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1.
J Transl Med ; 22(1): 274, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38475814

ABSTRACT

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.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Mice , Animals , Receptors, Chimeric Antigen/metabolism , Antigens, CD19/genetics , Antigens, CD19/metabolism , Cytotoxicity, Immunologic/genetics , Cell Line, Tumor , Killer Cells, Natural , Immunotherapy, Adoptive , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , RNA, Messenger/metabolism
2.
Int J Biol Macromol ; 259(Pt 2): 129319, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38211920

ABSTRACT

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.


Subject(s)
Butylene Glycols , Ethers , Phenols , Polyesters , Polymers , Soybean Oil , Polyglycolic Acid
3.
Molecules ; 28(14)2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37513322

ABSTRACT

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.

4.
Small ; 19(37): e2301512, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37154221

ABSTRACT

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.

5.
Materials (Basel) ; 16(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36902978

ABSTRACT

In the present work, the two-phase mixture (HTLc) of hydrotalcite and its oxide were used to improve the barrier properties, UV resistance and antimicrobial activity of Poly(ethylene terephthalate) (PET) for their application in liquid milk packaging. Firstly, CaZnAl-CO3-LDHs with a two-dimensional layered structure were synthesized by hydrothermal method. CaZnAl-CO3-LDHs precursors were characterized by XRD, TEM, ICP and dynamic light scattering. A series of PET/HTLc composite films were then prepared, characterized by XRD, FTIR and SEM, and a possible mechanism of the composite films with hydrotalcite was proposed. Barrier properties to water vapor and oxygen have been studied in PET nanocomposites, as well as their antibacterial efficacy by the colony technique and their mechanical properties after exposure to UV irradiation for 24 h. By the presence of 1.5 wt% HTLc in the PET composite film, the oxygen transmission rate (OTR) was reduced by 95.27%, the water vapor transmission rate was reduced by 72.58% and the inhibition against Staphylococcus aureus and Escherichia coli was 83.19% and 52.75%. Moreover, a simulation of the migration process in dairy products was used to prove the relative safety. This research first proposes a safe technique for fabricating hydrotalcite-based polymer composites with a high gas barrier, UV resistance and effective antibacterial activity.

6.
ACS Omega ; 8(1): 663-672, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36643425

ABSTRACT

The poly(butylene adipate-co-terephthalate) (PBAT)/thermoplastic starch (TPS) film stands out owing to its acceptable price, low impact on the environment, and excellent mechanical properties. The main objective of this study was to improve the antioxidant properties of the PBAT/TPS film by incorporation of quercetin (Q) through the extrusion blow process. Another specific objective was to incorporate the organically modified montmorillonite (OMMT) to prolong the release of Q and improve the poor barrier properties of the PBAT/TPS/Q film. The films were analyzed in terms of their morphology, mechanical properties, gas and water barrier properties, and antioxidant and anti-UV properties. Optimization of the OMMT content resulted in a fiber-like, co-continuous morphology of the PBAT/TPS/Q film. The incorporation of quercetin enhanced the antioxidant and anti-UV properties of the PBAT/TPS film, while OMMT improved the mechanical properties, ultraviolet barriers, and gas and water barrier properties. The results show that the films incorporating Q and OMMT provided the oxygen and water barrier by up to 94 and 54%, respectively. Also, the amount of polymer required for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition is as low as 0.03 g, and the UV transmission rate was reduced by about 50%. Moreover, PBAT/TPS/Q/OMMT films successfully delayed the decay of the banana and blueberry due to their excellent antioxidant properties and suitable water vapor permeability.

7.
ACS Appl Mater Interfaces ; 15(3): 4569-4579, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36642890

ABSTRACT

Highly fluorescent covalent organic frameworks (COFs) are rarely obtained because of the π-π stacked layers with aggregation-caused quenching behavior. Unarguably, highly fluorescent COFs with tunable emission colors are even more rarely achieved. Herein, a general strategy to modify the classical COF material (named COF-1) by different fluorescent molecules via N → B interaction was developed. In this method, the boron-containing COF-1 acted as a porous and crystalline matrix as well as a reaction partner of Lewis acid; after interacting with fluorescent molecules with the anchoring group of pyridine (Lewis base), COF-1 takes a gorgeous transfiguration from a non-emissive powder into a highly fluorescent COF material with tunable emission colors. This disclosed method endowed the typical COFs with new emissive life and is speculated with the general research concept for all boron-containing COFs. Benefiting from the prominent fluorescent emission in the aggregation state, sensitive probes toward amines are achieved.

8.
Dig Dis Sci ; 68(5): 1864-1872, 2023 05.
Article in English | MEDLINE | ID: mdl-36436157

ABSTRACT

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.


Subject(s)
Gastritis, Atrophic , Gastritis , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Serotonin , Gastritis/metabolism , Gastric Mucosa/metabolism , Gastritis, Atrophic/metabolism , Stem Cells/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism
9.
Front Microbiol ; 13: 993237, 2022.
Article in English | MEDLINE | ID: mdl-36118207

ABSTRACT

Shewanella baltica is the dominant bacterium that causes spoilage of seafood. RpoS is an alternative sigma factor regulating stress adaptation in many bacteria. However, the detailed regulatory mechanism of RpoS in S. baltica remains unclear. This study aims to investigate the regulatory function of RpoS on spoilage activity and adhesion ability in S. baltica. Results revealed that RpoS had no effect on the growth of S. baltica, but positively regulated the spoilage potential of S. baltica accompanied by a slower decline of total volatile basic nitrogen, lightness, and the sensory score of fish fillets inoculated with rpoS mutant. RpoS negatively regulated the adhesion ability, which was manifested in that the bacterial number of rpoS mutant adhered to stainless steel coupon was higher than that of the S. baltica in the early stage, and the biofilm formed on glass slide by rpoS mutant was thicker and tighter compared with S. baltica. Transcriptomic analysis showed that a total of 397 differentially expressed genes were regulated by RpoS. These genes were mainly enrichment in flagellar assembly, fatty acid metabolism/degradation, and RNA degradation pathways, which were associated with motility, biofilm formation and cold adaptation. This study demonstrated that RpoS is a primary regulator involved in flagellar assembly mediated biofilm formation and cold adaptation-related spoilage activity of S. baltica. Our research will provide significant insights into the control of microbiological spoilage in seafood.

10.
Small ; 18(35): e2203104, 2022 09.
Article in English | MEDLINE | ID: mdl-35931455

ABSTRACT

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.


Subject(s)
Brain Waves , Ion Channels , Ion Transport , Ions , Light
11.
ACS Omega ; 7(24): 21280-21290, 2022 Jun 21.
Article in English | MEDLINE | ID: mdl-35935288

ABSTRACT

Poly(glycolic acid) (PGA) is a semicrystalline biodegradable polyester with high gas barrier properties. However, due to its poor processability and low ductility, PGA could hardly find applications in the packaging field. Here, a strategy was adopted for in situ generation of high-aspect-ratio flexible microfibrils with strong interface affinity for the PGA matrix. Because poly(butylene adipate-co-terephthalate) (PBAT) possesses impressive ductility, it was selected as the "fibrillar toughening phase" to enhance the ductility of PGA. Moreover, a chain extender was used to enhance the interfacial adhesion between the two polymers. The extrusion blown film technique was then used to develop fully biodegradable PGA/PBAT films with a superior combination of excellent barrier performance and robust mechanical properties. The PBAT phase can in situ form microfibrils under the influence of extensional flow. Simultaneously, the synergetic function of the extensional flow field could effectively promote the motion of the PGA molecular chain to develop an oriented crystalline microstructure. Because of the aligned oriented lamellar crystal of PGA and oriented PBAT fibril structures serving as robust "barrier walls" 60PGA/ADR blown films demonstrated dramatically improved resistance to oxygen and water vapor, with 59 and 44 times lower oxygen permeability and water vapor permeability, respectively, when compared to the neat PBAT blown film. As a result, PGA/PBAT blown films offer a variety of benefits, including superior ductility, toughness, and a strong gas barrier property. The potential of these films to degrade makes them a viable contender for replacing classical nondegradable packing films.

12.
Front Endocrinol (Lausanne) ; 13: 921645, 2022.
Article in English | MEDLINE | ID: mdl-35966080

ABSTRACT

Purpose: Pheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL. Methods: We established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues. Results: Overall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL. Conclusion: Our results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL.


Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Pheochromocytoma , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/pathology , Humans , Mutation , Paraganglioma/genetics , Paraganglioma/pathology , Pheochromocytoma/genetics , Pheochromocytoma/pathology , Protein-Tyrosine Kinases/genetics
13.
Int J Biol Macromol ; 214: 1-9, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35705124

ABSTRACT

Sweet cherry is prone to senesce and decay due to high postharvest respiration rate and fungal infection. The effects of natamycin-chitosan coating on physicochemical and microbial properties of sweet cherries stored at 4 °C were investigated. Scanning electron microscopy results revealed that natamycin was more uniformly distributed on sweet cherry pericarps with the help of chitosan coating. Respiration rate of sweet cherries was suppressed by chitosan coating during the storage and as a result, total soluble solids (13.53 %-13.80 %) and titratable acidity (0.91 %-0.93 %) were remained higher values and weight loss (2.54 %-2.85 %) was decreased in chitosan and natamycin-chitosan groups. Although both natamycin and chitosan were effective in inhibiting yeast and mold, sweet cherries treated with the combination of natamycin and chitosan showed significantly lower yeast and mold count (3.31 log CFU/g) and decay rate (1.67 %) compared with control. Natamycin combined chitosan inhibited the pathogenic fungi of sweet cherries, such as Alternaria, Cladosporium and Penicillium. These results indicated that postharvest natamycin-chitosan coating has great advantages in maintaining fruit quality, inhibiting fungi, and reducing decay rate of sweet cherry.


Subject(s)
Chitosan , Prunus avium , Chitosan/chemistry , Food Preservation/methods , Fruit/chemistry , Fungi , Natamycin/pharmacology , Prunus avium/chemistry , Saccharomyces cerevisiae
14.
Small ; 18(20): e2107600, 2022 05.
Article in English | MEDLINE | ID: mdl-35324064

ABSTRACT

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.


Subject(s)
Polymers , Salinity , Electricity , Physical Phenomena
15.
Polymers (Basel) ; 14(3)2022 Jan 26.
Article in English | MEDLINE | ID: mdl-35160473

ABSTRACT

Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable polymer synthesized from petrochemical resources. PBAT has an exceptionally high elongation at break values which makes it one of the most promising substitutes for LDPE packaging films. However, the applicability of PBAT films is still limited by low strength and high production costs. In this work, we used polyethylene glycol 600 (PEG-600) as a coating agent to modify the surface of calcium carbonate and improve compatibility with the polymer matrix. A series of PBAT/CaCO3 composite films having different CaCO3 particle size and content of coating agent was prepared using extrusion blow molding. The effect of particle size of CaCO3 filler and the content of a coating agent on the mechanical and rheological properties of composite films have been studied. The biodegradation properties have been tested by burying the samples in soil or keeping them in artificial seawater for 90 days. It was shown that the addition of PEG-600 improves compatibility between the matrix and CaCO3 filler as polar -OH groups of PEG have a high affinity toward the polar surface of CaCO3. Moreover, the hydrophilicity of PEG-600 increased the diffusivity of water molecules and facilitated PBAT degradation. This work provides experimental data and theoretical guidance that support the development of high-performance PBAT/calcium carbonate films for the single use packaging industry.

16.
Polymers (Basel) ; 13(22)2021 Nov 16.
Article in English | MEDLINE | ID: mdl-34833261

ABSTRACT

Polymer/clay composites are an innovative class of materials. In this study, we present a facile method for the preparation of biodegradable and robust PLA/organomodified montmorillonite (OMMT) composite films with excellent gas barrier performance. When the design of PLA/OMMT composite films, in addition to making OMMT have good intercalation effect in the matrix, the compatibility of intercalating polymer and matrix should also be considered. In this work, two polymers with high gas barrier properties, namely poly(vinyl alcohol) (PVA) and ethylene vinyl alcohol copolymer (EVOH), were selected to intercalate OMMT. The morphology and microstructures of the prepared PLA/PVA/OMMT and PLA/EVOH/OMMT composites were characterized by the X-ray diffraction measurement, scanning electron microscopy, and differential scanning calorimetry. It was shown that the good dispersibility of PVA in the PLA matrix, rather than the intercalation effect, was responsible for the improved gas barrier and mechanical properties of PLA/PVA/OMMT composite. The elongation at break increases from 4.5% to 22.7% when 1 wt % PVA is added to PLA/OMMT. Moreover, gas barrier of PLA/PVA1/OMMT measured as O2 permeability is 52.8% higher than that of neat PLA. This work provides a route to intercalate OMMT interlayer with high gas barrier polymers and thus can be a useful reference to fabricate PLA/OMMT composites with improved gas barrier and mechanical properties. A comparison of oxygen permeabilities with existing commercial packaging films indicates that the biodegradable PLA/PVA/OMMT may serve as a viable substitute for packaging film applications.

17.
Comput Math Methods Med ; 2021: 1341644, 2021.
Article in English | MEDLINE | ID: mdl-34650619

ABSTRACT

BACKGROUND: Patients with stable chronic obstructive pulmonary disease (COPD) have been observed to benefit from tiotropium bromide. However, there are few studies of tiotropium bromide on sputum and sputum viscosity. To evaluate the effect of tiotropium bromide on mucus hypersecretion, a randomized, double-blind controlled trial was performed. METHODS: 120 cases of patients with pulmonary function grade II were divided into two groups, which include the treatment group given tiotropium bromide powder inhalation (18 µg, inhalation, QD) and the control group given formoterol fumarate powder inhalation (12 µg, inhalation, BID) plus ambroxol hydrochloride tablets (60 mg, oral, TID). After 3 months of treatment, the pulmonary function and α 1-acid glycoprotein (α 1-AGP) in sputum were detected, and the changes of glycoprotein and Ca2+ content were evaluated by Miller classification. RESULTS: Three patients (2 cases in the treatment group and 1 case in the control group) were dropped due to loss of follow-up, and 117 cases of patients were enrolled in this study. After 3 months of treatment, the sputum character score, α1-acid glycoprotein, Ca2+ content, and lung function of the two groups were significantly improved; group comparison analyses revealed that there was no significant difference in the content of α 1-AGP, Ca2+ in sputum, and lung function between the two groups (P > 0.05), but the improvement of sputum properties was significant (P < 0.05), and the treatment group was better than the control group (t = -2.77; P = 0.007). CONCLUSIONS: Inhaled tiotropium bromide can effectively inhibit the mucus hypersecretion in stable COPD patients, improve the sputum properties and lung function of patients, and improve the quality of life of patients.


Subject(s)
Mucus/drug effects , Mucus/physiology , Muscarinic Antagonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Tiotropium Bromide/therapeutic use , Administration, Inhalation , Ambroxol/administration & dosage , Calcium/metabolism , Computational Biology , Double-Blind Method , Formoterol Fumarate/administration & dosage , Humans , Muscarinic Antagonists/administration & dosage , Orosomucoid/metabolism , Pulmonary Ventilation/drug effects , Quality of Life , Sputum/drug effects , Sputum/physiology , Tiotropium Bromide/administration & dosage
18.
J Control Release ; 335: 449-456, 2021 07 10.
Article in English | MEDLINE | ID: mdl-34029632

ABSTRACT

COVID-19 pandemic has resulted in an unprecedented global public health crisis. It is obvious that SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Since obvious advantages including fast manufacturing speed, potent immunogenicity and good safety profile, six mRNA vaccines have been used to prevent SARS-CoV-2 infections in clinic with lipid nanoparticles (LNP) formulation via intramuscular injection. In this work, we first constructed RBD-encoding mRNA (RBD-mRNA) formulated in liposomes (LPX/RBD-mRNA) and investigated the influence of administration routes on the immunogenicity. LPX/RBD-mRNA can express RBD in vivo and successfully induced SARS-CoV-2 RBD specific antibodies in the vaccinated mice, which efficiently neutralized SARS-CoV-2 pseudotyped virus. Moreover, the administration routes were found to affect the virus neutralizing capacity of sera derived from the immunized mice and the types (Th1-type and Th2-type) of cellular immune responses. This study indicated that liposome-based RBD-mRNA vaccine with optimal administration route might be a potential candidate against SARS-CoV-2 infection with good efficacy and safety.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Liposomes , Mice , Mice, Inbred BALB C , Pandemics , RNA, Messenger , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
19.
Sensors (Basel) ; 21(1)2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33401444

ABSTRACT

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.

20.
ACS Omega ; 5(30): 18675-18684, 2020 Aug 04.
Article in English | MEDLINE | ID: mdl-32775869

ABSTRACT

A high gas barrier performance should be ensured in case of biodegradable packing applications. However, the gas barrier properties of the biodegradable poly(lactic acid) (PLA) are not much effective. Nanocomposites can provide innovative solutions to enhance the barrier performance. In this study, different weight percentages of organically modified montmorillonite (OMMT) (0, 2, 4, 6, 8, and 10 wt %)-incorporated PLA/OMMT nanocomposites were prepared by melt mixing. Ethylene glycol diglycidyl ether (EGDE) was used to regulate the interlayer spacing of OMMT and increase the PLA crystallinity to further improve the gas barrier performance of the PLA/OMMT films. The crystallinity of PLA was significantly improved because EGDE-modified OMMT served as an efficient nucleating agent. The PLA/EGDE/OMMT films demonstrated a unique structure such that the adjacent OMMT layers were linked through the PLA crystals that serve as a bridge with respect to the spaces between the OMMT layers. The O2 permeability of the PLA/EGDE4/OMMT-6 film decreased by approximately 79% when compared with that of the neat PLA film. X-ray diffraction and differential scanning calorimetry analyses denoted that the reduced oxygen permeability of the PLA/EGDE4/OMMT-6 film can be primarily attributed to the high crystallinity of the PLA matrix and the bridging effect of the PLA crystals between two adjacent layers. Based on the experimental results, the relation between the relative permeability and vol % OMMT is in good agreement with that of the predicted values obtained using the Bharadwaj model when S = 0. The added EGDE weakened the thermal stability and tensile strength, mainly because of degradation of the hydroxyl groups of EGDE formed by epoxy ring opening, and these hydroxyl groups can promote PLA matrix degradation. However, the practical application temperature of the packaging film is considerably lower than the thermal decomposition temperature; therefore, the reduction of the thermal decomposition temperature does not affect the use of the packaging film.

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