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ABSTRACTUnder the ‘ Cap-and-Trade’ mechanism of carbon emission, the low carbon management of supply chain is an indispensable link in the process of enterprise emission reduction. Constrained by carbon price and consumers’ environmental awareness, this paper establishes a two-stage game model between retailers and manufacturers under decentralized and centralized decisions. Under the decentralized decision, this paper analyzes the optimal carbon emissions before and after the transfer, the conditions of transfer and the changes of profits with the proportion of transfer. Under the centralized decision, Nash equilibrium is used to study the distribution of additional profits. Conclusions are obtained as follows. (a) There are thresholds for carbon price and consumers’ environmental awareness on carbon emissions, and the optimal emissions on both sides of the threshold will vary with the cost of emission reduction. (b) In a decentralized decision, the participation of retailers in abatement depends on the market abatement costs and abatement benefits, while a certain range of transfer rates can optimize the profitability of retailers. (c) In the centralized decision, manufacturer and retailer formulate emission reduction strategies jointly and share the extra profits equally.

Abstract Background Anti‐PD‐1/PD‐L1 therapeutics have been widely used in the clinic in various tumors, including advanced esophageal cancer, showing remarkable treatment efficacy. Factors determining the response to anti‐PD‐1/PD‐L1 therapeutics are numerous, including the tumor microenvironment, such as CD8+ T cells and expression of PD‐1/PD‐L1. Our study aimed to explore the effect of chemoimmunotherapy on the expression of CD8+ T cells, TIM‐3, and FOXP3+ in tumor, paratumor tissues, and the expression of PD‐L1, IDO, in tumor, paratumor tissues, and lymph nodes, and analyze the correlation among these markers. Methods A total of 18 patients were allocated into two treatment groups: a treatment group and a concurrent control group. A total of 38 tissue samples, 114 slides (tumor, paratumor, and lymph node) were collected in the treatment group, and 37 tissue samples, 111 slides (tumor, paratumor, and lymph node) were collected in the concurrent control group. Results The expression of PD‐L1, CD8+, FOXP3+, TIM‐3, and IDO in tumors, paratumor tissues, but not lymph nodes, was significantly affected by chemoimmunotherapy. Compared with patients without chemoimmunotherapy, the expression of CD8+ T cells, IDO, and PD‐L1 was significantly decreased in tumor and paratumor tissues after chemoimmunotherapy, while FOXP3+ expression was significantly decreased only in tumor tissues, and TIM‐3 expression was significantly decreased only in paratumor tissues. Moreover, the correlation between these markers was also completely altered after chemoimmunotherapy. In addition, N staging was associated with high expression of CD8 in advanced esophageal squamous cell carcinoma in the concurrent control group. Conclusion This study provides new insight into the effects of CI treatment on isolated CD8+ T cell infiltration, PD‐L1, IDO, FOXP3+ and TIM‐3 expression as well as their cross‐talk in different tissues enabling a better understanding of the impact of CI treatment on the immune microenvironment.

Abstract Robust ex vivo expansion of NK-92 cells is essential for clinical immunotherapy. The vitamin B group is critical for the expansion and function of immune cells. This study optimized a vitamin combination by response surface methodology based on an in-house designed chemically defined serum-free medium EM. The serum-free medium EM-V4 with an optimal vitamin combination favoured ex vivo expansion of NK-92 cells. The characteristics of glucose metabolism of NK-92 cells in EM-V4 and the relationships between cell expansion and metabolism were investigated. NK-92 cells in EM-V4 underwent metabolic reprogramming. An elevated ratio of glucose-6-phosphate dehydrogenase/phosphofructokinase (G6PDH/PFK) indicated that NK-92 cells shifted towards the pentose phosphate pathway (PPP). An increase in the ratio of pyruvate dehydrogenase/lactate dehydrogenase (PDH/LDH) suggested that the cells shifted towards the Krebs (TCA) cycle, i.e., from glycolysis to aerobic metabolism. The enhanced ratio of oxygen consumption rate/extracellular acidification rate (OCR/ECAR) indicated that NK-92 cells were more reliant on mitochondrial respiration than on glycolysis. This shift provided more intermediate metabolites and energy for biosynthesis. Thus, EM-V4 accelerated biomass accumulation and energy production to promote NK-92 cell expansion by regulating the metabolic distribution. Our results provide valuable insight for the large-scale ex vivo expansion of clinically available NK-92 cells. Graphical Abstract

Abstract The application of natural killer (NK) cells as potential antitumor effector cells appears to be valuable for immunotherapies. However, the clinical use of NK cells is limited because the technical difficulties associated with mass production NK cells at sufficiently high numbers represents a great challenge. Ex vivo expansion of NK cells is a key technology for cell therapy. Bioreactor systems can generate homogeneous culture condition and modulate the environmental and biochemical cues. In this study, a novel magnetically controlled bioreactor was developed for supporting NK cells ex vivo expansion. Using synthetic magnetic beads, the stirring device of the magnetically controlled bioreactor generated reduced shearing force. The intermittent magnetic field was applied for magnetic beads movement to homogenize the culture system. NK-92 cells were cultured in the magnetically controlled bioreactor and the expansion and function of expanded cells were investigated on day 8. The results showed that the expansion of NK-92 cells in the bioreactor was 67.71 ± 10.60-fold, which was significantly higher than that of the T25 culture flask (P

Abstract Epigallocatechin-3-gallate (EGCG) is a plant-derived flavonoid compound with the ability to promote the differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts. However, the effect of EGCG on the osteogenic differentiation of the human umbilical cord-derived mesenchymal stem cells (HUMSCs) is rarely studied. Therefore, in this study, the osteogenic effects of EGCG are studied in the HUMSCs by detecting cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition and the expression of relevant osteogenic markers. The results showed that EGCG can promote the proliferation and osteogenic differentiation of the HUMSCs in vitro at a concentration of 2.5–5.0 μM. Unfortunately, the EGCG is easily metabolized by cells during cell culture, which reduces its bioavailability. Therefore, in this paper, EGCG-loaded microspheres (ECM) were prepared and embedded in chitosan/carboxymethyl cellulose/montmorillonite (CS/CMC/MMT) scaffolds to form CS/CMC/MMT-ECM scaffolds for improving the bioavailability of EGCG. The HUMSCs were cultured on CS/CMC/MMT-ECM scaffolds to induce osteogenic differentiation. The results showed that the CS/CMC/MMT-ECM scaffold continuously released EGCG for up to 22 days. In addition, CS/CMC/MMT-ECM scaffolds can promote osteoblast differentiation. Taken together, the present study suggested that entrainment of ECM into CS/CMC/MMT scaffolds was a prospective scheme for promotion osteogenic differentiation of the HUMSCs. Graphical Abstract

Abstract Effective nutrient transport and appropriate mechanical stimulation play important roles in production of tissue-engineered bone grafts. In this study, an experimental set-up for magnetic-driven dynamic culture of cells was designed to mimic the microenvironment of the bone tissue. Here, its ability to contribute to osteogenic differentiation was investigated by inoculating human umbilical cord mesenchymal stem cells (HUMSCs) on magnetic scaffolds. The cytocompatibility of the developed magnetic scaffolds was verified for HUMSCs. Magnetic scaffolds seeded with HUMSCs were exposed to magnetic fields. The results showed that magnetic fields did not affect cell activity and promoted HUMSCs osteogenic differentiation. The magnetic scaffolds were magnetically driven for dynamic culture in the experimental set-up to evaluate the influence of HUMSCs osteoblast differentiation. The results indicated that magnetic-driven dynamic culture increased cell alkaline phosphatase (ALP) activity (p

Abstract Background Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.

Abstract The FGF/MEK/ERK and Wnt/β-catenin signaling pathways have previously been proved to regulate mouse embryonic stem cell (mESCs) function. However, the relationships between these two pathways, especially their different functions on proliferation and pluripotency of mESCs, were rarely mentioned. Here, we investigated the effects of FGF/MEK/ERK and Wnt/β-catenin pathway regulators and their combinations on the proliferation and pluripotency of mESCs under serum- and feeder-free conditions. We found that MEK inhibitor PD0325901 and FGFR inhibitor SU5402 has paradoxical function on mESCs; one could promote proliferation along with differentiation and the other one could improve pluripotency while impairing cell proliferation. The combination of these two kinds of inhibitors could better regulate FGF/MEK/ERK pathway. Wnt/β-catenin pathway regulators SB216763 led to differentiation while promoting proliferation of mESCs. When we used FGF/MEK/ERK and Wnt/β-catenin pathway regulators in combination, the total expansion fold of mESCs reached 318.78 ± 47.95 and the proportion of SSEA-1-positive cells reached 82.40 ± 2.74% which were significantly higher than using the regulators alone. This finding indicates that regulators of FGF/MEK/ERK and Wnt/β-catenin pathways play different roles in the regulatory networks of mESCs. Their combination can better maintain the undifferentiated state and promote the proliferation of mESCs under serum- and feeder-free conditions.

Abstract Background Unlike conventional cultivation systems, liquid mixing in floating photobioreactors (PBRs) is solely induced by their hydrodynamic movement in response to waves, and this movement is affected by the wave conditions (wave height and wave period), the PBR configuration and the culture depth. However, to the best of our knowledge, a practical study of the hydrodynamic movements of PBRs has not been previously conducted. Results This study aims to investigate the hydrodynamic performance of floating PBRs in response to wave conditions. First, the effects of the experimental wave height (2–10 cm) and wave period (0.8–1.8 s) on movement was investigated using two 1.0 m2 PBR models: a square PBR (1.0 m/1.0 m; length/width) and a rectangular PBR (1.7 m/0.6 m). The results indicated that wave movement became not only more intense with increasing wave height, but also less intense when the wave period decreased. However, the square PBR experienced more intense movement than the rectangular PBR, but also little mooring force. The effects of culture depth (0.5, 1.0 and 2.0 cm) were investigated and the results showed that the culture depth significantly affected the hydrodynamic movements of the PBRs; however, the mooring forces were unaffected. Finally, the movement and mooring-line forces of PBRs equipped with different mooring systems were investigated. The use of two different mooring systems had little effect on PBR movement; however, a mooring system with floaters was able to significantly reduce the mooring line forces compared to a system without floaters. During this study, the greatest force (10.5 N) was found for the rectangular PBR using a mooring system without floaters, whereas the lowest force (0.67 N) was observed for a rectangular PBR using a mooring system with floaters. Conclusions These studies have provided basic data describing the fluid dynamics of floating PBRs; as well as their structural design and scale up. These results also provide guidance for the selection of ocean fields with suitable wave conditions; as well as a proper mooring methods to ensure safe operation.

Objective. To compare the effects of continuous paravertebral block analgesia and patient-controlled intravenous analgesia after minimally invasive radical esophagectomy for esophageal cancer and their effects on postoperative recovery. Methods. A retrospective analysis was performed among 233 patients who underwent minimally invasive esophageal cancer radical operation and met the requirements, including 87 patients (group C) who were successfully placed with a continuous paravertebral block device under direct vision and 146 patients (group P) who used a patient-controlled intravenous analgesia device. Visual analogue pain score (VAS) at rest and in motion for 1, 3, 6, 12, 24, 36, and 48 hours after awakening, incidence of adverse reactions of the two analgesic methods, occurrence of pulmonary complications after operation, use of emergency analgesics, and hospital stay after operation was recorded. Results. The VAS scores of group C in resting and active state at 1, 3, 6, 12, 24, 36, and 48 hours after operation were significantly lower than those of group P (P

Abstract The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) plays essential roles in embryogenesis and carcinogenesis. IGF2BP1 serves as a post-transcriptional fine-tuner regulating the expression of some essential mRNA targets required for the control of tumor cell proliferation and growth, invasion, and chemo-resistance, associating with a poor overall survival and metastasis in various types of human cancers. Therefore, IGF2BP1 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. Nevertheless, a few studies have also demonstrated its tumor-suppressive role. However, the details about the contradictory functions of IGF2BP1 are unclear. The growing numbers of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified as its direct regulators, during tumor cell proliferation, growth, and invasion in multiple cancers. Thus, the mechanisms of post-transcriptional modulation of gene expression mediated by IGF2BP1, miRNAs, and lncRNAs in determining the fate of the development of tissues and organs, as well as tumorigenesis, need to be elucidated. In this review, we summarized the tissue distribution, expression, and roles of IGF2BP1 in embryogenesis and tumorigenesis, and focused on modulation of the interconnectivity between IGF2BP1 and its targeted mRNAs or non-coding RNAs (ncRNAs). The potential use of inhibitors of IGF2BP1 and its related pathways in cancer therapy was also discussed.

Objective: Lung cancer is the leading cause of cancer‑related death worldwide with a relatively low 5‑year relative survival rate of 16%. Novel and efficient therapeutic approach for lung cancer is desperately needed. Materials and Methods: Targeting cancer stem cells (CSCs) provides a promising strategy to eradicate malignancies. The Notch signaling pathway plays an important role in the control of cell fates and developmental processes including CSCs. The function of Notch1 in the regulation of CSCs and whether targeting Notch1 could be a potential therapy for lung cancer were explored in this study. Lung CSCs (LCSCs) were isolated from A549 cells and identified as CD44+/CD24– cells by magnetic‑assisted cell sorting, then the putative LCSCs were treated with Notch1 inhibitor and Notch1 small interfering RNAs (siRNAs); the growth and proliferation of LCSCs were investigated to test the effect of Notch1 blocking on the growth and viability of LCSCs. Results: CD44+/CD24– cells isolated from A549 cells possessed stem cell‑like properties with high expression of Notch1. Blocking Notch1 by inhibitor DAPT or siRNA both inhibited the growth capacity of LCSCs. Conclusion: Our discovery demonstrated a depression of growth in CD44+/CD24– and A549 cells caused by blockade of Notch signaling pathway. Further studies are needed to demonstrate the detailed effects of Notch1 blocking on the LCSCs. Nevertheless, targeting the Notch pathway has exhibited great potential to be an improved lung cancer treatment. [ABSTRACT FROM AUTHOR]

Hydrogenated amorphous carbon nitride (a-C:N:H) films are prepared with C[H.sub.3]CN dielectric barrier discharges (DBD) plasmas and the effects of varying the C[H.sub.3]CN pressure (p) and the frequency of the power supply (f) on the films growth and film properties are analyzed. The studies have shown that p and f have influenced the structures, compositions, deposition rates, surface roughness and nanohardness of deposited a-C:N:H films.

Long non-coding RNAs (IncRNAs) are known to be potential factors in promoting tumor progression. However, the function and mechanism of IncRNA XIST in non-small cell lung cancer (NSCLC) remains poorly understood. The expression levels of IncRNA XIST in NSCLC tissues and cell lines were detected with real-time PCR, and the correlation of the expression level of XIST with histopathological characteristics and prognosis was analyzed. The biological function of IncRNA XIST was validated through assays in vivo and in vitro. The expression of IncRNA XIST was significantly up-regulated in NSCLC tissues. In addition, overexpression of XIST was positively correlated with the advanced clinical status of tumors, as well as poor overall survival and DFS. A tumor suppressive effect was presented via functional knockdown of IncRNA XIST. Up-regulation of XIST enhanced the proliferation, migration, and invasion ability of NSCLC cells both in vivo and in vitro. Mechanically, it was indicated that XIST could serve as an endogenous competitive RNA modulating miR-744, leading to the miR-744/RING1 signaling pathway inhibition and Wnt/β-catenin signaling pathway activation. Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: TNF-related apoptosis-inducing ligand (TRAIL) functions as a soluble cytokine and has been demonstrated significant antitumor activity against a variety of cancer cell lines without toxicity to most normal cells. Cisplatin is a potent anticancer agent and is widely used in the clinical for treatment of human cancers. Adeno-associated virus (AAV2) is a promising gene delivery vehicle for its advantage of low pathogenicity and long-term gene expression. However, lack of tissue specificity caused low efficiency of AAV transfer to target cells. The promoter of human telomerase reverse transcriptase (hTERT) is a good candidate to enhance targeting efficiency of AAV in cancer cells. Although AAV-mediated TRAIL controlled by hTERT promoter (AAV-hTERT-TRAIL) has obvious antitumor activity, the tumor cannot be completely eradicated. In this study, we first examined the effectiveness of combination therapy of cisplatin and AAV-hTERT-TRAIL on human hepatocellular carcinoma (HCC) in vitro and in vivo. Methods: For in vitro experiments, tumor cell lines were treated with cisplatin, virus, or both. The transgene TRAIL expression controlled by hTERT promoter was evaluated in BEL7404 HCC cell line. Cytotoxicity was performed by MTT analysis. Cell apoptosis was detected by flow cytometry analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and AAV-hTERT-TRAIL was assessed in human hepatocellular carcinoma xenografts mouse model. Results: The enhanced TRAIL expression was observed in BEL7404 cells treated with AAV-hTERT-TRAIL plus cisplatin. Treatment with both AAV-hTERT-TRAIL and cisplatin exhibited stronger cytotoxicity and induced more significant apoptosis in cancer cells compared with AAV-hTERT-TRAIL or cisplatin alone, respectively. Moreover, in animal experiments, the combined treatment greatly suppressed tumor growth and resulted in tumor cell death. Conclusions: AAV-mediated therapeutic gene expression in combination with chemotherapy provides a promising therapeutic strategy for human cancers. These data suggest that combined use of AAV-hTERT-TRAIL and cisplatin may have potential clinical application. [ABSTRACT FROM AUTHOR]

The hematopoietic reconstitution of cord blood (CB) CD34+ cells grown in static and stirred system was studied. Static cultures were better than stirred cultures for cell expansion. Engraftment of stirred-culture hematopoietic stem cells (HSCs) was higher than static-culture HSCs. Stirred-culture HSCs had better multilineage reconstitution ability and colony-forming ability than static-culture HSCs. Static cultures thus favor the expansion of HSCs and stirred cultures are more effective in preserving functional HSCs. [ABSTRACT FROM AUTHOR]

Ex vivo expanded CD34+ hematopoietic stem and progenitor cells (HSPCs) have compromised homing and engraftment capacities. To investigate underlying mechanisms for functional changes of expanded HSPCs, we compared gene expression profiling of cultured and fresh CD34+ cells derived from cord blood using SMART-PCR and cDNA array: 20 genes were up-regulated while 25 genes were down-regulated in cultured CD34+ HSPCs. These differentially expressed genes are involved primarily in proliferation, differentiation, apoptosis, and homing. [ABSTRACT FROM AUTHOR]