLEC1, BnABI3, BnFUS3, BnL1L, BnAREB3, and BnbZIP67, were elevated significantly in the two high-ALA accessions. Combined with previous results in the Arabidopsis and rapeseed literature, we speculated that the yellow-seededness genes could elevate the activity of BnLEC1, BnABI3, BnFUS3, and BnbZIP67, etc., by reducing the expression levels of several transparent testa homologs, resulting in BnFAD3 and BnFAD7 upregulation and the acceleration of ALA synthesis. Yellow-seededness is a favorable factor to promote ALA synthesis in the two high-ALA accessions with the yellow-seeded trait. These findings provide initial insights into the transcriptomic differences between high-/low-ALA germplasms and a theoretic basis for seed quality breeding.

Objective To study the dynamic changes of left ventricular hypertrophy with age found in spontaneously hypertensive rats (SHR). Methods Forty-five male SHR and thirty-five male Wistar Kyoto rats (WKY), which were four-week-old and specific-pathogen free, were observed continuously for 42 weeks. At 6,8,12,18,24,32 and 42 weeks of age, cardiac structure and function were examined by echocardiography, and systolic blood pressure was measured by tail cuff method; At the same time points, left ventricular mass index (LVMI) was calculated. The morphology of left ventricle was microscopied by HE staining, genes ANP and β-MHC were detected by RT-qPCR. Results The systolic blood pressure of SHR increased rapidly during the period from 6th to 12th weeks, and was significantly higher than that of WKY at 12 weeks (P＜0.05), after that the blood pressure of SHR increased slightly and slowly. With age and blood pressure changes, left ventricular hypertrophy gradually developed in SHR.The related hypertrophic indexes,interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT),transverse diameter of myocardial cell (TDM) and LVMI all showed characteristic changes. Correspondingly, the expression of hypertrophy-related genes ANP and β-MHC in SHR showed age- and blood pressure-dependent dynamic changes. Conclusions The left ventricular hypertrophy in SHR is characterized by the dynamic changes with aging and change of blood pressure.

In the course of decomposing and enhancing the low-light images with Retinex model,it needs to manually adjust the parameters continuously to reach the optimal solution,which will reduce the efficiency of the entire process.In addition,existing low-light image enhancement methods based on Retinex fail to take both reflectance and illumination into account when perfor-ming image enhancement,and there are problems such as too much noise in the reflectance of low-light image,low brightness and not enough prominent details in the illumination.Aiming to solve these problems,a data-driven deep network is proposed to learn the decomposition and the enhancement of the low-light images,and the model parameters are learned through the end-to-end network training.The network firstly decomposes the low-light images into the reflectance and the illumination.Aiming at the problem of high noise in the reflectance,an improved denoising convolutional neural network model NDnCNN is used for denoising,and aiming at the problems of low brightness and not enough prominent details in the illumination,we introduce the convolutional block attention model CBAM to enhance the details and guide the network to modify the illumination.Finally,the denoised reflectance and the modified illumination are used for image reconstruction.Experimental results show that the enhanced low-light image is more photo-realistic with increased brightness,prominent details,rich information and low image distortion.

Composition analysis in wine is gaining increasing attention because it can provide information about the wine quality, source, and nutrition. In this work, in situ liquid secondary ion mass spectrometry (SIMS) was applied to 14 representative wines, including six wines manufactured by a manufacturer in Washington State, United States, four Cabernet Sauvignon wines, and four Chardonnay wines from other different manufacturers and locations. In situ liquid SIMS has the unique advantage of simultaneously examining both organic and inorganic compositions from liquid samples. Principal component analysis (PCA) of SIMS spectra showed that red and white wines can be clearly differentiated according to their aromatic and oxygen-contained organic species. Furthermore, the identities of different wines, especially the same variety of wines, can be enforced with a combination of both organic and inorganic species. Meanwhile, in situ liquid SIMS is sample-friendly, so liquid samples can be directly analyzed without any prior sample dilution or separation. Taken together, we demonstrate the great potential of in situ liquid SIMS in applications related to the molecular investigation of various liquid samples in food science.

BackgroundPrevious studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates.MethodsPatients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions.ResultsMultivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction 65 years old. This result was confirmed by trend analysis (P for trend 65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.