CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia.

BACKGROUND: Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells. METHODS: Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK). RESULTS: Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20-, Jurkat: CD19-CD20-) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed. CONCLUSIONS: The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.

Room-Temperature Synthesis of a COFs Membrane Via LBL Self-Assembly Strategy for Energy Harvesting.

The covalent organic frameworks (COFs) membrane with ordered and confined one-dimensional channel has been considered as a promising material to harvest the salinity gradient energy from the seawater and river water. However, the application of the COFs in the field of energy conversion still faces the challenges in membrane preparation. Herein, energy harvesting is achieved by taking advantage of a COFs membrane where TpDB-HPAN is synthesized via layer-by-layer self-assembly strategy at room temperature. The carboxy-rich TpDB COFs can be expediently assembled onto the substrate with an environmental-friendly method. The increased open-circuit voltage (Voc ) endows TpDB-HPAN membrane with a remarkable energy harvesting performance. More importantly, the application perspective is also illuminated by the cascade system. With the advantages of green synthesis, the TpDB-HPAN membrane can be considered as a low-cost and promising candidate for energy conversion.

Expression of 5-HT Relates to Stem Cell Marker LGR5 in Patients with Gastritis and Gastric Cancer.

BACKGROUND: 5-Hydroxytryptamine (5-HT) and stem cells marker G-protein-coupled receptor 5 (LGR5) are associate with gastrointestinal inflammation and tumorigenesis. But the relationship between 5-HT and LGR5 is unclear. OBJECTIVE: To explore the expression and correlation of 5-HT and LGR5 in gastric mucosa of patients with gastritis and gastric cancer (GC). METHODS: A total of 41 patients with GC and 98 patients with chronic gastritis were included in this study. The expression of TPH1 mRNA, LGR5 mRNA and ß-catenin mRNA in gastric mucosa were explored by Real-time Quantitative polymerase chain reaction (qPCR). 5-HT-positive cells and LGR5-positive cells in gastric mucosa were detected by immunohistochemistry stains. The co-localization of 5-HT and chromogranin A (CgA), 5-HT receptor4 (5-HTR4) and LGR5 were detected by multiplex immunofluorescence. RESULTS: The expression of 5-HT and LGR5 in patients with GC was significantly higher than patients with chronic gastritis (p < 0.05). The positive rate of 5-HT and LGR5 increased sequentially in the patients with non-atrophic gastritis, intestinal metaplasia and GC, which were 18.52%, 35.56% and 75.61% for 5-HT, and 27.78%, 40.91% and 95.12% for LGR5, respectively. The expression of 5-HT and LGR5 was positively correlated in gastritis and GC patients (p < 0.05). Moreover, the expression level of TPH1 mRNA and LGR5 mRNA was also positively correlated in gastritis patients (r = 0.7377, p < 0.001). Besides, 5-HT was partially co-localized with CgA, and 5-HTR4 was co-localized with LGR5 in gastric mucosa. CONCLUSION: The increase of 5-HT synthesis in gastric mucosa may have an impact on LGR5-positive gastric epithelial stem cells.

Catalyzing Benzoxazine Polymerization with Titanium-Containing POSS to Reduce the Curing Temperature and Improve Thermal Stability.

Trisilanolphenyl-polyhedral oligomeric silsesquioxane titanium (Ti-Ph-POSS) was synthesized through the corner-capping reaction, and Ti-Ph-POSS was dispersed in benzoxazine (BZ) to prepare Ti-Ph-POSS/PBZ composite materials. Ti-Ph-POSS could catalyze the ring-opening polymerization (ROP) of BZ and reduce the curing temperature of benzoxazine. In addition, Ti immobilized on the Ti-Ph-POSS cage could form covalent bonds with the N or O atoms on polybenzoxazine, improving the thermal stability of PBZ. The catalytic activity of the Ti-Ph-POSS/BZ mixtures was assessed and identified through 1H nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared (FTIR) analyses, while thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA) were used to determine the thermal properties of the composite. It was found that PBZ exhibited a higher glass transition temperature (Tg) and better thermal stability when Ti-Ph-POSS was added. The curing behavior of the Ti-Ph-POSS/BZ mixtures showed that the initial (Ti) and peak (Tp) curing temperatures sharply decreased as the content of Ti-Ph-POSS and the heating rate increased. The curing kinetics of these Ti-Ph-POSS/BZ systems were analyzed using the Kissinger method, and the morphology of Ti-Ph-POSS/PBZ was determined via scanning electron microscopy (SEM). It was found that the Ti-Ph-POSS particles were well distributed in the composites. When the content exceeded 2 wt%, several Ti-Ph-POSS particles could not react with benzoxazine and were only dispersed within the PBZ matrix, resulting in aggregation of the Ti-Ph-POSS molecules.

Large-Area Covalent Organic Polymers Membrane via Sol-Gel Approach for Harvesting the Salinity Gradient Energy.

Many materials with nanofluidic channels are exploited to achieve salinity gradient energy conversion. However, most materials are fragile, difficult to process, or only prepared into a limited size, which greatly restricts their practical application in the future. Herein, a covalent organic polymers membrane with high mechanical property and stability is fabricated, which can keep integrity in harsh conditions for up to 1 month. In addition, by using the sol-gel approach, a large-area membrane with an area of 26 × 26 cm is expediently fabricated in lab conditions. When the membrane is applied to salinity gradient energy conversion, the maximum output power density is up to 6.21 W m-2 . This work provides a simple method for the fabrication of large-area membrane for salinity gradient energy conversion in future real-world applications.

Brain Wave-Like Signal Modulator by Ionic Nanochannel Rectifier Bridges.

Smart modulation of bioelectric signals is of great significance for the development of brain-computer interfaces, bio-computers, and other technologies. The regulation and transmission of bioelectrical signals are realized through the synergistic action of various ion channels in organisms. The bionic nanochannels, which have similar physiological working environment and ion rectification as their biological counterparts, can be used to construct ion rectifier bridges to modulate the bioelectric signals. Here, the artificial smart ionic rectifier bridge with light response is constructed by anodic aluminum oxide (AAO)/poly (spiropyran acrylate) (PSP) nanochannels. The output ion current of the rectifier bridge can be switched between "ON" and "OFF" states by irradiation with UV and visible (Vis) light, and the conversion efficiency (η) of the system in "ON" state is ≈70.5%. The controllable modulation of brain wave-like signal can be realized by ionic rectifier bridge. The ion transport properties and processes of ion rectifier bridges are explained using theoretical calculations based on Poisson-Nernst-Planck (PNP) equations. These findings have significant implications for the understanding of the intelligent ionic circuit and combination of artificial smart ionic channels to organisms, which provide new avenues for development of intelligent ion devices.

Generating Road Networks for Old Downtown Areas Based on Crowd-Sourced Vehicle Trajectories.

With the popularity of portable positioning devices, crowd-sourced trajectory data have attracted widespread attention, and led to many research breakthroughs in the field of road network extraction. However, it is still a challenging task to detect the road networks of old downtown areas with complex network layouts from high noise, low frequency, and uneven distribution trajectories. Therefore, this paper focuses on the old downtown area and provides a novel intersection-first approach to generate road networks based on low quality, crowd-sourced vehicle trajectories. For intersection detection, virtual representative points with distance constraints are detected, and the clustering by fast search and find of density peaks (CFDP) algorithm is introduced to overcome low frequency features of trajectories, and improve the positioning accuracy of intersections. For link extraction, an identification strategy based on the Delaunay triangulation network is developed to quickly filter out false links between large-scale intersections. In order to alleviate the curse of sparse and uneven data distribution, an adaptive link-fitting scheme, considering feature differences, is further designed to derive link centerlines. The experiment results show that the method proposed in this paper preforms remarkably better in both intersection detection and road network generation for old downtown areas.

MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease.

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.

Elucidating the Role and Regulation of a Lactate Permease as Lactate Transporter in Bacillus coagulans DSM1.

A key feature of Bacillus coagulans is its ability to produce l-lactate via homofermentative metabolism. A putative lactate permease-encoding gene (lutP) and the gene encoding its regulator (lutR) were identified in one operon in B. coagulans strains. LutP orthologs are highly conserved and located adjacent to the gene cluster related to lactate utilization in most lactate-utilizing microorganisms. However, no lactate utilization genes were found adjacent to lutP in all sequenced B. coagulans strains. The stand-alone presence of lutP in l-lactate producers indicates that it may have functions in lactate production. In this study, B. coagulans DSM1 was used as a representative strain, and the critical roles of LutP and its regulation were described. Transport property assays showed that LutP was essential for lactate uptake. Its regulator LutR directly interacted with the lutP-lutR intergenic region, and lutP transcription was activated by l-lactate via regulation by LutR. A biolayer interferometry assay further confirmed that LutR bound to an 11-bp inverted repeat in the intergenic region, and lutP transcription began when the binding of LutR to the lutP upstream sequence was inhibited. We conclusively showed that lutP encodes a functional lactate permease in B. coagulansIMPORTANCE Lactate-utilizing strains require lactate permease (LutP) to transport lactate into cells. Bacillus coagulans LutP is a previously uncharacterized lactate permease with no lactate utilization genes situated either adjacent to or remotely from it. In this study, an active lactate permease in an l-lactate producer, B. coagulans DSM1, was identified. Lactate supplementation regulated the expression of lactate permease. This study presents physiological evidence of the presence of a lactate transporter in B. coagulans Our findings indicate a potential target for the engineering of strains in order to improve their fermentation characteristics.

Spoilage of refrigerated Litopenaeus vannamei: eavesdropping on Acinetobacter acyl-homoserine lactones promotes the spoilage potential of Shewanella baltica.

Shewanella baltica and Acinetobacter are among the predominant spoilage bacteria in refrigerated shrimp (Litopenaeus vannamei). S. baltica are incapable of producing acyl-homoserine lactone (AHL) quorum sensing signals, but can respond to environmental AHLs. In this paper, Acinetobacter was found to produce three AHLs, i.e. N-butanoyl-l-homoserine lactone (C4-HSL), N-(3-oxohexanoyl)-l-homoserine lactone (O-C6-HSL) and N-(3-oxooctanoyl)-l-homoserine lactone (O-C8-HSL), according to thin-layer chromatography using the bioreporter Agrobacterium tumefaciens A136. The agar diffusion and ß-galactosidase assays revealed that S. baltica could eavesdrop on these three AHLs from Acinetobacter. Eavesdropping on Acinetobacter AHLs especially C4-HSL was found to boost the growth of S. baltica particularly under nutrient limiting conditions (up to 40-fold increase) in the co-culture experiments. The azocasein assay revealed that S. baltica produced fourfold more extracellular proteases in response to Acinetobacter AHLs. As demonstrated by the biofilm crystal violet staining assay and confocal laser scanning microscopy, eavesdropping also decreased the biofilm-forming capacity of Acinetobacter. By inoculation of S. baltica and Acinetobacter onto surface-sterilized shrimp, eavesdropping was found to endow a growth advantage to S. baltica in vivo, resulting in a 0.5 day shortened shelf life of shrimp according to total volatile basic nitrogen levels and sensory analysis. Overall, the AHL-dependent eavesdropping increased the spoilage potential of S. baltica, providing a fresh perspective on the spoilage process of refrigerated L. vannamei, and this may inspire the development of novel preservation techniques in the future to further reduce post-harvest loss of shrimp.

Non-sterilized fermentation of high optically pure D-lactic acid by a genetically modified thermophilic Bacillus coagulans strain.

BACKGROUND: Optically pure D-lactic acid (≥ 99%) is an important precursor of polylactic acid. However, there are relatively few studies on D-lactic acid fermentation compared with the extensive investigation of L-lactic acid production. Most lactic acid producers are mesophilic organisms. Optically pure D-lactic acid produced at high temperature not only could reduce the costs of sterilization but also could inhibit the growth of other bacteria, such as L-lactic acid producers. RESULTS: Thermophilic Bacillus coagulans is an excellent producer of L-lactic acid with capable of growing at 50 °C. In our previous study, the roles of two L-lactic acid dehydrogenases have been demonstrated in B. coagulans DSM1. In this study, the function of another annotated possible L-lactate dehydrogenase gene (ldhL3) was verified to be leucine dehydrogenase with an activity of 0.16 units (µmol/min) per mg protein. Furthermore, the activity of native D-lactate dehydrogenase was too low to support efficient D-lactic acid production, even under the control of strong promoter. Finally, an engineered B. coagulans D-DSM1 strain with the capacity for efficient production of D-lactic acid was constructed by deletion of two L-lactate dehydrogenases genes (ldhL1 and ldhL2) and insertion of the D-lactate dehydrogenase gene (LdldhD) from Lactobacillus delbrueckii subsp. bulgaricus DSM 20081 at the position of ldhL1. CONCLUSIONS: This genetically engineered strain produced only D-lactic acid under non-sterilized condition, and finally 145 g/L of D-lactic acid was produced with an optical purity of 99.9% and a high yield of 0.98 g/g. This is the highest optically pure D-lactic acid titer produced by a thermophilic strain.

The potential application of strategic released apigenin from polymeric carrier in pulmonary fibrosis.

AIM: The capability of reducing fibrotic and inflammatory responses in lung tissues represents a gold standard for evaluating the efficacy of therapeutic interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of therapeutic strategies have been employed in clinic to treat PF, but limited success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this study, we explore the potential therapeutic effect of apigenin in lung fibrosis. MATERIALS AND METHODS: Apigenin was employed to treat IPF in a bleomycin-induced PF rat model. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle, NP) to improve its bio-solubility and bio-availability. The properties (e.g. size, apigenin loading and release profile) of the apigenin loaded polymer carrier were well-characterized. In vitro study was performed to assess the impact of apigenin on pulmonary cell viability, growth, as well as inflammatory and pro-fibrosis responses in pulmonary cells. The impact of apigenin on the production of inflammatory cytokines (e.g. TGF-ß, TNF-α) and pro-fibrosis factors in bronchoalveolar lavage fluid and pulmonary cells from lung tissues was also investigated. RESULTS: Our results showed, apigenin has anti-fibrosis effect by inhibition fibrosis related cytokines expression. And compared with apigenin in soluble form, the strategic release of apigenin is more effective in inhibiting pulmonary fibrosis and inflammation. CONCLUSION: Our finding suggested that apigenin loaded on polymeric carrier might be an effective treatment for pulmonary fibrosis patients.

Novel Amino-Pyridine Functionalized Chitosan Quaternary Ammonium Derivatives: Design, Synthesis, and Antioxidant Activity.

Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were used as functional groups to improve the antifungal activity of chitosan derivatives. The chitosan derivatives' antioxidant activity against hydroxyl-radical and 1,1-Diphenyl-2-picrylhydrazyl (DPPH)-radical was tested in vitro. The results showed that chitosan derivatives had better water solubility and stronger antioxidant activity compared with chitosan in all assays. Especially, compounds 3C and 3E (with 3-amino pyridine and 2,3-diamino pyridine as substitute respectively) exhibited stronger hydroxyl-radical and DPPH-radical scavenging ability than other synthesized compounds. These data demonstrated that the synergistic effect of the amino group and pyridine would improve the antioxidant activity of chitosan derivatives, and the position of the amino group on pyridine could influence the antioxidant property of chitosan derivatives.

Nickel-Catalyzed N-Alkylation of Acylhydrazines and Arylamines Using Alcohols and Enantioselective Examples.

A borrowing-hydrogen reaction between amines and alcohols is an atom-economic way to prepare alkylamines, ideally with water as the sole byproduct. Herein, nickel catalysts are used for direct N-alkylation of hydrazides and arylamines using racemic alcohols. Moreover, a nickel catalyst of (S)-binapine was used for an asymmetric N-alkylation of benzohydrazide with racemic benzylic alcohols.

[Survey on the early reperfusion therapy status in patients with ST-segment elevation myocardial infarction hospitalized in tertiary and secondary hospitals in Henan province].

OBJECTIVE: To observe the early reperfusion therapy status for patients with ST elevation acute myocardial infarction (STEMI) hospitalized in tertiary and secondary hospitals in Henan province. METHODS: Baseline data, early reperfusion treatment and in-hospital mortality of STEMI patients hospitalized in 17 hospitals in Henan province (8 tertiary hospitals, 9 secondary hospitals) from June 2011 to June 2012 were obtained using a uniformed questionnaire. RESULTS: One thousand six hundred and eighty six patients were enrolled, of which 886 patients were hospitalized in tertiary hospitals and 880 patients were early hospitalized in secondary hospitals. Six hundred and fifty four patients (38.8%, 654/1 686) underwent early reperfusion therapy (543 with thrombolysis and 111 with primary percutaneous coronary intervention (PCI)). There was no difference in the proportion of early reperfusion therapy between tertiary and secondary hospitals (40.1% (355/886) vs. 37.4% (299/800), P = 0.257). The median time from symptom onset to first medical contact, door-to-needle and door-to-balloon was 132 min, 18 min and 60 min, respectively. The median time from symptom onset to first medical contact (150 min vs. 120 min, P = 0.001), door-to-needle (30 min vs. 18 min, P = 0.003) and symptom onset-to-thrombolysis (3.5 h vs. 2.7 h, P = 0.001) were significantly longer in tertiary hospitals than in secondary hospitals. No difference was found in median time of door-to-balloon, symptom onset-to-primary PCI or symptom onset-to-elected PCI between tertiary and secondary hospitals (all P > 0.05). The proportion of door-to-needle ≤ 30 min was lower in tertiary hospitals than in secondary hospitals (46.4% (84/181) vs. 62.2% (153/246), P = 0.001). However, there was no difference in the proportion of door-to-balloon ≤ 90 min between tertiary and secondary hospitals (58.8% (60/102) vs. 57.1% (4/7), P = 1.000). In-hospital mortality was also similar between tertiary and secondary hospitals (5.8% (51/886) vs. 5.5% (44/800), P = 0.820). CONCLUSIONS: Early reperfusion rate is low, and thrombolysis is the main early reperfusion therapy in both tertiary and secondary hospitals in Henan province. Tertiary hospitals did not take advantage of their primary PCI capability. There is great room for improvement in early reperfusion therapy in tertiary and secondary hospitals.

Safety and efficacy of sitagliptin in combination with transient continuous subcutaneous insulin infusion (CSII) therapy in patients with newly diagnosed type 2 diabetes.

Sitagliptin was used as monotherapy or in combination with metformin, thiazolidinedione or sulfonylurea. It is not clear whether effects are enhanced or unique when in combination with transient continuous subcutaneous insulin infusion (CSII) therapy. The aim of this study was to assess the safety and efficacy of sitagliptin in combination with transient CSII therapy in patients with newly diagnosed type 2 diabetes. Eighty patients with newly diagnosed type 2 diabetes from July 2011 to May 2013 were recruited into the study. These patients were randomly divided into a CSII monotherapy group (group A, n = 40) or a sitagliptin in combination with CSII therapy group (group B, n = 40) and received insulin intensive therapy. Treatments were maintained for 2 weeks. 75g oral glucose tolerance test (OGTT) was performed before and after treatments, and the levels of glucose, insulin and C-peptide were examined. The results indicated that, compared with CSII therapy group, the level of plasma glucose significantly decreased, the levels of insulin and C-peptide strikingly increased and homeostasis model assessment for beta-cell function (HOMA-ß) and Insulinogenic index (Ins index) were improved in the group of sitagliptin in combination with CSII therapy. Above all, the incidence of hypoglycemia was lower, insulin doses were less and the rate of recovery to normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) determined by 75gOGTT was higher in the latter. So, Sitagliptin in combination with CSII therapy can be a new safe and effective therapy in patients with newly diagnosed type 2diabetes.

Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach.

BACKGROUND AND OBJECTIVE: To evaluate the effects of ischemia and reperfusion (IR) and ischemic preconditioning (IPC) on the metabolic activities of cytochrome P450 (CYP) isozymes in rats by a five-drug cocktail approach. METHODS: Cocktail approach was used to evaluate the influence of IR and IPC on the activities of CYP1A2, CYP2C9, CYP2E1, CYP2D6 and CYP3A4, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, respectively. Rats were randomly divided into IR, IPC and sham groups, and then injected the mixture of five probe drugs. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by a HPLC method with UV detection. The pharmacokinetic parameters were calculated by the software of DAS 2.0. RESULTS: The parameters including t(1/2ß), CLs, AUC, MRT and K10 exhibited a similar tendency for both IR and IPC groups. Compared with sham group, CLs and K10 of five probe drugs were significantly lower (p < 0.05), AUC and t(1/2ß) of five or some probe drugs were significantly increased in IR and IPC groups (p < 0.05). Compared with IPC group, CLs of five probe drugs were decreased and AUC were significantly increased in the IR group (p < 0.05). CONCLUSION: IR can variably decrease the activities of CYP isozymes in rats and this decrease can be attenuated by IPC.

Plasticization mechanism of biobased plasticizers comprising polyethylene glycol diglycidyl ether-butyl citrate with both long and short chains on poly(lactic acid).

Polylactic acid (PLA), a biodegradable polymer with low flexibility, is commonly plasticized with small molecules like tributyl citrate (TBC) for film production. However, these plasticizers, which lack chemical bonds or strong intermolecular interactions with the matrix, tend to migrate to the film surface over time. Their inclusion often compromises material strength for flexibility, increasing elongation at break but reducing tensile strength. In this research, by combining citric acid with n-butanol (B) and poly(ethylene glycol) diglycidyl ether (E), we synthesized three plasticizers, namely TE3, TE2B1, and TE1B2, to enhance the flexibility of PLA. TE2B1 and TE1B2 are equipped with butyl ester groups that offer effective plasticizing effects. Additionally, the incorporation of long-chain alkyl featuring epoxy groups can boost the interaction with PLA. The results showed that the epoxy groups of the long-chain alkyl plasticizers can improve the elongation at break without compromising tensile strength significantly. The migration of plasticizer from PLA matrix can be reduced by strong interactions like chemical bonds, entanglements, and hydrogen bonding with PLA. TE1B2 demonstrated the best plasticizing effect. Adding 15 portions of TE1B2 and TBC separately increased PLA's elongation at break to 304 % and 242 %, with tensile strengths of 36.1 MPa and 22.3 MPa, respectively.

Bio-based epoxidized soybean oil branched cardanol ethers as compatibilizers of polybutylene succinate (PBS)/polyglycolic acid (PGA) blends.

Blending poly(butylene succinate) (PBS) with another biodegradable polymer, polyglycolic acid (PGA), has been demonstrated to improve the barrier performance of PBS. However, blending these two polymers poses a challenge because of their incompatibility and large difference of their melting temperatures. In this study, we synthesized epoxidized soybean oil branched cardanol ether (ESOn-ECD), a bio-based and environmentally friendly compatibilizer, and used it to enhance the compatibility of PBS/PGA blends. It was demonstrated that the terminal carboxyl/hydroxyl groups of PBS and PGA can react with ESOn-ECD in situ, leading to branching and chain extension of PBS and PGA. The addition of ESO3-ECD to the blend considerably diminished the dispersed phase of PGA. Specifically, in comparison to the PBS/PGA blend without a compatibilizer, the diameter of the PGA phase decreased from 2.04 µm to 0.45 µm after the addition of 0.7 phr of ESO3-ECD, and the boundary between the two phases became difficult to distinguish. Additionally, the mechanical properties of the blends were improved after addition of ESO3-ECD. This research expands the potential applications of these materials and promotes the use of bio-based components in blend formulations.

[Spatiotemporal Evolution Characteristics of Carbon Sources and Carbon Sinks and Carbon Balance Zoning in the Yangtze River Delta Region].

Mastering the spatiotemporal evolution laws of carbon sources and sinks is of great significance to promote the coordinated development of regional low-carbon, improve the science of carbon reduction and sink increase policies, and realize the goal of "double carbon." Taking 41 cities in the Yangtze River Delta Region as the research object, this study analyzed the spatiotemporal evolution characteristics of carbon sources and sinks in the Yangtze River Delta Region from 2000 to 2020 and conducted the carbon balance zoning. The results were as follows： ① The carbon emissions increased rapidly in the Yangtze River Delta Region from 2000 to 2011 but with some fluctuations after 2011. Carbon sinks increased slowly in the Yangtze River Delta Region from 2000 to 2020. The regional differences in carbon emissions and carbon sinks were significant, and the spatial pattern was relatively stable. ② The carbon compensation rate in the Yangtze River Delta Region showed a downward trend, and the carbon productivity, energy utilization efficiency, and carbon ecological support capacity were constantly enhanced. Interregional differences were the main source of carbon compensation rate in the Yangtze River Delta Region. Both the carbon compensation rate and carbon ecological support coefficient showed a spatial pattern of "high in the west and low in the east, high in the south and low in the north." The areas with high carbon economy contributive coefficient were concentrated in the central and southern areas of the Yangtze River Delta regions, and the areas with low carbon economy contributive coefficient were concentrated in Anhui Province. ③ Based on the carbon economy contributive coefficient and the carbon ecological support coefficient, cities in the Yangtze River Delta Region were classified into low-carbon maintenance areas, economic development areas, carbon sink development areas, and comprehensive optimization areas. Recommendations were proposed for each category of cities in order to promote the coordinated development of regional low-carbon and realize the goal of "double carbon".