•It is an integrated inventory model for supply chains considering carbon emissions.•Carbon emissions from production, transportation, and storage are all considered.•Carbon taxation, limited carbon ...emissions, and cap and trade are considered.•The optimal number of shipments, transportation lot size are determined.•The optimal amount of investment in green technologies are also determined.
This study investigates the effects that carbon policies and green technologies may have on the integrated inventory of a two-echelon supply chain with consideration of carbon emissions during the processes of product production, transportation, and storage. The three carbon emissions policies: limited total carbon emissions, carbon taxation, and cap-and-trade, are considered in the study. The proposed model can assist firms in determining their corresponding optimal production quantity, delivery quantity, and green investment amount with an aim of minimizing the costs under different carbon emissions policies. Moreover, this study also provides practical implications for the government to make appropriate policies and regulations in balancing the trade-off between environmental protection and economic growth. Finally, the results indicate that firms adopting the carbon tax policy would prefer to invest in a relatively efficient green technology. With regard to the sources of carbon emissions, the effects of unit carbon emissions during production and unit distance of transportation are the most dramatic, and the cap limit has greater effects than the carbon emissions reduction factor of the green technology. Besides, the government should set the limit of carbon emissions within a reasonable range under the cap-and-trade policy to avoid suppliers overly trading their quotas of carbon emissions.
Summary
Bone marrow‐derived mesenchymal stem cells (BMMSCs) exhibit degenerative changes, including imbalanced differentiation and reduced proliferation during aging, that contribute to age‐related ...bone loss. We demonstrate here that autophagy is significantly reduced in aged BMMSCs compared with young BMMSCs. The autophagy inhibitor 3‐methyladenine (3‐MA) could turn young BMMSCs into a relatively aged state by reducing their osteogenic differentiation and proliferation capacity and enhancing their adipogenic differentiation capacity. Accordingly, the autophagy activator rapamycin could restore the biological properties of aged BMMSCs by increasing osteogenic differentiation and proliferation capacity and decreasing adipogenic differentiation capacity. Possible underlying mechanisms were explored, and the analysis revealed that autophagy could affect reactive oxygen species and p53 levels, thus regulating biological properties of BMMSCs. In an in vivo study, we found that activation of autophagy restored bone loss in aged mice. In conclusion, our results suggest that autophagy plays a pivotal role in the aging of BMMSCs, and activation of autophagy could partially reverse this aging and may represent a potential therapeutic avenue to clinically treat age‐related bone loss.
•ED nurses exposed to COVID-19 could be psychologically and mentally exhausted.•Prevalence of depression among 1,103 ED nurses was 43.61% (95% CI=40.68%–46.54%).•A heightened awareness of and timely ...treatment for depression for frontline ED nurses should be provided.
Frontline medical staff exposed to the novel coronavirus disease (COVID-19) could be psychologically and mentally exhausted. This study examined the prevalence of depressive symptoms (depression hereafter) and their correlates and the association between depression and quality of life (QOL) in Emergency Department (ED) nurses during the COVID-19 pandemic in China.
This national, cross-sectional online survey was conducted between March 15 and March 20, 2020 in China. Depression and QOL were measured using the 9-item Patient Health Questionnaire, and the World Health Organization Quality of Life Questionnaire-Brief Version, respectively.
The overall prevalence of depression in 1103 ED nurses was 43.61% (95% CI=40.68–46.54%). Multiple logistic regression analysis revealed that working in tertiary hospitals (OR=1.647, P=0.009), direct patient care of COVID-19 patients (OR=1.421, P=0.018), and current smokers (OR=3.843, P<0.001) were significantly associated with depression. After controlling for covariates, nurses with depression had an overall lower QOL compared to those without (F(1,1103)=423.83, P<0.001).
Depression was common among ED nurses during the COVID-19 pandemic. Considering the negative impact of depression on quality of patient care and nurses’ QOL, a heightened awareness of, and early treatment for depression for frontline ED nurses should be provided.
Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID‐19). A total of 101 severe and ...critical patients with coronavirus SARS‐CoV‐2 infection were enrolled in this open, case‐control, multicenter, prospective study. According to the patients’ and their families’ willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28‐day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre‐treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin‐6 (IL‐6) level. The serum IL‐6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL‐6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28‐day follow‐up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28‐day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID‐19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short‐term mortality.
The artificial liver blood purification treatment blocks cytokine storm by clearing inflammatory mediators such as IL‐6, thus preventing severe cases from progressing to critically ill stage and remarkably reducing the short‐term mortality.
Myocardial hypoxia is a major cause of cardiac dysfunction due to its triggering cell injury and apoptosis. Deregulated microRNAs and their roles in cardiomyocyte apoptosis have attracted much ...attention. miR-133a is among the most abundant of the miRNAs present in the normal heart, and significant changes in expression of miR-133a were observed in response to anoxia stress. However, the role of this microRNA in myocardial hypoxia-induced apoptosis is presently unclear. In this study, we identified that miR-133a expression was down-regulated in hypoxic H9c2 cells, and its expression gradually decreased with hypoxia time. Functional analysis revealed that miR-133a attenuated hypoxia-induced apoptosis. We further detected expression of apoptosis-related proteins. The results showed that miR-133a suppressed the expression of apoptotic proteins caspase-8, caspase-9, and caspase-3 significantly, while improved the expression of Bcl-2. Bioinformatics analysis, combined with dual-luciferase reporter analysis, was applied to determine that miR-133a directly was binded to the 3′-untranslated region (3′-UTR) of TAGLN2 mRNA and suppressed expression at both transcriptional and translational levels. Next, TAGLN2 knockout was used to reveal that TAGLN2 modulated hypoxia-induced apoptosis via caspase-8 apoptotic pathway. Taken together, our data demonstrated the roles of miR-133a in hypoxia-induced apoptotic and implicate its potential in cardiac dysfunctions therapy.
•Intercropping drove higher grain N and total N accumulation, NTE, and NUE.•Interspecies interaction upregulated GS/GOGAT activity and gene expression in leaves.•GS/GOGAT stimulated by intercropping ...linked with higher straw and total N accumulation.•Upregulated GS/GOGAT after wheat heading stages contributed to higher NTE and NUE.
Glutamine synthetase (GS) and the glutamate synthase (GOGAT) cycle are closely related to plant nitrogen (N) uptake, translocation, and remobilization, but little attention has been paid to their role in intercropping systems. A two-factor field trial involving two planting patterns (mono-cropped wheat MW and wheat intercropped with faba bean) and four N levels (N0, N1, N2, and N3 with respective application rates of 0, 90, 180, and 270 kg ha−1 for wheat) were studied. Nitrogen accumulation and allocation were determined, and the GS and GOGAT activities and their gene expression in the leaves were analyzed. The results showed that wheat total aboveground N accumulation and grain N accumulation were increased when wheat was intercropped with faba bean. Intercropped wheat (IW) presented higher N translocation efficiency (NTE) than MW (except for the N3 level during 2018–2019) during the reproductive growth stage. Thus, the grain yield (except for the N3 level), N harvest index (NHI), and apparent N recovery rate (ANR) were higher in IW than in MW. In addition, total GS, Fd-GOGAT, and NADH-GOGAT activities in the wheat leaves were increased by 27 %–42 %, 17 %–44 %, and 15 %–25 %, respectively, under the N0, N1, and N2 levels from the stem elongation to filling stages when wheat was intercropped with faba bean. On average, GS1, GS2, Fd-GOGAT, and NADH-GOGAT gene expression in the IW flag leaves was 1.4–4.3 times, 1.2–3.6 times, 1.2–2.2 times, and 1.4–6.7 times higher, respectively, than that in MW. Both GS and GOGAT activity and gene expression were tightly related to straw N accumulation and NTE rather than grain N accumulation based on simple correlation analysis. In addition, wheat total N accumulation at maturity was more sensitive to GS and GOGAT activity and gene expression in the flag leaves during the heading, flowering, and filling stages, and ANR only linked with GS and GOGAT activity at the filling stage. Hence, it could be concluded that up-regulated GS and GOGAT activity and gene expression induced by intercropping during the reproductive growth stages contributed to higher NTE and NUE in intercropping. These findings suggest that interspecies interactions modulated GS and GOGAT, which play a crucial role in the intercropping advantage and provide insight into the mechanism of enhanced NUE under intercropping.
Background
Angiogenesis alteration in tooth support tissue plays an essential role in periodontitis. Mesenchymal stem cells (MSCs) can affect vessel formation by endothelial cells (ECs) through ...paracrine function. Autophagy is reported to be closely related to cell secretion. Here we investigated the angiogenesis‐promoting ability of MSCs that reside in the periodontal ligament (known as periodontal ligament stem cells, PDLSCs) under inflammatory conditions in order to explore the mechanism of angiogenesis alteration in periodontitis.
Methods
PDLSCs were isolated from healthy and inflamed human periodontal ligament tissues (HPDLSCs and PPDLSCs, respectively). HPDLSCs were subjected to an inflammatory environment (IPDLSCs) in vitro using inflammatory cytokines. Angiogenesis‐promoting cytokine expression and autophagy were evaluated in PDLSCs by quantitative reverse transcription‐polymerase chain reaction and western‐blot analysis before co‐culturing them with ECs. The angiogenesis ability of ECs in the co‐culture system was examined by a matrigel tube formation test. Rapamycin and pcDNA for Beclin‐1 (cDNA‐Beclin‐1) were used to promote autophagy in PDLSCs and siRNA Beclin‐1 (siBeclin‐1) was used to repress it.
Results
The inflammatory environment increased autophagy and the expression of basic fibroblast growth factor (bFGF) and angiogenin (Ang) in PDLSCs. More tube formation was observed in ECs from the co‐culture system which was pretreated with tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β. PDLSCs treated with rapamycin or transfected with cDNA‐Beclin‐1 showed higher expression levels of bFGF and Ang that promoted tube formation by the co‐cultured ECs. PDLSCs transfected with siBeclin‐1 resulted in the opposite results.
Conclusion
Autophagy modulates angiogenesis‐promoting ability of PDLSCs, which could be increased by an inflammatory environment.
The exploitation of specific guests which can respond to external stimuli is the main approach for the construction of stimuli‐responsive supramolecular polymers (SPs) based on host–guest ...interactions. Most functional guests, however, fail to manifest stimuli‐responses. Herein, a hypoxia‐responsive dimeric azocalixarene (D‐SAC4A) with outstanding hosting properties was used as the macrocyclic building block for the preparation of host stimuli‐responsive SPs. Since azocalixarenes can also be compatible with stimuli‐responsive guests, an antitumor drug, camptothecin (CPT), was chosen and linked via a disulfide‐containing linker to afford a glutathione (GSH)‐responsive ditropic guest (D‐CPT). A unique dual‐responsive SP was obtained by 1 : 1 mixing of D‐SAC4A and D‐CPT in water, which further assembled into SP nanoparticles (DSPNs). DSPNs displayed outstanding stability against dilution and biological interferants, as well as precise CPT‐release under GSH and hypoxia conditions. In vitro and in vivo experiments demonstrated the good biosafety and tumor‐suppressive effects of DSPNs.
A host–guest dual‐response supramolecular polymer was prepared based on a dimeric hypoxia‐responsive azocalixrene and GSH‐cleavable CPT dimer (D‐CPT), which further self‐assembles into nanoparticles and exhibits excellent antitumor therapy performance.
Genome-scale CRISPR-Cas9 screening technology is a powerful tool to systematically identify genes essential for cancer cell survival. Herein, TKOv3, a genome-scale CRISPR-Cas9 knock-out library, was ...screened in the gastric cancer (GC) cells, and relevant validation experiments were performed. We obtained 854 essential genes for the AGS cell line, and 184 were novel essential genes. After knocking down essential genes: SPC25, DHX37, ABCE1, SNRPB, TOP3A, RUVBL1, CIT, TACC3 and MTBP, cell viability and proliferation were significantly decreased. Then, we analysed the detected essential genes at different time points and proved more characteristic genes might appear with the extension of selection. After progressive selection using a series of open datasets, 41 essential genes were identified as potential drug targets. Among them, methyltransferase 1 (METTL1) was over expressed in GC tissues. High METTL1 expression was associated with poor prognosis among 3 of 6 GC cohorts. Furthermore, GC cells growth was significantly inhibited after the down-regulation of METTL1 in vitro and in vivo. Function analysis revealed that METTL1 might play a role in the cell cycle through AKT/STAT3 pathways. In conclusion, compared with existing genome-scale screenings, we obtained 184 novel essential genes. Among them, METTL1 was validated as a potential therapeutic target of GC.
PDF
