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The objective of this study was to assess the differences in the quality of fried potato fries across various potato varieties (lines) in Qinghai Province, as well as to identify suitable potato varieties (lines) for the production of fried potato fries. Twenty-one representative potato varieties (lines) were selected as raw materials for the production of fried potato fries, and then their fundamental nutritional attributes and quality characteristics were evaluated. The suitability of the fried potato fries was assessed using principal component analysis, correlation analysis, and iterative clustering. The results revealed considerable differences in the nutritional indicators among different potato varieties (lines) in Qinghai Province. Principal component analysis identified five principal components, which accounted for 86.43% of the cumulative variance contribution rate. Leveraging the comprehensive scores from iterative clustering, three suitable potato varieties (lines) for processing fried potato fries were identified, namely, Qingshu 15, Qingshu 14, and Qing 11-2-9. Evaluation of their palatability characteristics demonstrated that the fried potato fries exhibited a crispy exterior and tender interior texture (sensory score of 62~73), favorable chewiness (52~53), and bright color (a* value of 4.0~6.5), aligning with practical applications. The results achieved efficient utilization of potato processing in Qinghai Province, which could meet consumer demand, and provided a theoretical basis for potato quality improvement and special variety breeding.

Abstract With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, ‘Xusuan No. 6’ was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Abstract Sustainable multi-story building designs are gaining increasing attention in light of the green development of the building industry. Recently, many studies have been conducted to determine the optimized embodied energy considering size of structural members and materials strength using a single objective function. In this context, the current study adopted a multi-objective function based on cost and Embodied Energy (EE) for the sustainable design of the entire multi-story building. A BuildingEnergy computer program is used to assess the energy consumption performance of a multi-story reinforcement cement concrete building. Based on the proposed method, an analysis is carried out to compare the optimal solutions for multi-story building. Furthermore, a detailed parametric study was conducted to explore the main factors for energy-efficient column and beam design. The results revealed that with a comparison of the most “carbon-friendly” and “cost-friendly” solutions, an added cost of 6–7% can contribute up to a 13% emission reduction. The sectional dimensions, steel rebar, concrete strengths, cost ratio, building height, and eccentricity remarkably influence sustainable design, cost optimization, and minimum carbon emission. Overall, this study could help to define cost-effective and energy-efficient structural members. Eventually, the EE is confirmed to be a feasible parameter for designing more sustainable multi-story RCC buildings.

Asphalt pavement is widely applied to the surface in high-grade highway tunnels due to its prominent preponderance in road performance. However, asphalt is flammable as the binder material to adhere the aggregates and other additives, resulting that a fire in the semi-closed space of the tunnel can ignite and burn asphalt pavement to generate a large amount of heat and smoke. Therefore, further promoting the advance of flame-retardant asphalt pavement is essential to ensure security in tunnels. We gathered the relevant standards or regulations of diverse nations and test methods concerning flame retardancy of asphalt. Then we reviewed the research status of flame-retardant asphalt mixture, including thermal characteristics of the asphalt and four fractions, the flame retardants applicable to asphalt, and effects on other components. This review demonstrated that establishing universal standards and test methods is a research basis specifically for flame-retardant asphalt pavement. To optimize the flame retardancy of asphalt pavement, it should focus on the synergy with diversified aspects such as asphalt binders, multiple flame retardants, aggregates, mineral powders, fibers, and other additives.

Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.

To improve wear resistance and corrosion behavior of TC4 alloy, plasma electrolytic oxidation (PEO) was performed in a TiC particle containing electrolyte. Results show that increasing PEO current density is conducive to improving the coating thickness, promoting incorporation of TiC particles, and enhancing wear resistance of the coating. While increasing TiC content in electrolyte reduces PEO coating thickness. Under the optimized condition, where the electrolyte has 2 g L−1 TiC and PEO current density is 5 A dm−2, the derived PEO coating exhibits both high wear resistance and corrosion resistance. Moreover, it is shown that the incorporated TiC particles are more likely to become components in the inner layer of the derived MAO coating.

Abstract Liver fibrosis, as a consequence of chronic liver disease, involves the activation of hepatic stellate cell (HSC) caused by various chronic liver injuries. Emerging evidence suggests that activation of HSC during an inflammatory state can lead to abnormal accumulation of extracellular matrix (ECM). Investigating novel strategies to inhibit HSC activation and proliferation holds significant importance for the treatment of liver fibrosis. As a member of the doublecortin domain-containing family, doublecortin domain containing 2 (DCDC2) mutations can lead to neonatal sclerosing cholangitis, but its involvement in liver fibrosis remains unclear. Therefore, this study aims to elucidate the role of DCDC2 in liver fibrosis. Our findings revealed a reduction in DCDC2 expression in both human fibrotic liver tissues and carbon tetrachloride (CCl4)-induced mouse liver fibrotic tissues. Furthermore, exposure to transforming growth factor beta-1(TGF-β1) stimulation resulted in a dose- and time-dependent decrease in DCDC2 expression. The overexpression of DCDC2 inhibited the expression of α-smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1α1), and reduced the activation of HSC stimulated with TGF-β1. Additionally, we provided evidence that the Wnt/β-catenin signaling pathway was involved in this process, wherein DCDC2 was observed to inhibit β-catenin activation, thereby preventing its nuclear translocation. Furthermore, our findings demonstrated that DCDC2 could attenuate the proliferation and epithelial-mesenchymal transition (EMT)-like processes of HSC. In vivo, exogenous DCDC2 could ameliorate CCl4-induced liver fibrosis. In summary, DCDC2 was remarkably downregulated in liver fibrotic tissues of both humans and mice, as well as in TGF-β1-activated HSC. DCDC2 inhibited the activation of HSC induced by TGF-β1 in vitro and fibrogenic changes in vivo, suggesting that it is a promising therapeutic target for liver fibrosis and warrants further investigation in clinical practice.

Abstract Background Multisystem childhood Langerhans cell histiocytosis (LCH) patients, especially those with risk organ (RO) involved, had not been satisfactorily treated under the international traditional schemes as high incidences of reactivation with late sequelae were largely reported. Over years, we have observed that LCH patients with varied clinical symptoms responded differently to different drugs, suggesting the current grouping strategies based only on the number of organs involved might be inadequate. LCH has been defined as an inflammatory myeloid tumor, thus this study has innovatively divided LCH pediatric patients into inflammatory or malignant symptoms group, and given different intensity treatment regimens to different groups. Aim This clinical study aimed to explore a more appropriate patient grouping system according to the LCH symptom presentations and examine the clinical outcomes of treatment strategies in different groups. Methods According to the clinical manifestations, 37 cases of children were divided into Group A (only inflammatory symptoms) and Group B (malignant symptoms with or without inflammatory symptoms). Patients in Group A and B were initially treated with vindesine (VDS) and methylprednisolone (PSL), and VDS, PSL, pirarubicin (THP) and cyclophosphamide (CTX), respectively. Treatment responses were evaluated six weeks after the induction therapy in all patients, and the criteria were disease status and clinical scores of symptoms. Results Pre- and post-treatment scores were 1.22 ± 0.547 and 0.00 ± 0.00 in Group A, and 14.79 ± 1.686 and 1.00 ± 1.563 in Group B, respectively. All patients had subsequentlly received maintenance therapy without progressive disease. The 4-year overall survival (OS) rate was 100% in both groups and the 4-year event-free survival (EFS) was 94.4% in Group A and 89.5% in Group B, respectively. There were no obvious adverse events (AE) in Group A, whereas the main AE in Group B were alopecia and non-lethal hematological toxicity. Conclusion Stratification according to patients’ clinical symptoms, with low-intensity treatment for inflammatory symptoms (mild manifestations) and intensive treatment with multiple drugs for malignant symptoms (severe manifestations), is a positive exploration that simplifies stratification method, achieves good long-term remission of the disease, and obtains a higher survival rate and quality of life, which seemed to be more appropriate for LCH patients.

Abstract Acute lung injury (ALI) is an acute and progressive hypoxic respiratory failure that could progress to acute respiratory distress syndrome (ARDS) with a high mortality rate, thus immediate medical attention and supportive care are necessary. The pathophysiology of ALI is characterized by the disruption of the alveolar-capillary barrier and activation of neutrophils, leading to lung tissue damage. The receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising target for the treatment of multiple inflammatory diseases, but the role of RIPK1 in the ALI remains poorly understood. In this study, we aimed to figure out the pathological role of RIPK1 in ALI, especially in the pulmonary immune microenvironment involving neutrophils and endothelial cells. In vivo experiments showed that RIPK1 inhibitor protected against lipopolysaccharide (LPS)-induced lung injury in mouse models, with reduced neutrophils and monocytes infiltration in the lungs. Further studies demonstrated that, besides the inhibitory action on necroptosis, RIPK1 inhibitor directly suppressed reactive oxygen species (ROS) generation and inflammatory cytokines secretion from neutrophils. Furthermore, RIPK1 inhibition maintains the barrier function in TNF-α-primed vascular endothelial cells and prevents their activation induced by the supernatant from LPS-stimulated neutrophils. Mechanistically, the aforementioned effects of RIPK1 inhibitor are associated with the NF-κB signaling pathway, which is partially independent of necroptosis inhibition. These results provide new evidence that RIPK1 inhibitor directly regulates the function of neutrophils and endothelial cells, as well as interferes with the interactions between these two cell types, therefore contributing to a better understanding of RIPK1 in ALI and providing a potential avenue for future therapeutic interventions.

Abstract Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

Abstract Low computational efficiency and non-linearity behaviour make the simulation of the overall building structure problematic to attain with a single dynamic or static method. Thus, this paper uses a plastic deformation (PD) method based on concrete plasticity theory (CPT) for comparative analysis of multi-storey reinforcement cement concrete (RCC) and composite buildings under common and rare earthquake loads. For this purpose, a 15-storey tall building was selected for analysis using ABAQUS software. At first, a possible building model was created and then plastic deformation analysis was performed using the new PD method under both common and rare earthquakes. After that, a nonlinear time history analysis was conducted, and the results of plastic strain distribution, lateral displacement, peak acceleration, storey stiffness, shear force, storey drift, normalised shear, and top deflection of the RCC and composite buildings were studied deeply. The fundamental time period of the RCC model was found to be 5.2 s while the fundamental time period of the composite model was 6 s. Under common and rare earthquake leads, the peak acceleration of the RCC building was 19% and 22% higher than composite buildings, respectively. Under common and rare seismic loads, the top deflections of the composite building were 33% and 36% higher than those of RCC buildings, respectively. In the case of the RCC building, it was found in this study that higher peak acceleration (PA) of the ground motion led to higher storey top displacement, storey drift, shear force and top deflection under both ground motions. Numerical results suggested that the use of composite structure is more durable than RCC structure. It was also concluded that the PD method could also be effectively used for the analysis of RCC and composite buildings under dynamic loads.

Abstract Background There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment. Methods To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models. Results Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation. Conclusions Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.

Abstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.