Search

Background: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. Methods: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H 2 S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H 2 S system and the findings were confirmed in transgenic mice. Results: Higher plasma H 2 S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1–nucleosome remodeling and deacetylase) to repress the transcription of CTH , the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H 2 S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD. Conclusions: Decreased plasma H 2 S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH , impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression.

We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-β signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.

An environmentally friendly strategy for the photo-catalyzed three-component reaction between quinoxalin-2(1H)-ones, vinylarenes, with inexpensive and easily accessible ethyl bromodifluoroacetate/sodium difluoromethanesulfinate is described. This protocol exhibits mild conditions, high efficiency, and excellent functional group tolerance, providing a highly efficient approach for the synthesis of difluorobenzylated quinoxalin-2(1H)-ones by the formation of two carbon-carbon bonds. A radical mechanism is responsible for this three-component transformation.

The Y3Al5-xNbxO12 (0 ≤ x ≤ 0.06) garnet ceramics were prepared by solid-state reaction method. The effects of Nb5+ substitution on the phase composition, microstructure and microwave dielectric properties were investigated. All samples retained the yttrium-aluminum garnet solid solution form until x up to 0.06 at which YNbO4 secondary phase precipitated. The doping of Nb2O5 improved the grain development and enhanced the physical properties of the ceramics under the sintering condition of 8 h at 1700 °C. Specifically, with the substitution of Nb5+, the degree of micromorphology improvement and quality factor first increased and then decreased, with a maximum value at x = 0.015. Finally, the best combination of microwave dielectric properties was obtained, i.e., εr = 10.79, Q×f = 165,478 GHz, τf = -31.7 ppm/°C. This study provides a theoretical basis for the further expansion and application of yttrium aluminum garnet in the microwave field. Keywords: Yttrium Aluminum Garnet ceramics, Nb2O5, microwave dielectric properties.

Although salinity satellites can provide high-resolution global sea surface salinity (SSS) data, the satellite data still display large errors close to the coast. In this paper, a nonlinear empirical method based on random forest is proposed to correct two Soil Moisture and Ocean Salinity (SMOS) L3 products in the tropical Indian Ocean, including SMOS BEC and SMOS CATDS data. The agreement between in-situ data and the corrected SMOS data is better than that between in-situ data and the original satellite data. The root-mean-square deviation (RMSD) of the satellite SSS data decreased from 0.366 to 0.275 and from 0.367 to 0.255 for SMOS BEC and SMOS CATDS, respectively. The effect of the correction model was better in the Arabian Sea than in the Bay of Bengal. The RMSD of corrected BEC (CATDS) SSS was reduced from 0.44 (0.48) to 0.276 (0.269), and the correlation coefficient was increased to 0.915 from 0.741(0.801) in the Arabian Sea while the correlation coefficient improved less than 0.02 in the Bay of Bengal. The cross-validation results highlight the robustness and effectiveness of the correction model. Additionally, the effects of different features on the correction model are discussed to demonstrate the vital role of geographical information in the correction of satellite SSS data. The proposed method outperformed other machine-learning methods with respect to the RMSD and correlation coefficient.

A convenient and efficient copper-catalyzed oxidative C3-cyanoarylation of quinoxalin-2(1H)-ones is developed using 3-aminoindazoles as efficient arylating agents via the cleavage of two C–N bonds.

There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis.Twenty-four 5-week-old lipoprotein E knockout (apoEAlterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p .05), which were positively correlated with serum TMAO levels (p .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p .05).Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.

Ammonia as a carbon-free fuel used in IC engines always suffers from large cyclic variations and high NOx emissions. Ammonia blending with high-reactivity fuels is recognized as an effective attempt to overcome these shortcomings. In this work, for the first time, the combustion and emission characteristics of n-heptane/ammonia were investigated under reactivity-controlled compression ignition (RCCI) conditions in an optical engine. An intake adapter was introduced to modify turbulent flow motion and n-heptane was directly injected to regulate mixture reactivity based on energy ratios. Particle image velocimetry (PIV) was employed for in-cylinder flow measurement, high-speed photography and instantaneous pressure acquisition were used for combustion evolutions, and Fourier transform infrared (FTIR) spectroscopy was adopted for NOx and NH3 emissions. The results show both mixture reactivity and turbulence have significant impacts on ammonia combustion. Specifically, n-heptane addition manifesting mixture reactivity dominates combustion processes at early-injection conditions, while the turbulence with increasing intensity becomes significant at late-injection conditions. Visualization images show that the initiation of initial flame kernels is controlled by the local distribution of n-heptane fraction, and that high n-heptane fraction at early injection or low n-heptane fraction at late injection conditions tends to induce homogeneous combustion. Flame stretch analysis confirms the promotion of mixture reactivity and turbulence motion on turbulent flame propagation and identifies that a high n-heptane fraction with swirl-tumble motion exhibits lower flame stretch sensitivity, especially for late-injection scenarios. Besides, low mixture reactivity with early injection and high mixture reactivity with late injection strategies can achieve high-efficiency combustion. However, when considering NOX/NH3 emissions, a high n-heptane fraction at late injection with swirl-tumble motion has the most potential to achieve the compromise between thermal efficiency and emissions. The present work demonstrates that with optimized fuel injection and flow arrangement, ammonia blending with high-reactivity fuels can achieve high-efficient combustion while maintaining NOx/NH3 emissions within reasonable levels.

The goal is to propose an effective method for locating a fault segment in urban power distribution networks. Urban distribution networks have multiple outgoing lines, switches with multiple connections and have variable topology characteristics. It is found that the fault location method based on matrix algorithm has low adaptive capability and fault tolerance when dealing with complex and variable topology. Therefore, this paper proposes an efficient fault segment location method based on special fault indicators, which can significantly improve the accuracy and reliability of fault location. Accordingly, to improve the accuracy and reliability of fault location, a fault segment location method based on fault marking is proposed. The approach proposed in the paper relies on the analysis of the incident matrix, which describes the relationship between nodes and branches, and allows the use of graph theory. The branch state vector is added to obtain the adjacency matrix, which allows to describe the state of change in the dynamics of the distribution network topology. In the next step, a set of nodes and branches, which reflect the incoming and outgoing interconnections of the nodes, is established based on the selected direction of the network binding. According to the direction of the node fault current, the suspicious branches are identified and labeled to indicate the fault. By cumulative calculation and analysis of the labels, the target branches are screened out and the faulty sections of the city power supply network are identified. The results of the case study conducted in the paper show that the proposed method has good adaptability to the variable topology and increases the fault tolerance and accuracy of the developed matrix algorithm. The topological operating state of the network can be changed by controlling the switches to optimize the operation and improve the reliability of the power supply. Thus, the algorithm for fast and accurate fault location is of great importance for improving the safety and quality of urban power supply.

It is a critical impact on the processing of biological cells to protein–protein interactions (PPIs) in nature. Traditional PPIs predictive biological experiments consume a lot of human and material costs and time. Therefore, there is a great need to use computational methods to forecast PPIs. Most of the existing calculation methods are based on the sequence characteristics or internal structural characteristics of proteins, and most of them have the singleness of features. Therefore, we propose a novel method to predict PPIs base on multiple information fusion through graph representation learning. Specifically, firstly, the known protein sequences are calculated, and the properties of each protein are obtained by k-mer. Then, the known protein relationship pairs were constructed into an adjacency graph, and the graph representation learning method–graph convolution network was used to fuse the attributes of each protein with the graph structure information to obtain the features containing a variety of information. Finally, we put the multi-information features into the random forest classifier species for prediction and classification. Experimental results indicate that our method has high accuracy and AUC of 78.83% and 86.10%, respectively. In conclusion, our method has an excellent application prospect for predicting unknown PPIs.

Fine-root decomposition is a critical process regulating ecosystem carbon cycles and affecting nutrient cycling and soil fertility. However, whether interaction between warming and grazing affects fine-root decomposition is still under-researched in natural grasslands. A two-factorial experiment with asymmetric warming (i.e. daytime vs. nighttime and growing season vs. nongrowing season) and moderate grazing (i.e. about average 50% forage utilization rate) was conducted to explore whether warming and grazing affect fine-root decomposition and loss of nutrients during a 2-year decomposition period in an alpine meadow on the Tibetan Plateau. Both warming and grazing facilitated carbon cycling through increase in fine-root decomposition, and influenced element cycling which varies among elements. The effects of warming and grazing on fine-root decomposition and loss of nutrients were additive. Both warming and grazing significantly increased cumulative percentage mass loss and total organic carbon loss of fine roots during the 2-year experiment. Only warming with grazing treatment reduced percentage nitrogen loss, whereas warming, regardless of grazing, decreased percentage phosphorus loss. Warming and grazing alone increased percentage loss of potassium, sodium, calcium and magnesium compared with control. There were no interactions between warming and grazing on fine-root decomposition and loss of nutrients. There was greater temperature sensitivity of decreased phosphorus loss than that of decreased nitrogen loss. Different temperature sensitivities of percentage loss of nutrients from fine-root decomposition would alter ratios of the available nutrients in soils, and may further affect ecosystem structure and functions in future warming.

As an evolutionarily conserved DNA-sensing machinery in innate immunity, the cGAS-STING pathway has been reported to play an important role in immune surveillance and tumor suppression. Recent evidence suggests an intriguing tumor- and metastasis-promoting effect of this signaling pathway, either in a cancer cell-autonomous or a cancer cell-nonautonomous, bystander cell-mediated manner. Here, we show a new face of cGAS-STING signaling whose activation in a cancer-cell-autonomous response manner confers drug resistance. Targeted or conventional chemotherapy drug treatment induced cancer cell cytosolic DNA accumulation and triggered subsequent cGAS-STING signaling activation in cancer cell lines and the human cell-derived xenograft tumors. This activation promoted an acquisition and maintenance of drug resistance which was prevented and overcome in vitro and in vivo by blockade of STING signaling. This finding highlights a new face of cGAS-STING signaling and an ability of cancer cells to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress and warrants a caution in combining STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.Statement of significancecGAS-STING signaling has long been recognized as playing a key role in triggering antitumor immunity. We reveal a new face of cGAS-STING signaling and an ability of cancer cells autonomously to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress.

Hypermucoviscosity is a critical virulent factor for Klebsiella pneumoniae infections, and its regulation remains poorly understood at the molecular level. This study aims to address this knowledge gap by investigating the role of response regulators in mediating hypermucoviscosity in K. pneumoniae .

Rose (Rosa hybrida) is one of most famous ornamental plants in the world, and its commodity value largely depends on its flower color. However, the regulatory mechanism underlying rose flower color is still unclear. In this study, we found that a key R2R3-MYB transcription factor, RcMYB1, plays a central role in rose anthocyanin biosynthesis. Overexpression of RcMYB1 significantly promoted anthocyanin accumulation in both white rose petals and tobacco leaves. In 35S:RcMYB1 transgenic lines, a significant accumulation of anthocyanins occurred in leaves and petioles. We further identified two MBW complexes (RcMYB1-RcBHLH42-RcTTG1; RcMYB1-RcEGL1-RcTTG1) associated with anthocyanin accumulation. Yeast one-hybrid and luciferase assays showed that RcMYB1 could active its own gene promoter and those of other EBGs (early anthocyanin biosynthesis genes) and LBGs (late anthocyanin biosynthesis genes). In addition, both of the MBW complexes enhanced the transcriptional activity of RcMYB1 and LBGs. Interestingly, our results also indicate that RcMYB1 is involved in the metabolic regulation of carotenoids and volatile aroma. In summary, we found that RcMYB1 widely participates in the transcriptional regulation of ABGs (anthocyanin biosynthesis genes), indicative of its central role in the regulation of anthocyanin accumulation in rose. Our results provide a theoretical basis for the further improvement of the flower color trait in rose by breeding or genetic modification.

Swarm aerial robots are required to maintain close proximity to successfully traverse narrow areas in cluttered environments. However, this movement is affected by the downwash effect generated by the other quadrotors in the swarm. This aerodynamic effect is highly nonlinear and hard to model by classic mathematical methods. In addition, the motor speeds of quadrotors are risky to reach the limit when resisting the effect. To solve these problems, we integrate a Neural network Downwash Predictor with Nonlinear Model Predictive Control (NDP-NMPC) to propose a trajectory-tracking approach. The network is trained with spectral normalization to ensure robustness and safety on uncollected cases. The predicted disturbances are then incorporated into the optimization scheme in NMPC, which handles constraints to ensure that the motor speed remains within safe limits. We also design a quadrotor system, identify its parameters, and implement the proposed method onboard. Finally, we conduct an open-loop prediction experiment to verify the safety and effectiveness of the network, and a real-time closed-loop trajectory tracking experiment which demonstrates a 75.37% reduction of tracking error in height under the downwash effect., 8 pages, 8 figures. Submitted to CDC 2023

Directed energy deposition is a typical laser remanufacturing technology, which can effectively repair failed parts and extend their service life, and has been widely used in aerospace, metallurgy, energy and other high-end equipment key parts remanufacturing. However, the repair quality and performance of the repaired parts have been limited by the morphological and quality control problems of the process because of the formation mechanism and process of the deposition. The main reason is that the coupling of multiple process parameters makes the deposited layer morphology and surface properties difficult to be accurately predicted, which makes it difficult to regulate the process. Thus, the deposited layer forming mechanism and morphological properties of directed energy deposition were systematically analyzed, the height and width of multilayer deposition layers were taken as prediction targets, and a PSO-BP-based model for predicting the morphology of directed energy deposited layers was settled. The weights and thresholds of Back Propagation (BP) neural networks were optimized using a Particle Swarm Optimization (PSO) algorithm, the predicted values of deposited layer morphology for different process parameters were obtained, and the problem of low accuracy of deposited layer morphology prediction due to slow convergence and poor uniformity of the solution set of traditional optimization models was addressed. Remanufacturing experiments were conducted, and the experimental results showed that the deposited layer morphology prediction model proposed in this paper has a high prediction accuracy, with an average prediction error of 1.329% for the layer height and 0.442% for the layer width. The research of the paper provided an effective way to control the morphology and properties of the directed energy deposition process. A valuable contribution is made to the field of laser remanufacturing technology, and significant implications are held for various industries such as aerospace, metallurgy, and energy.

Bacteria are known to cope with amino acid starvation by halting growth and prolonging survival via the stringent response signaling system. Previous investigations have allowed us to understand how the stringent response regulates many aspects of macromolecule synthesis and catabolism, but how amino acid starvation promotes bacterial survival at the metabolic level remains largely unclear.

With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes, Bacteroides, Blautia, Lachnospiraceae NK4A136 group, and Lactobacillus, were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis, were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.

Optimal operation of a compressor station is important since it accounts for 25 % to 50 % of a company’s total operating budget. In short-term management of a compressor station, handling demand uncertainty is important yet challenging. Previous studies either require precise information about the distribution of uncertain parameters or greatly simplify the compressor model. We build a two-stage robust optimization framework of power cost minimization in a natural gas compressor station with non-identical compressors. In the first stage, decision variables are the ON/OFF state of each compressor and discharge pressure. The worst-case cost of the second stage is incorporated in the first stage. First-stage decision variables feasibility is discussed and proper feasibility cuts are also proposed for the first stage. We employ a piece-wise approximation and propose accelerate methods. Our numerical results highlight two advantages of robust approach when managing uncertainty in practical settings: (1) the feasibility of first-stage decision can be increased by up to 45 % , and (2) the worst-case cost can be reduced by up to 25 % compared with stochastic programming models. Furthermore, our numerical experiments show that the designed accelerate algorithm has time improvements of 1518.9% on average (3785.9% at maximum).

Background The reported incidence of sexually transmitted infections (STIs) in China has been increasing over the last decades, especially among drug users, which has become one of the main burdens of public health in China. This study was conducted to estimate the prevalence and associated factors of STIs among non-injecting methamphetamine (MA) users in Eastern China. Methods A cross-sectional survey was conducted among 632 MA users in Eastern China in 2017. Demographic characteristics, sexual behaviors, behaviors of MA use and sexual health knowledge were collected through questionnaire. First pass urine specimens were collected and detected for deoxyribonucleic acid (DNA) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with Nucleic Acid Amplification Technology (NAAT), while blood specimens were collected and detected for antibodies of Human immunodeficiency virus (HIV), Herpes simplex virus type-2 (HSV-2), and syphilis with enzyme-linked immune sorbent assay (ELISA). Results Among the 632 MA users, 464 (73.42%) were males, 60.92% were Conclusions This study found that the prevalence of HSV-2 and syphilis are alarming high among non-injecting MA users in Shandong Province in Eastern China. The prevention and control intervention of STIs among MA users in Shandong were needed, especially on females and MA users ≥ 35 years of age.

The effects of differentiated cells on stem cell differentiation were analyzed by co-culture using a cell-encapsulated double-layered hydrogel system. As a polymer hydrogel matrix, a water-soluble zwitterionic polymer having both 2-methacryloyloxyethyl phosphorylcholine unit and p-phenylboronic acid unit (PMBV), was complexed spontaneously with poly(vinyl alcohol) (PVA) under mild cell culture conditions. The elastic modulus of the hydrogel was controlled by changing the composition of the polymer in the solution. Mouse mesenchymal stem cells (MSCs), C3H10T1/2 cells, were encapsulated into PMBV/PVA hydrogels and cultured. In the PMBV/PVA hydrogel with a lower creep modulus (0.40 kPa), proliferation of C3H10T1/2 cells occurred, and the formation of cell aggregates was observed. On the other hand, a higher creep modulus (1.7 kPa) of the hydrogel matrix prevented cell proliferation. Culturing C3H10T1/2 cells encapsulated in PMBV/PVA hydrogel in the presence of bone morphogenetic protein-2 increased the activity of intracellular alkaline phosphatase (ALP). This indicated that C3H10T1/2 cells differentiated into mature osteoblasts. When the C3H10T1/2 cells encapsulated in the PMBV/PVA hydrogel were cultured in combination with the mature osteoblasts in the hydrogel by a closed contacting double-layered hydrogel structure, higher ALP activity was observed compared with the cells cultured separately. It was considered that the differentiation of C3H10T1/2 cells in the hydrogel layer was induced by cytokines diffused from mature osteoblasts encapsulated in another hydrogel layer. It could be concluded that the PMBV/PVA hydrogel system provides a good way to observe the effects of surrounding cells on cell function in three-dimensional culture.

Sodium thiocyanate (NaSCN) is a naturally antibacterial component in milk, but excessive consumption of thiocyanate may cause potential risks to human health. Currently available methods for the detection of thiocyanate have some disadvantages such as poor sensitivity and high price. Here, we report a robust and cost-effective method to detect NaSCN based on paper substrates deposited with

A mild and efficient transition metal-free radical difluoroarylmethylation/cyclization of unactivated alkenes toward the synthesis of quinazolinone derivatives with easily accessible α,α-difluoroarylacetic acids has been developed.

A visible-light-catalyzed difluoroacetylated spirocyclization of N-arylpropiolamides with ethyl bromodifluoroacetate as a CF2CO2Et radical precursor is described using fac-[Ir(ppy)3] as a photocatalyst.

A practical and efficient synthetic route to construct a variety of 3-arylselenenyl/3-arylthio spiro[4.5]trienones was developed using Selectfluor reagent as a mild oxidant. This reaction proceeds via a sequence of electrophilic cation addition, spirocyclization and dearomatization, then offers an approach to introduce Se/S-centered cation into the C–C triple bonds. The utility of this protocol were justified by the excellent compatibility of a wide range of functional groups, good yields and scalability under mild reaction conditions.

This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with SMN2 copy number. SMA infants treated with either nusinersen or onasemnogene abeparvovec achieved important motor milestones not observed in the untreated cohort. NF levels declined more rapidly in the nusinersen cohort as compared with the untreated cohort. Unexpectedly, those receiving onasemnogene abeparvovec monotherapy showed a significant rise in NF levels regardless of SMN2 copy number. In contrast, symptomatic SMA infants who received nusinersen, followed by onasemnogene abeparvovec within a short interval after, did not show an elevation in NF levels. While NF cannot be used as the single marker to predict outcomes, the elevated NF levels observed with onasemnogene abeparvovec and its absence in infants treated first with nusinersen may indicate a protective effect of co-therapy during a critical period of vulnerability to acute denervation., Graphical abstract, These findings show serum neurofilaments as biomarkers to monitor spinal muscular atrophy disease onset, progression, and treatment response early in life. The absence of elevated neurofilament levels in infants treated first with nusinersen may indicate a protective effect of co-therapy with nusinersen and gene therapy during a critical period.

ObjectivesThis study constructs a quantitative assessment model of the impact of the marine environment on the offensive mine-laying operational performance of unmanned underwater vehicles (UUV), and draws quantitative evaluation conclusions.MethodsFirst, the attributes of offensive mine-laying marine environment assessment are researched and the optimal model of the TOPSIS and set pair analysis (SPA) method are proposed on the basis of the combined weight of the fuzzy analytic hierarchy process (FAHP) and entropy weight method (EWM). The current situation of UUV deployment and its impact on the marine environment are then analyzed, and the risk indexes of the marine environment on the offensive mine-laying performance of UUVs are constructed with reference to the main evaluation indexes of the operational performance of traditional and unmanned offensive mine-laying. Finally, according to the existing research results on the impact of the marine environment on UUV systems, a quantitative model of the risk indicators is completed.ResultsThe feasibility of the method and model presented in this paper is verified through a simulation experiment that optimizes the marine environmental risk scheme of the determined UUV offensive mine-laying.conclusionsIt is more effective to disassemble the marine environmental risk indications in the offensive mine-laying stage, and more scientific to construct a quantitative model of marine environmental risk indications. The dynamic preference coefficient of the combined weight takes into account both the authority of decision-making and objectivity of data, and the influence of the same and opposite factors on scheme selection is considered. Finally, the feasibility of the algorithm is verified by the simulation results.

In order to solve the problem of low mechanization level of hairy vetch harvesting, a feeding device for an anti-winding hairy vetch harvester was designed. Firstly, the physical properties of hairy vetch stalk were studied. According to the mechanical properties of hairy vetch stalk, the key components of the feeding device were designed and analyzed, the structure and working principle of the feeding device were described. Secondly, the discrete element method was used to simulate and analyze the movement performance of the feeding device. On this basis, the ternary quadratic regression orthogonal rotation combination test was established with the vertical drum, the machine forward speed, and the spiral conveyor speed as the test factors and the stem loss rate as the test index. The simulation results showed that when the vertical drum was 1037.5 r/min, the machine forward speed was 2.76 m/s, the spiral conveyor speed was 348.88 r/min, and the straw loss rate was 2.38%, and the feeding device performs best at this time. Finally, the on-site performance test of the feeding device was carried out. The results showed that: all the test indicators met the requirements of the national standard; the actual cutting width was 1.66 m; the cutting stubble height was 6.41 mm; the over stubble loss rate was 0.45%; the missed cutting loss rate was 0.20%; and the stem loss rate was 3.00%, which verified the rationality of the design of the feeding device. In order to solve the problem of low mechanization level of hairy vetch, which easily becomes entangled in the working process, an anti-winding feeding device for hairy vetch harvesting was designed.

The endoplasmic reticulum (ER)–tethered, liver-enriched stress sensor CREBH is processed in response to increased energy demands or hepatic stress to release an amino-terminal fragment that functions as a transcription factor for hepatic genes encoding lipid and glucose metabolic factors. Here, we discovered that the carboxyl-terminal fragment of CREBH (CREBH-C) derived from membrane-bound, full-length CREBH was secreted as a hepatokine in response to fasting or hepatic stress. Phosphorylation of CREBH-C mediated by the kinase CaMKII was required for efficient secretion of CREBH-C through exocytosis. Lipoprotein lipase (LPL) mediates the lipolysis of circulating triglycerides for tissue uptake and is inhibited by a complex consisting of angiopoietin-like (ANGPTL) 3 and ANGPTL8. Secreted CREBH-C blocked the formation of ANGPTL3-ANGPTL8 complexes, leading to increased LPL activity in plasma and metabolic tissues in mice. CREBH-C administration promoted plasma triglyceride clearance and partitioning into peripheral tissues and mitigated hypertriglyceridemia and hepatic steatosis in mice fed a high-fat diet. Individuals with obesity had higher circulating amounts of CREBH-C than control individuals, and human CREBH loss-of-function variants were associated with dysregulated plasma triglycerides. These results identify a stress-induced, secreted protein fragment derived from CREBH that functions as a hepatokine to stimulate LPL activity and triglyceride homeostasis.

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h and then every 24 h until days 7 after reperfusion. The pathological changes in the retina were observed by H and E staining after HIOP. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was utilized to observe retinal cell apoptosis. The mRNA expression of IL1-β, TNF-α, IL-4, IL-10, δ-opioid receptor (DOR), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) in the retina was measured by quantitative real-time PCR.Results: HIOP caused structural disorders of the retina, decreased RGCs, and increased retinal cell apoptosis. At 1 and 3 days of RIRI, retinal apoptotic cells in the EA group were significantly reduced, while there was no distinct difference in the EA group compared with the HIOP group at 7 days of RIRI. Compared with that in the HIOP group, the expression of anti-inflammatory factors, DOR and TrkB was increased, and the expression of pro-inflammatory factors was decreased in the EA group. In contrast, HIOP had no appreciable effect on BDNF expression.Conclusion: EA at Jingming (BL1) and Shuigou (GV26) or at Jingming (BL1) and Hegu (LI4) may inhibit RIRI induced inflammation through activating the DOR-BDNF/TrkB pathway to protect the retina, especially the pair of Jingming (BL1) and Shuigou (GV26) has better inhibitory effects on inflammation.