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This paper focuses on the ways COVID-19 has facilitated the development of platform-based supply chains. Platform-based supply chains are of great research value as a new direction for supply chain development, especially in China. The first part of the paper summarizes the characteristics of the COVID-19 era around the world, the second part points out the situation of platform-based supply chains in China, and the third part analyses the promotion effect of the epidemic. As platform-based supply chains are still at an emerging stage, there are very few analyses and theoretical studies on their operation models, and for this reason this paper lacks empirical data.

It is well known that organic acids (OAs) could affect the flavour of fruit juices and beverages. However, the molecular mechanism of aroma release is still unclear. In this study, the effects of citric acid (CA), L-(-)-malic acid (MA) and L-lactic acid (LA) on the release of six selected esters and their sensory perception were investigated by means of HS-GC-MS analyses and odour detection threshold determination, respectively. Meanwhile, the density functional theory (DFT) calculation was employed to explore the interaction modes between esters and OAs. HS-GC-MS analyses showed that the concentration and the type of OAs regulated the release of esters. The results were basically consistent with the detection threshold change of those esters. The DFT calculation suggested that the main intermolecular interaction was hydrogen bonds, and several esters could form a ternary ring structure with OAs through hydrogen bonds. The interactions can induce the different release behaviours of esters in OAs water solution. The number of carboxyl functional groups in OAs and the spatial conformation of esters appeared to influence the magnitude of the interaction. The above results demonstrated the mechanism of OAs affecting the release of esters and indicated a possible flavour control way by using different OAs and OA concentrations.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). , the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

As a crucial lymphocyte subset, γδT cells exhibit tumoricidal properties without the constraint of major histocompatibility complex restriction. In recent years, the in vitro expansion of human peripheral blood-derived γδT cells has emerged as a promising candidate for adoptive immune cell therapy (ACT). However, given the limitations in accessing and sourcing human peripheral blood, it remains challenging to expand γδT cells to the magnitude required for clinical cancer immunotherapy. Therefore, the objective of this study was to establish an innovative approach for the in vitro differentiation of γδT cells from human embryonic stem cells (hESCs). In present study, by simulating the in vivo developmental process of γδT cells, we established stroma cell-free differentiation approach with three stages under 3D suspension culture in conjunction with using hypoxic conditions. Under our protocol, around 39% of CD34 + CD31 + hematopoietic endothelial cells were induced in cell spheroids at first stage under hypoxic conditions, and over 99% of suspended/floating cells from cell spheroids were early CD43 + hematopoietic progenitor cells (HPCs), and over 90% of CD45 + HPCs were produced at the second stage, demonstrating the homogeneity of cell population and its high hematopoietic potential. Eventually over 40% of mature CD45 + CD3 + TCRγδ + T cells were generated at the final stage, and these γδT cells exerted cytotoxicity against hepatoma cancer cells and simultaneously significantly inhibited their proliferation. RNA sequencing analysis revealed that the differentiation process of hESC-derived γδT cells was transcriptomically similar to those of in vivo courses. Therefore, our findings ultimately offer a novel technique to address the challenge of sourcing γδT cells for ACT therapies.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Forsythiaside A, a phenylethanoid glycoside monomer extracted from Forsythia suspensa, shows anti-inflammatory, anti-infective, anti-oxidative, and antiviral pharmacological effects. The precise mechanism underlying the antiviral action of forsythiaside A is not completely clear. Therefore, in this study, we aimed to determine whether the anti-influenza action of forsythiaside A occurs via the retinoic acid-inducible gene-I–like receptors (RLRs) signaling pathway in the lung immune cells. Forsythiaside A was used to treat C57BL/6J mice and MAVS−/− mice infected with mouse-adapted influenza A virus FM1 (H1N1, A/FM1/1/47 strain), and the physical parameters (body weight and lung index) and the expression of key factors in the RLRs/NF-κB signaling pathway were evaluated. At the same time, the level of virus replication and the ratio of Th1/Th2 and Th17/Treg of T cell subsets were measured. Compared with the untreated group, the weight loss in the forsythiaside A group in the C57BL/6J mice decreased, and the histopathological sections showed less inflammatory damage after the infection with the influenza A virus FM1 strain. The gene and protein expression of retinoic acid-inducible gene-I (RIG-I), MAVS, and NF-κB were significantly decreased in the forsythiaside A group. Flow cytometry showed that Th1/Th2 and Th17/Treg differentiated into Th2 cells and Treg cells, respectively, after treatment with forsythiaside A. In conclusion, forsythiaside A reduces the inflammatory response caused by influenza A virus FM1 strain in mouse lungs by affecting the RLRs signaling pathway in the mouse lung immune cells.

Background Exosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. Results In vitro, PKH26 labeled-hESC-Exosomes were shown to be internalized and integrated into TGFβ-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labeled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFβRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFβRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFβRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. Conclusions Our results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFβRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR-6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p. Graphical Abstract

BackgroundSeveral previous studies have shown that the development of depression is often accompanied by chronic diseases; although closely related, the mechanism between them is not clear. Here we investigate the potential role of functional limitations, social interaction, and life satisfaction in the relationship between chronic diseases and depressive symptoms in middle-aged and older adults in China.MethodsWe selected 2407 respondents aged ≥45 from the China Health and Retirement Longitudinal Study conducted in 2013, 2015, and 2018. We established panel data to estimate the longitudinal impact of chronic diseases on depressive symptoms and the mediating role of functional limitations, social interaction, and life satisfaction.ResultsChronic diseases were associated with more depressive symptoms. All of the mediating pathways examined passed functional limitations, and approximately 43.4% of the association between chronic diseases and depressive symptoms was explained by these three mediating variables.ConclusionsThe impact of chronic diseases on depressive symptoms was primarily mediated by functional limitations, and the mediating role of social interaction and life satisfaction was also confirmed. Therefore, attention should be paid to reducing the level of functional limitation in middle-aged and older adults with chronic diseases and improving life satisfaction by increasing social opportunities to alleviate depressive symptoms in middle-aged and older adults.

Background Nursing students encounter various stressors during their clinical practicum; however, the stressors are not the same during different periods. At present, studies on the stressors and coping styles of nursing students in the middle period of their clinical practicum are rare. Aims The current study aimed to explore the stressors and coping styles of nursing students in the middle period of their clinical practicum. Methods A qualitative study with a descriptive phenomenological method was conducted to collect data from 10 nursing students undergoing the middle period of their clinical practicum from December 2020 to February 2021. The data were collected by semistructured interviews using interview outlines prepared in advance. The data were analyzed by Colaizzi’s analysis method. Results The stressors experienced by nursing students in the middle period of their clinical practicum mainly included personal reasons, teaching arrangements, interpersonal relationships, occupational particularity and career planning. Additionally, nursing students coped with the stressors that they face in the clinical practicum by eliminating stressors and regulating emotions. Conclusions Nursing students experienced various stressors and used a variety of coping styles in the middle period of their clinical practicum, which was different from what occurred in the early and late periods. Targeted interventions should be formulated and implemented to relieve nursing students’ stress and guide them to adopt effective coping styles.

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9 + basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9 + BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9 + BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9 + BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.