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Increasing customer apprehensions regarding the security and nutritional value of agricultural goods are compelling governments and industries to implement traceable, transparent, and reputable logistics management systems. Blockchain-based agricultural logistics management systems guarantee the permanence of data once it is uploaded but cannot cope with the risk of data being falsified before uploading to the blockchain. In this work, we developed a collaborative game model between government bodies and agricultural enterprises based on the evolutionary game theory and explored the influencing factors of enterprises following the rules to share the real traceability information through numerical simulation using MATLAB. The findings show that government incentives and penalties promote positive behavior, and consumer and media supervision contribute to supply chain transparency, but firms tend to share truthful information only when it benefits them. This study builds upon existing research on the impact of social variables on both members' decision-making behavior. It highlights the positive roles of consumers and the media in the supervision of agricultural product traceability, which can help to raise public awareness of social responsibility and thus promote positive interaction in the market.

Abstract Background Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. Methods Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. Results We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. Conclusion These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Abstract With the rapid spread of the novel coronavirus (COVID-19), a sustained global pandemic has emerged. Globally, the cumulative death toll is in the millions. The rising number of COVID-19 infections and deaths has severely impacted the lives of people worldwide, healthcare systems, and economic development. We conducted a retrospective analysis of the characteristics of COVID-19 patients. This analysis includes clinical features upon initial hospital admission, relevant laboratory test results, and imaging findings. We aimed to identify risk factors for severe illness and to construct a predictive model for assessing the risk of severe COVID-19. We collected and analyzed electronic medical records of confirmed COVID-19 patients admitted to the Affiliated Hospital of Jiangsu University (Zhenjiang, China) between December 18, 2022, and February 28, 2023. According to the WHO diagnostic criteria for the novel coronavirus, we divided the patients into two groups: severe and non-severe, and compared their clinical, laboratory, and imaging data. Logistic regression analysis, the least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis were used to identify the relevant risk factors for severe COVID-19 patients. Patients were divided into a training cohort and a validation cohort. A nomogram model was constructed using the “rms” package in R software. Among the 346 patients, the severe group exhibited significantly higher respiratory rates, breathlessness, altered consciousness, neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) levels compared to the non-severe group. Imaging findings indicated that the severe group had a higher proportion of bilateral pulmonary inflammation and ground-glass opacities compared to the non-severe group. NLR and LDH were identified as independent risk factors for severe patients. The diagnostic performance was maximized when NLR, respiratory rate (RR), and LDH were combined. Based on the statistical analysis results, we developed a COVID-19 severity risk prediction model. The total score is calculated by adding up the scores for each of the twelve independent variables. By mapping the total score to the lowest scale, we can estimate the risk of COVID-19 severity. In addition, the calibration plots and DCA analysis showed that the nomogram had better discrimination power for predicting the severity of COVID-19. Our results showed that the development and validation of the predictive nomogram had good predictive value for severe COVID-19.

Abstract Complex coumarins (CCs) represent characteristic metabolites found in Apiaceae plants, possessing significant medical value. Their essential functional role is likely as protectants against pathogens and regulators responding to environmental stimuli. Utilizing genomes and transcriptomes from 34 Apiaceae plants, including our recently sequenced Peucedanum praeruptorum, we conduct comprehensive phylogenetic analyses to reconstruct the detailed evolutionary process of the CC biosynthetic pathway in Apiaceae. Our results show that three key enzymes – p-coumaroyl CoA 2’-hydroxylase (C2’H), C-prenyltransferase (C-PT), and cyclase – originated successively at different evolutionary nodes within Apiaceae through various means of gene duplications: ectopic and tandem duplications. Neofunctionalization endows these enzymes with novel functions necessary for CC biosynthesis, thus completing the pathway. Candidate genes are cloned for heterologous expression and subjected to in vitro enzymatic assays to test our hypothesis regarding the origins of the key enzymes, and the results precisely validate our evolutionary inferences. Among the three enzymes, C-PTs are likely the primary determinant of the structural diversity of CCs (linear/angular), due to divergent activities evolved to target different positions (C-6 or C-8) of umbelliferone. A key amino acid variation (Ala161/Thr161) is identified and proven to play a crucial role in the alteration of enzymatic activity, possibly resulting in distinct binding forms between enzymes and substrates, thereby leading to different products. In conclusion, this study provides a detailed trajectory for the establishment and evolution of the CC biosynthetic pathway in Apiaceae. It explains why only a portion, not all, of Apiaceae plants can produce CCs and reveals the mechanisms of CC structural diversity among different Apiaceae plants.

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

"Research Findings:" Although the importance of block play to children's spatial ability has been recognized globally, little is known about children's use of spatial frames of reference during spatial processing. This study investigated the intervention with guided block play to promote children's use of their intrinsic frame of reference, an identified effective frame of reference for spatial information. Participants included 42 kindergarten children (M[subscript age]=67.12 months, SD = 3.91, 48% girls) and 42 pre-kindergarten children (M[subscript age]=55.80 months, SD = 3.63, 57% girls) from one public kindergarten in Shanghai, China. A quasi-experiment method was used with a four-month intervention program designed for the experiment groups. Statistically significant differences were identified in the performance of the spatial tasks between the experiment and control groups in both kindergarten and pre-kindergarten children after the intervention. The results revealed that block-play interventions can effectively increase children's ability to use their intrinsic frame of reference and their preference in using this frame for spatial representations. "Practice or Policy:" These findings provided a new perspective on analyzing children's spatial competence and supported the benefits of block play interventions with empirical evidence.

"Research Findings:" Pattern creation (PC) is creating a pattern unit based on children's own understanding of the concept of pattern, without being provided with a pattern unit as a reference, and the repetition of this pattern unit to create a complete structure. This study explored the performance and predictors of pattern creation (PC) among Chinese preschoolers at five to six years of age. Altogether 48 children (Mage = 5.44 years, SD = 0.38, 56% girls) from one public kindergarten in Shanghai participated in two experiments designed to test individual PC abilities and cognitive and mathematical skills. The results indicated that: (1) 5 to 6-year-old Chinese preschoolers could create basic patterns of different types (single linear patterns, multiple linear patterns, and circular patterns) and different levels (one-dimensional Pattern, multi-dimensional Pattern, and no Pattern) with various self-designed patterning strategies (e.g., unit extraction, one-to-one appearance matching, counting elements with different colors and shapes, and self-talking); (2) visual working memory and series relations in reasoning ability were significantly related to children's PC performance, among which the visual working memory served as a unique predictor of children's overall PC competence. "Practice or Policy:" These findings provided empirical evidence and a profound understanding of young children's PC competence and patterning strategies and highlighted the impact of visual working memory and series relations on PC in early learning.

Objective: The extraction process of alkali-extracted abalone viscera polysaccharides (Aavp) was optimized, and the preventive and repair effects of purified Aavp on H2O2 oxidative damage on L929 cells were studied to provide a reference for the development and application of Aavps. Methods: Crude Aavp was obtained by hot alkali extraction followed by alcohol precipitation, and its extraction process was optimized by the response surface method. The preventive and repair abilities of H2O2 oxidative damage on L929 cells were analyzed. Resulst: The optimum extraction conditions of crude Aavps were as follows: Solid-liquid ratio of 1:150 g/mL, extraction time of 2 h, and extraction temperature of 70 ℃. Under these optimal conditions, the yield of crude Aavp was 8.57%. In the prevention test of H2O2 oxidative damage on L929 cells, different doses of purified Aavp (20, 50 and 100 μg/mL) had a significant preventive effect on L929 cell oxidative damage (P

Abstract To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48–86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.

Natural killer (NK) cells are cytotoxic immune cells that can eliminate target cells without prior stimulation. Human induced pluripotent stem cells (iPSCs) provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers. In this in vitro study, a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells, and distinct maturational stages of iPSC-NK were characterized. Mature cells of CD56bright CD16bright phenotype showed upregulation of CD56, CD16, and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure, while exposure to aggressive atypical teratoid/rhabdoid tumor (ATRT) cell lines enhanced NKG2D and NKp46 expression. Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γ secretion in activated NK cells. CD56bright CD16bright iPSC-NK cells showed a ratio-dependent killing of ATRT cells, and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT. The iPSC-NK cells were also cytotoxic against other brain, kidney, and lung cancer cell lines. Further NK maturation yielded CD56−ve CD16bright cells, which lacked activation markers even after exposure to interleukins or ATRT cells - indicating diminished cytotoxicity. Generation and characterization of different NK phenotypes from iPSCs, coupled with their promising anti-tumor activity against ATRT in vitro, offer valuable insights into potential immunotherapeutic strategies for brain tumors.

Abstract To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6–48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Abstract This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18–83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24–28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (β = 0.67, 95% CI 0.35–0.98, P

Abstract Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2–13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.

Background: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults. Methods: The study was based on data collected from the 1999–2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors. Results: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80–0.94, P

IntroductionEndoglucanase (EG) and cellobiohydrolase (CBH) which produced by microorganisms, have been widely used in industrial applications.MethodsIn order to construct recombinant bacteria that produce high activity EG and CBH, in this study, eg (endoglucanase) and cbh (cellobiohydrolase) were cloned from the rumen microbial genome of yak and subsequently expressed independently and co-expressed within Lactococcus lactis NZ9000 (L. lactis NZ9000).ResultsThe recombinant strains L. lactis NZ9000/pMG36e-usp45-cbh (L. lactis-cbh), L. lactis NZ9000/pMG36e-usp45-eg (L. lactis-eg), and L. lactis NZ9000/pMG36e-usp45-eg-usp45-cbh (L. lactis-eg-cbh) were successfully constructed and demonstrated the ability to secrete EG, CBH, and EG-CBH. The sodium carboxymethyl cellulose activity of the recombinant enzyme EG was the highest, and the regenerated amorphous cellulose (RAC) was the specific substrate of the recombinant enzyme CBH, and EG-CBH. The optimum reaction temperature of the recombinant enzyme CBH was 60°C, while the recombinant enzymes EG and EG-CBH were tolerant to higher temperatures (80°C). The optimum reaction pH of EG, CBH, and EG-CBH was 6.0. Mn2+, Fe2+, Cu2+, and Co2+ could promote the activity of CBH. Similarly, Fe2+, Ba2+, and higher concentrations of Ca2+, Cu2+, and Co2+ could promote the activity of EG-CBH. The addition of engineered strains to whole-plant corn silage improved the nutritional quality of the feed, with the lowest pH, acid detergent fiber (ADF), and neutral detergent fiber (NDF) contents observed in silage from the L. lactis-eg group (p

Convolutional neural networks (CNNs) play a prominent role in solving problems in various domains such as pattern recognition, image tasks, and natural language processing. In recent years, neural architecture search (NAS), which is the automatic design of neural network architectures as an optimization algorithm, has become a popular method to design CNN architectures against some requirements associated with the network function. However, many NAS algorithms are characterised by a complex search space which can negatively affect the efficiency of the search process. In other words, the representation of the neural network architecture and thus the encoding of the resulting search space plays a fundamental role in the designed CNN performance. In this paper, to make the search process more effective, we propose a novel compact representation of the search space by identifying network blocks as elementary units. The study in this paper focuses on a popular CNN called DenseNet. To perform the NAS, we use an ad-hoc implementation of the particle swarm optimization indicated as PSO-CNN. In addition, to reduce size of the final model, we propose a segmentation method to cut the blocks. We also transfer the final model to different datasets, thus demonstrating that our proposed algorithm has good transferable performance. The proposed PSO-CNN is compared with 11 state-of-the-art algorithms on CIFAR10 and CIFAR100. Numerical results show the competitiveness of our proposed algorithm in the aspect of accuracy and the number of parameters.

Abstract Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

In this paper, we study eight single-machine scheduling problems with rejection and position-dependent parameters. We consider two position-dependent parameters as follows: (1) position-dependent weights and (2) position-dependent processing times. In addition, we also introduce a weight-modifying activity or a rate-modifying activity into our problems. In the first six problems, the task is to minimize the sum of the total weighted completion time of accepted jobs and the total rejection cost of rejected jobs. We show that all six problems can be solved in polynomial time. In the last two problems, the task is to minimize the total weighted completion time of accepted jobs under the constraint that the total rejection cost of rejected jobs can not exceed a given upper bound. We show that these two problems are binary NP-hard and each problem admits an FPTAS.

Objective: Alkali-extracted polysaccharides from Abalone viscera (Aavp) were isolated and purified. The structure and antioxidant activity of Aavp were studied, which would provide a reference for developing and applying polysaccharides. Methods: The crude alkali-extracted polysaccharide was prepared by hot alkali extraction and alcohol precipitation. After the purification of DEAE sepharose fast flow and sephacryl S-400 HR, the purified polysaccharide was obtained and subjected to the structural analysis and antioxidant activity assay, such as Gas chromatography (GC), high-performance liquid chromatography (HPLC), infrared spectroscopy (IR), and thermogravimetric analyzer (TGA), etc. Result: Four kinds of components (Aavp Ia, Aavp Ib, Aavp IIa, and Aavp IIb) were obtained from the crude polysaccharide. Because of the highest yield, Aavp IIa was selected for further structural analysis. Aavp IIa was composed of xylose and galactose, with a relative molecular weight of 166513 Da. IR characterized the α-glycosidic bond configuration. The composition of Aavp IIa was possible as follows: The molar percentage of the galactose 1→4 glycosidic bond was 11.81%, the galactose 1→3 glycosidic bond was 34.14%, and the galactose 1→2 glycosidic bond was 10.14%. The molar percentage of the xylose 1→3 glycosidic bond was 33.85%, and the 1→2 and 1→4 glycosidic bond was 10.06%. Thermogravimetric analysis showed that Aavp IIa was broken and decomposed at 226.4~332.6 °C, and the thermal weight loss rate was 43.65%. Antioxidant experiments showed that Aavp IIa had a scavenging rate of 85.89% for superoxide anion radicals and 62.17% for DPPH radicals, respectively, presenting a certain antioxidant activity. Conclusion: Aavp is a heteropolysaccharide with specific antioxidant activity.