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1.
Br J Nutr ; 131(2): 321-332, 2024 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-37642161

RESUMEN

Despite observed ethnic differences in eating patterns and obesity, evidence in China is limited. This study examined ethnic differences in eating patterns and their associations with weight outcomes among multi-ethnic adults in West China. A cross-sectional survey collected self-reported data on demographics, eating behaviours, weight and height in 2021. Principal component analysis and multivariate regression were conducted to identify eating patterns and examine their associations with weight outcomes. In total, 4407 subjects aged ≥ 18 years were recruited across seven provinces in West China. Four eating patterns were identified: 'meat-lover' - characterised by frequent consumption of meat and dairy products, 'indulgent' - by frequent intakes of added salt, sugar, alcohol and pickled food, 'diversified-eating' - by frequently consuming food with diversified cooking methods and eating out and 'nutri-health-concerned' - by good food hygiene behaviours and reading food labels. Ethnic differences in eating patterns were observed. Compared with Han, Hui were less likely to exhibit meat-lover or diversified-eating patterns; Tibetans were less likely to have meat-lover or nutri-health-concerned patterns; Mongolians were more likely to have indulgent pattern. BMI was positively associated with meat-lover pattern in both genders (exp(ß): 1·029; 95 % CI: 1·001, 1·058 for men; 1·018; 1·000, 1·036 for women) and negatively associated with nutri-health-concerned pattern in women (0·983; 0·966, 1·000). Mongolians were two times more likely to be overweight/obese than Han (OR: 3·126; 1·688, 5·790). Considerable ethnic differences existed in eating patterns in West China. Mongolians were more likely to be overweight/obese, which was associated with their indulgent eating patterns. Ethnic-specific healthy eating intervention programs are needed.


Asunto(s)
Dieta , Conducta Alimentaria , Obesidad , Sobrepeso , Adulto , Femenino , Humanos , Masculino , China/epidemiología , Estudios Transversales , Obesidad/epidemiología , Etnicidad , Pueblos del Este de Asia
2.
Ann Intern Med ; 176(7): 922-933, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37335994

RESUMEN

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.


Asunto(s)
Terapia por Acupuntura , Antieméticos , Complicaciones del Embarazo , Embarazo , Niño , Femenino , Humanos , Doxilamina/efectos adversos , Piridoxina/uso terapéutico , Piridoxina/efectos adversos , Antieméticos/uso terapéutico , Calidad de Vida , Vómitos/tratamiento farmacológico , Vómitos/inducido químicamente , Náusea/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Terapia por Acupuntura/efectos adversos
3.
Molecules ; 29(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38474488

RESUMEN

Supercapacitors (SCs) are a novel type of energy storage device that exhibit features such as a short charging time, a long service life, excellent temperature characteristics, energy saving, and environmental protection. The capacitance of SCs depends on the electrode materials. Currently, carbon-based materials, transition metal oxides/hydroxides, and conductive polymers are widely used as electrode materials. However, the low specific capacitance of carbon-based materials, high cost of transition metal oxides/hydroxides, and poor cycling performance of conductive polymers as electrodes limit their applications. Copper-sulfur compounds used as electrode materials exhibit excellent electrical conductivity, a wide voltage range, high specific capacitance, diverse structures, and abundant copper reserves, and have been widely studied in catalysis, sensors, supercapacitors, solar cells, and other fields. This review summarizes the application of copper-sulfur compounds in SCs, details the research directions and development strategies of copper-sulfur compounds in SCs, and analyses and summarizes the research hotspots and outlook, so as to provide a reference and guidance for the use of copper-sulfur compounds.

4.
Small ; 19(5): e2205119, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36440683

RESUMEN

A new perspective is proposed in the design of pore-space-partitioned MOFs that is focused on ligand symmetry properties sub-divided here into three hierarchical levels: 1) overall ligand, 2) ligand substructure such as backbone or core, and 3) the substituent groups. Different combinations of the above symmetry properties exist. Given the close correlation between nature of chemical moiety and its symmetry, such a unique perspective into ligand symmetry and sub-symmetry in MOF design translates into the influences on MOF properties. Five new MOFs have been prepared that exhibit excellent hydrothermal stability and high-performance adsorption properties with potential applications such as C3 H6 /C2 H4 and C2 H2 /CO2 selective adsorption. The combination of high stability with high benzene/cyclohexane selectivity of ≈13.7 is also of particular interest.

5.
Small ; 19(50): e2304918, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37626450

RESUMEN

Developing composite materials with the synergistic effects of heterogeneous structures and multiple components is considered as a promising strategy to achieve high-performance electromagnetic wave (EMW) absorbers. To further satisfy the demand of broadband and strong microwave absorption, a novel NiS/carbon nanofibers (CNFs)/porous carbon composite is successfully synthesized by hydrothermal and chemical vapor deposition using lotus leaves as a biomass carbon source. A few carbon nanotubes (CNTs) and uniformly dispersed Ni nanocrystals have also been found in the hybrid. Benefiting from the porous structure derived from lotus leaves, the combination of dielectric NiS, conductive carbon nanomaterials, and magnetic Ni nanoparticles, together with the three-dimensional conductive network of CNFs and CNTs, the remarkable EMW absorption properties with a minimum reflection loss up to -67.65 dB have been achieved at merely 2.32 mm. Besides, the widest effective absorption band can reach 5.9 GHz with a thin thickness of 2.07 mm, covering almost the entire Ku band. In addition, under the incident angle of 31°, the radar cross-section reduction value of LNSF-600 can reach 42.88 dBm2. Therefore, this work provides an efficient and facile method for manufacturing outstanding biomass-derived EMW absorbers.

6.
Small ; 19(45): e2303540, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37420325

RESUMEN

Pore space partition (PSP) is an effective materials design method for developing high-performance small-pore materials for storage and separation of gas molecules. The continued success of PSP depends on broad availability and judicious choice of pore-partition ligands and better understanding of each structural module on stability and sorption properties. Here, by using substructural bioisosteric strategy (sub-BIS), a dramatic expansion of pore-partitioned materials is targeted by using ditopic dipyridyl ligands with non-aromatic cores or extenders, as well as by expanding heterometallic clusters to uncommon nickel-vanadium and nickel-indium clusters rarely known before in porous materials. The dual-module iterative refinement of pore-partition ligands and trimers leads to remarkable enhancement of chemical stability and porosity. Here a family of 23 pore-partitioned materials synthesized from five pore-partition ligands and seven types of trimeric clusters is reported. New materials with such compositionally and structurally diverse framework modules reveal key factors that dictate stability, porosity, and gas separation properties. Among these, materials based on heterometallic vanadium-nickel trimeric clusters give rise to the highest long-term hydrolytic stability and remarkable uptake capacity for CO2 , C2 H2 /C2 H4 /C2 H6 , and C3 H6 /C3 H8 hydrocarbon gases. The breakthrough experiment shows the potential application of new materials for separating gas mixtures such as C2 H2 /CO2 .

7.
Chemistry ; 29(13): e202203547, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36464911

RESUMEN

A multi-stage core-expansion method is proposed here as one component of the integrative binding-site/extender/core-expansion (BEC) strategy. The conceptual deconstruction of the partitioning ligand into three editable parts draws our focus onto progressive core expansion and allows the optimization of both acetylene uptake and selectivity. The effectiveness of this strategy is shown through a family of eight cationic pore-partitioned materials containing three different partitioning ligands and various counter anions. The optimized structure, Co3 -cpt-tph-Cl (Hcpt=4-(p-carboxyphenyl)-1,2,4-triazole, H-tph=(2,5,8-tri-(4-pyridyl)-1,3,4,6,7,9-hexaazaphenalene) with the largest surface area and highest C2 H2 uptake capacity (200 cm3 /g at 298 K), also exhibits (desirably) the lowest CO2 uptake and hence the highest C2 H2 /CO2 selectivity. The successful boost in both C2 H2 capacity and IAST selectivity allows Co3 -cpt-tph-Cl to rank among the best crystalline porous materials, ionic MOFs in particular, for C2 H2 uptake and C2 H2 /CO2 experimental breakthrough separation.

8.
Langmuir ; 38(7): 2392-2400, 2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35148119

RESUMEN

Two kinds of carbon nanoproducts with different microstructures, namely, carbon nanotubes (CNTs) and carbon nanofibers (CNFs), were grown on the surface of carbon fibers (CFs) by chemical vapor deposition (CVD) at low temperatures to improve the interface bonding between fibers and resins. The short-beam method and the micro-debonding method were used to test the interlaminar shear strength (ILSS) and interfacial shear strength (IFSS) of the composites. The results showed that the contribution of CNTs to the improvement of interfacial properties was better than that of CNFs. Specifically, the ILSS and IFSS of the CF-CNFs/epoxy composites increased by 18.59 and 24.39%, respectively, while the ILSS and IFSS of the CF-CNTs/epoxy composites increased by 26.97 and 47.79%, respectively. Compared with CNFs, the high degree of graphitization of CNTs and the π-interactions with the resin can better induce the formation of an interphase between the fiber and the resin, which suppressed the initiation of cracks and extended the propagation path of the cracks in the composites.

9.
Angew Chem Int Ed Engl ; 61(13): e202116064, 2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35098623

RESUMEN

We report here a strategy for making anionic pacs type porous materials by combining pore space partition with charge reallocation. The method uses the first negatively charged pore partition ligand (2,5,8-tri-(4-pyridyl)-1,3,4,6,7,9-hexaazaphenalene, H-tph) that simultaneously enables pore partition and charge reallocation. Over two dozen anionic pacs materials have been made to demonstrate their excellent chemical stability and a high degree of tunability. Notably, Ni3 -bdt-tph (bdt=1,4-benzeneditetrazolate) exhibits month-long water stability, while CoV-bdt-tph sets a new benchmark for C2 H2 storage capacity under ambient conditions for ionic MOFs. In addition to tunable in-framework modules, we show feasibility to tune the type and concentration of extra-framework counter cations and their influence on both stability and capability to separate industrial C3 H8 /C3 H6 and C6 H6 /C6 H12 mixtures.

10.
J Am Chem Soc ; 143(36): 14470-14474, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34464126

RESUMEN

State-of-the-art MOFs are generally known for chemical stability at one end of the pH scale (i.e., pH < 0 or pH > 14). Herein, we report new Cr-MOFs capable of withstanding extreme pH conditions across approximately 16 pH units from pH < 0 to pH > 14, likely the largest observed pH range for MOFs. The integration of multiple stability-enhancing factors including nonlabile Cr3+, mixed Cr-N and Cr-O cross-links, and the highest possible connectivity by Cr3O trimers enables extraordinary chemical stability confirmed by both PXRD and gas adsorption. Notably, the base stability is much higher than literature Cr-MOFs, thereby revitalizing Cr-MOF's viability in the pursuit for the most chemically stable MOFs. Among known cationic MOFs, the chemical stability of these new Cr-MOFs is unmatchable, to our knowledge. These Cr-MOFs can be developed into multiseries of isoreticular MOFs with a rich potential for functionalization, pore size, and pore geometry engineering and applications.

11.
Small ; 17(22): e2003167, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32844577

RESUMEN

Metal trimers [M3 (O/OH)](OOCR)6 are among the most important structural building blocks. From these trimers, a great success has been achieved in the design of 6- or 9-connected framework materials with various topological features and outstanding gas-sorption properties. In comparison, 8-connected trimer-based metal-organic frameworks (MOFs) are rare. Given multiple competitive pathways for the formation of 6- or 9-connected frameworks, it remains challenging to identify synthetic or structural parameters that can be used to direct the self-assembly process toward trimer-based 8-connected materials. Here, a viable strategy called angle bending modulation is revealed for creating a prototypical MOF type based on 8-connected M3 (OH)(OOCR)5 (Py-R)3 trimers (M = Zn, Co, Fe). As a proof of concept, six members in this family are synthesized using three types of ligands (CPM-80, -81, and -82). These materials do not possess open-metal sites and show excellent uptake capacity for various hydrocarbon gas molecules and inverse C2 H6 /C2 H4 selectivity. CPM-81-Co, made from 2,5-furandicarboxylate and isonicotinate, features selectivity of 1.80 with high uptake capacity for ethane (123 cm3 g-1 ) and ethylene (113 cm3 g-1 ) at 298 K and 1 bar.

12.
FASEB J ; 34(9): 11772-11785, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32652815

RESUMEN

Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Δ12,14 -prostaglandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders.


Asunto(s)
PPAR gamma/metabolismo , Prostaglandina D2/análogos & derivados , Sepsis/metabolismo , Transducción de Señal/efectos de los fármacos , Timopentina/farmacología , Animales , Ciego/cirugía , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Ligadura/efectos adversos , Masculino , Ratones Endogámicos C57BL , Prostaglandina D2/metabolismo , Punciones/efectos adversos , Sepsis/etiología , Sepsis/mortalidad , Tasa de Supervivencia
13.
Mol Pharm ; 18(4): 1758-1767, 2021 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-33656348

RESUMEN

In this study, various structurally similar aliphatic dicarboxylic acids, namely, succinic acid, glutaric acid, adipic acid, and pimelic acid, were employed as coformers to obtain phase pure cocrystals with berberine chloride (BCl) by a slow solvent evaporation method. The structures of the four novel salt-cocrystals of BCl were determined by single crystal X-ray diffraction analysis and their solid-state properties were characterized. Compared with BCl·2H2O, all the cocrystals showed a higher melting point, improved powder dissolution and intrinsic dissolution rate (IDR), and lower hygroscopicity. It is noteworthy that the melting points and IDRs of these cocrystals exhibit an odd-even alternation with the carbon chain length of the acids.


Asunto(s)
Berberina/farmacocinética , Ácidos Dicarboxílicos/química , Excipientes/química , Administración Oral , Berberina/administración & dosificación , Berberina/química , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Composición de Medicamentos/métodos , Liberación de Fármacos , Enlace de Hidrógeno , Difracción de Polvo , Solubilidad
14.
Nanotechnology ; 32(28)2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33823501

RESUMEN

Carbon nanotubes (CNTs) were continuously grown on the surface of the moving carbon fiber by chemical vapor deposition method using a custom-designed production line to prepare composite reinforcements on a large-scale. The systematic study of different parameters affecting the CNT growth revealed simple growth kinetics, which helps to control the surface morphology and structural quality of CNTs. Since hydrogen maintains the activity of the catalyst, it promotes the growth of CNTs in a continuous process. The increase of acetylene partial pressure promotes the accumulation of amorphous or graphite carbon on the catalyst surface, resulting in the decrease of CNT growth rate when acetylene concentration reaches 40%. The growth temperature significantly affects the CNT diameter and structural quality. As the temperature increases, the crystallinity of the tube wall increases obviously, and the CNT diameter increases due to the aggregate growth of the catalyst particles. According to the Arrhenius formula, the apparent activation energy is observed to be 0.67 eV, which proves that both bulk diffusion and surface diffusion exist when activated carbon passes through the catalyst to form CNTs.

15.
Bioorg Chem ; 113: 104994, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34052738

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure-activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 µM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.


Asunto(s)
Berberina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores de PCSK9 , Berberina/síntesis química , Berberina/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Estructura Molecular , Proproteína Convertasa 9/metabolismo , Relación Estructura-Actividad
16.
Bioorg Chem ; 115: 105196, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34333425

RESUMEN

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1ß, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.


Asunto(s)
Antivirales/farmacología , Piperidinas/farmacología , Quinolizidinas/farmacología , SARS-CoV-2/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Animales , Antivirales/síntesis química , Antivirales/farmacocinética , Antivirales/toxicidad , Catepsina B/antagonistas & inhibidores , Chlorocebus aethiops , Citocinas/metabolismo , Células HEK293 , Humanos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Piperidinas/síntesis química , Piperidinas/farmacocinética , Piperidinas/toxicidad , Quinolizidinas/síntesis química , Quinolizidinas/farmacocinética , Quinolizidinas/toxicidad , Ratas Sprague-Dawley , Relación Estructura-Actividad , Células Vero
17.
Angew Chem Int Ed Engl ; 60(20): 11148-11152, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33629459

RESUMEN

For rare-earth separation, selective crystallization into metal-organic frameworks (MOFs) offers new opportunities. Especially important is the development of MOF platforms with high selectivity toward target ions. Here we report a MOF platform (CPM-66) with low-coordination-number environment for rare-earth ions. This platform is highly responsive to the size variation of rare-earth ions and shows exceptional ion-size selectivity during crystallization. CPM-66 family are based on M3 O trimers (M=6-coordinated Sc, In, Er-Lu) that are rare for lanthanides. We show that the size matching between urea-type solvents and metal ions is crucial for their successful synthesis. We further show that CPM-66 enables a dramatic multi-fold increase in separation efficiency over CPM-29 with 7-coordinated ions. This work provides some insights into methods to prepare low-coordinate MOFs from large ions and such MOFs could serve as high-efficiency platforms for lanthanide separation, as well as other applications.

18.
J Am Chem Soc ; 142(5): 2222-2227, 2020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-31986024

RESUMEN

An ideal material for C2H6/C2H4 separation would simultaneously have the highest C2H6 uptake capacity and the highest C2H6/C2H4 selectivity. But such material is elusive. A benchmark material for ethane-selective C2H6/C2H4 separation is peroxo-functionalized MOF-74-Fe that exhibits the best known separation performance due to its high C2H6/C2H4 selectivity (4.4), although its C2H6 uptake capacity is moderate (74.3 cm3/g). Here, we report a family of pore-space-partitioned crystalline porous materials (CPMs) with exceptional C2H6 uptake capacity and C2H6/C2H4 separation potential (i.e., C2H4 recovered from the mixture) despite their moderate C2H6/C2H4 selectivity (up to 1.75). The ethane uptake capacity as high as 166.8 cm3/g at 1 atm and 298 K, more than twice that of peroxo-MOF-74-Fe, has been achieved even though the isosteric heat of adsorption (21.9-30.4 kJ/mol) for these CPMs is as low as about one-third of that for peroxo-MOF-74-Fe (66.8 kJ/mol). While the overall C2H6/C2H4 separation potentials have not yet surpassed peroxo-MOF-74-Fe, these robust CPMs exhibit outstanding properties including high thermal stability (up to 450 °C) and aqueous stability, low regeneration energy, and a high degree of chemical and geometrical tunability within the same isoreticular framework.

19.
FASEB J ; 33(1): 1468-1481, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30161000

RESUMEN

Lysosome has a crucial role in clearance of endocytosed pathogens from the cell. Small molecules that can boost lysosome function and bactericidal ability to cope with subsequent infection are urgently needed. Here, we report that MPB, a novel berberine derivative, induced lysosome-based degradation and clearance of methicillin-resistant Staphylococcus aureus and enteroinvasive Escherichia coli in macrophages. MPB caused nuclear translocation of transcription factor EB (TFEB), which boosted expression of lysosome genes. TFEB silencing repressed the MPB-mediated enhancements in degradation and bacterial eradication. MPB switched on TFEB nuclear translocation by coupling 2 parallel signaling pathways. MPB-triggered JNK activation led to 14-3-3δ being released from TFEB, which, in turn, caused TFEB nuclear translocation. In addition, MPB induced AMPK activation and subsequent inhibition of mechanistic target of rapamycin activity, which also contributed to TFEB nuclear translocation. Importantly, genetical or pharmaceutical inhibition of TGF-ß-activated kinase 1 (TAK1) reduced MPB action remarkably. MPB acted through TAK1 at lysine 158 to activate JNK and AMPK and, thus, induced TFEB-dependent bactericidal activity in macrophages. Therefore, our study reveals a novel mechanism by which MPB controls JNK and AMPK phosphorylation cascades to activate lysosomal function and bactericidal activity via TAK1 K158-dependent manner, which may offer insight into novel therapeutic strategies to control bacterial infection.-Liu, X., Zhang, N., Liu, Y., Liu, L., Zeng, Q., Yin, M., Wang, Y., Song, D., Deng, H. MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF-ß-activated kinase 1-dependent activation of the transcription factor EB.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antibacterianos/farmacología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Berberina/análogos & derivados , Berberina/farmacología , Lisosomas/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Adenilato Quinasa/metabolismo , Animales , Núcleo Celular/metabolismo , Células Cultivadas , Humanos , MAP Quinasa Quinasa 4/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Fosforilación , Transporte de Proteínas , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
20.
Bioorg Chem ; 94: 103487, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31831161

RESUMEN

Based on the structural characteristics of aztreonam (AZN) and its target PBP3, a series of new monobactam derivatives bearing various substituents on oxime residue were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative bacteria. Among them, compounds 8p and 8r displayed moderate potency with MIC values of 0.125-32 µg/mL against most tested Gram-negative strains, comparable to AZN. Meanwhile, the combination of 8p and 8r with avibactam as a ß-lactamases inhibitor, in a ratio of 1:16, showed a promising synergistic effect against both ESBLs- and NDM-1-producing K. pneumoniae, with significantly reduced MIC values up to 8-fold and >256-fold respectively. Furthermore, both of them demonstrated excellent safety profiles both in vitro and in vivo. The results provided powerful information for further structural optimization of monobactam antibiotics to fight ß-lactamase-producing resistant Gram-negative bacteria.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Monobactamas/farmacología , Oximas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Monobactamas/síntesis química , Monobactamas/química , Oximas/química , Relación Estructura-Actividad
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