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1.
J Agric Food Chem ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814711

RESUMEN

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.

2.
Acta Pharmacol Sin ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789495

RESUMEN

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

3.
Sci Rep ; 14(1): 9461, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658587

RESUMEN

Average windward area is an important index for calculating the trajectory, velocity attenuation and terminal effect of explosive fragments. In order to solve the problems that existing theoretical method cannot calculate windward area of irregular fragment and experiment method is not convenient for automatic calculation and has low accuracy, a Monte Carlo subdivision projection simulation algorithm is proposed. The average windward area of arbitrary shaped fragments can be obtained with coordinate translation, random rotation, plane projection, convex-hull triangulation, concave boundary searching and sorting with maximum edge length constraint, subdivision area calculation, and averaging by thousands of cycles. Results show that projection area obtained by the subdivision projection algorithm is basically the same as that obtained by software method of computer aided design. Moreover, the maximum calculation error of the algorithm is less than 7%, and its accuracy is much higher than that of the equivalent ellipsoid method. The average windward area calculated by the Monte Carlo subdivision projection simulation algorithm is consistent with theoretical formula for prefabricated fragments, and the error is less than 3%. The convergence and accuracy of the Monte Carlo subdivision projection algorithm are better than those of the icosahedral uniform orientation method.

4.
Clin Transl Sci ; 17(4): e13787, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38558535

RESUMEN

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.


Asunto(s)
Anticoagulantes , Coagulación Sanguínea , Adulto , Humanos , Tiempo de Tromboplastina Parcial , Voluntarios Sanos , China , Método Doble Ciego , Relación Dosis-Respuesta a Droga
5.
Acta Pharmacol Sin ; 45(5): 926-944, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38286832

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.


Asunto(s)
Esclerosis Amiotrófica Lateral , Astrocitos , Loratadina , Loratadina/análogos & derivados , Ratones Transgénicos , Médula Espinal , Superóxido Dismutasa-1 , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Médula Espinal/metabolismo , Ratones , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Loratadina/farmacología , Loratadina/uso terapéutico , Humanos , Receptor de Serotonina 5-HT2A/metabolismo , Modelos Animales de Enfermedad , Masculino , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Ratones Endogámicos C57BL
6.
Acta Pharmacol Sin ; 44(12): 2388-2403, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37580494

RESUMEN

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.


Asunto(s)
Diabetes Mellitus Experimental , Neuropatías Diabéticas , Vincamina , Animales , Ratones , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/patología , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Monoterpenos/química , Monoterpenos/farmacología , Receptores Acoplados a Proteínas G , Nervio Ciático/patología , Transducción de Señal , Vincamina/farmacología , Vincamina/uso terapéutico
7.
Basic Clin Pharmacol Toxicol ; 133(5): 592-602, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37635270

RESUMEN

Drugs for acute postoperative pain and breakthrough cancer pain are still urgent in clinical. LPM3480392 is a G-protein-biased ligand at the µ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics and pharmacodynamics under single ascending doses (Study I 0.1-3.0 mg, 30 min) and different infusion times (Study II, 0.6-1.0 mg, 2-15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (Cmax ) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at a dose of 0.6 mg under a 2 min infusion rate elicited effective analgesia as the peak effect within 10-30 min, which was measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.

8.
Huan Jing Ke Xue ; 44(7): 3872-3880, 2023 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-37438286

RESUMEN

In order to explore the impact of different anthropogenic disturbances on the ecological environment of natural rivers, the bacterial community in the channel sediments of the Jialing River was taken as the research object, and the high-throughput sequencing technique was used to analyze the community composition and functional changes of bacteria in the channel sediments of rivers with engineering disturbance, tributary disturbance, sand mining disturbance, reclamation disturbance, and undisturbed section. The results showed that there were significant differences in the physical and chemical properties of channel sediments and bacterial community diversity in different disturbance sections of the Jialing River (P<0.05). The undisturbed section had the highest bacterial community diversity, whereas the sand mining disturbance and undisturbed section had the highest bacterial community uniformity, and tributary disturbance and reclamation disturbance both resulted in a decrease in bacterial community diversity and uniformity. The effect of engineering disturbance on bacterial community composition was significantly different from that of the other four disturbance sections. The dominant bacterial phyla were Proteobacteria, Actinobacteriota, Acidobacteriota, and Chloroflexi, and the dominant bacterial classes were γ-Proteobacteria, α-Proteobacteria, and Vicinamibacteria. Sand mining disturbance led to the increase in Actinobacteria, and engineering disturbance promoted the increase in Acidobacteria. Moisture content, total organic carbon, total nitrogen, and total phosphorus were the main environmental factors affecting the changes in sediment microbial communities. The bacterial communities mainly involved four categories of primary metabolic functions, including metabolism, genetic information processing, environmental information processing, and cellular processes, and 18 categories of secondary metabolic functions, such as global and overview maps, carbohydrate metabolism, amino acid metabolism, cofactor and vitamin metabolism, and energy metabolism. Human interference led to significant changes in energy metabolism, cofactor and vitamin metabolism, nucleotide metabolism, replication and repair, and translation (P<0.05). In conclusion, anthropogenic disturbance led to the mutation of bacterial community diversity and function, which destroyed the stability of the microbial community structure in Jialing River sediments.


Asunto(s)
Ríos , Arena , Humanos , Bacterias/genética , Acidobacteria , Vitaminas
9.
Front Chem ; 10: 860398, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35433628

RESUMEN

New multilayer 3D chiral molecules have been designed and synthesized asymmetrically through the strategy of center-to-multilayer folding chirality control and double Suzuki couplings. Individual diastereoisomers were readily obtained and separated via flash column chromatography. The key diastereoisomer was further converted into corresponding enantiomers. These enantiomers possess electron-deficient aromatic bridges layered with top and bottom aromatic scaffolds. X-ray structural analysis has unambiguously confirmed the configuration, and intermolecular packing results in regular planar patterns in solid crystals. The synthesis was achieved in a total of ten steps starting from commercially available starting materials.

10.
Acta Pharmacol Sin ; 43(9): 2226-2241, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35091686

RESUMEN

Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERß is largely distributed in the hippocampus and cardiovascular system, suggesting that ERß selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERß agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg-1 · d-1, i.g.) for 90 days. We first demonstrated that PTA bound to ERß with a dissociation constant (KD) of 288.9 ± 35.14 nM in microscale thermophoresis. Then we showed that PTA administration dose-dependently ameliorated cognitive defects evaluated in Morris water maze and Y-maze testes. Furthermore, PTA administration reduced amyloid plaque deposition in the hippocampus by promoting microglial phagocytosis; PTA administration improved synaptic integrity through enhancing BDNF/TrkB/CREB signaling, ameliorated oxidative stress by Catalase level, and regulated Bcl-2 family proteins in the hippocampus. The therapeutic effects of PTA were also observed in vitro: PTA (5, 10, 20 µM) dose-dependently increased phagocytosis of o-FAM-Aß42 in primary microglia and BV2 cells through enhancing ERß/TLR4 signaling; PTA treatment ameliorated o-Aß25-35-induced reduction of synapse-related proteins VAMP2 and PSD95 in primary neurons through enhancing ERß/BDNF/TrkB/CREB pathways; PTA treatment alleviated o-Aß25-35-induced oxidative stress in primary neurons through targeting ERß and increasing Catalase expression. Together, this study has addressed the efficacy of selective ERß agonist in the amelioration of AD and highlighted the potential of PTA as a drug lead compound against the disease.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Catalasa/metabolismo , Modelos Animales de Enfermedad , Receptor beta de Estrógeno/metabolismo , Estrógenos/metabolismo , Femenino , Hipocampo/metabolismo , Ratones , Ratones Transgénicos , Placa Amiloide/tratamiento farmacológico , Presenilina-1 , Sesquiterpenos
11.
Chemistry ; 27(30): 7977, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33931916

RESUMEN

Invited for the cover of this issue is Guigen Li and co-workers at Texas Tech University and Nanjing University. The cover artwork shows that chirality phenomena exists in the universe and in nature, including at micro and molecular levels. Read the full text of the article at 10.1002/chem.202100700.

12.
BMC Infect Dis ; 21(1): 336, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33838648

RESUMEN

BACKGROUND: Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB). An estimated 1.7 billion people worldwide are infected with Mycobacterium tuberculosis (LTBI) during the incubation period without any obvious symptoms. Because of MTB's high infection and mortality rates, there is an urgent need to develop a fast, portable, and sensitive diagnostic technology for its detection. METHODS: We included research from PubMed, Cochrane Library, Web of Science, and Embase and extracted the data. MetaDisc and STATA were used to build forest plots, Deek's funnel plot, Fagan plot, and bivariate boxplot for analysis. RESULTS: Forty-six articles were analyzed, the results of which are as follows: sensitivity and specificity were 0.92 (0.91-0.93) and 0.95 (0.94-0.95) respectively. The NLR and PLR were 0.04 (95% CI 0.03-0.07) and 25.32 (95% CI 12.38-51.78) respectively. DOR was 639.60 (243.04-1683.18). The area under the SROC curve (AUC) was 0.99. CONCLUSIONS: MPT64 exhibits good diagnostic efficiency for MTB. There is no obvious heterogeneity between the three commercial kits.


Asunto(s)
Antígenos Bacterianos/inmunología , Mycobacterium tuberculosis , Juego de Reactivos para Diagnóstico , Tuberculosis/microbiología , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Inmunoensayo/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Sensibilidad y Especificidad , Tuberculosis/diagnóstico
13.
Chemistry ; 27(30): 8013-8020, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33830589

RESUMEN

The first asymmetric catalytic approach to multilayer 3D chirality has been achieved by using Suzuki-Miyaura cross-couplings. New chiral catalysts were designed and screened under various catalytic systems that proved chiral amide-phosphines to be more efficient ligands than other candidates. The multilayer 3D framework was unambiguously determined by X-ray structural analysis showing a parallel pattern of three layers consisting of top, middle and bottom aromatic rings. The X-ray structure of a catalyst complex, dichloride complex of Pd-phosphine amide, was obtained revealing an interesting asymmetric environment nearby the Pd metal center. Three rings of multilayer 3D products can be readily changed by varying aromatic ring-anchored starting materials. The resulting multilayer products displayed strong luminescence under UV irradiation and strong aggregation-induced emission (AIE). In the future, this work would benefit not only the field of asymmetric synthesis but also materials science, in particular polarized organic electronics, optoelectronics and photovoltaics.

14.
Neurosci Lett ; 742: 135515, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33227370

RESUMEN

Bipolar disorder (BD) is a debilitating mental disorder with complex clinical manifestations and low diagnostic accuracy. Depressive episodes are most common in the course of BD with high comorbidity and suicide rates, which present greater clinical challenges than mania and hypomania episodes. However, there are no objective biomarkers for bipolar depression. The aim of this study was to detect urinary metabolite biomarkers that could be useful for the diagnosis of bipolar depression. Nuclear magnetic resonance spectroscopy was used to profile urine samples of patients with bipolar depression (n = 37) and healthy volunteers (n = 48). Data were analyzed using Orthogonal Partial Least Square Discriminant Analysis and t-test. Differential metabolites were identified (VIP > 1 and p < 0.05), and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways. In total, we identified seven metabolites differentially expressed in patients with BD and healthy controls. Compared with healthy group, the levels of betaine, glycerol, hippuric acid, indole sulfate, trimethylamine oxide, and urea in urine samples of BD patients were significantly higher, while the level of inositol was significantly lower. Most of these small molecules are related to lipid metabolism and gut microbiota metabolism. These differential metabolites could provide critical insight into the pathological mechanisms of bipolar depression. The results of this study provide a meaningful reference for similar and further studies in the future.


Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Bipolar/orina , Metabolómica/métodos , Resonancia Magnética Nuclear Biomolecular/métodos , Adolescente , Adulto , Betaína/orina , Biomarcadores/metabolismo , Biomarcadores/orina , Femenino , Hipuratos/orina , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
15.
Environ Res ; 190: 109982, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32745749

RESUMEN

Waterborne pathogens and their associated diseases are major threats to public health, and surveillance of pathogens and identification of the sources of pollution are imperative for preventing infections. However, simultaneously quantitative detection of multiple pathogens and pollution sources in water environments is the major challenge. In this study, we developed and validated a highly sensitive (mostly >80%) and highly specific (>99%) high-throughput quantitative PCR (HT-qPCR) approach, which could simultaneously quantify 68 marker genes of 33 human pathogens and 23 fecal markers of 10 hosts. The HT-qPCR approach was then successfully used to investigate pathogens and fecal pollution in marine recreational water samples of Xiamen, China. Totally, seven pathogenic marker genes were found in 13 beach bathing waters, which targeted Acanthamoeba spp., Clostridium perfringens, enteropathogenic Escherichia coli, Klebsiella pneumoniae, Vibrio cholera/V. parahaemolyticus and Legionella spp.. Fecal markers from human and dog were the most frequently detected, indicating human and dog feces were the main contamination in the recreational waters. Nanopore sequencing of full-length 16S rRNA gene revealed that 28 potential human pathogens were detected and electrical conductivity, salinity, oxidation-reduction potential and dissolved oxygen were significantly correlated with the variation in bacterial community. Our results demonstrated that HT-qPCR approach had the potential rapid quantification of microbial contamination, providing useful data for assessment of microbial pathogen associated health risk and development of management practices to protect human health.


Asunto(s)
Playas , Microbiología del Agua , Animales , China , Perros , Monitoreo del Ambiente , Heces , Humanos , ARN Ribosómico 16S/genética , Agua , Contaminación del Agua/análisis
16.
Ying Yong Sheng Tai Xue Bao ; 31(2): 474-482, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32476340

RESUMEN

Maize stalk mulching is a conservation tillage method that has been currently promoted in northeastern China Plain. Remote sensing estimation of regional crop residue cover (CRC) can quickly obtain the information of straw mulching in a large area, which plays an important role in monitoring and popularizing the work of straw mulching. In this study, the normalized difference til-lage index (NDTI), simple tillage index (STI), normalized difference residue index (NDRI), and normalized difference index 7 (NDI7) were extracted from Sentinel-2A image and used to establish a linear regression model for CRC and spectral indices in Lishu County of Jilin Province. The results showed that soils had strong spatial heterogeneity in the study area, which would lead to a significant impact on the spectral index regression model. Using soil texture classification (zoning) to establish regression model could improve the inversion accuracy. Soil spatial heterogeneity would increase the estimation error of the model. The four spectral indices had a strong correlation with CRC, among which the NDTI and STI models performed better. The zonal linear regression model based on NDTI and STI verified that R2 was 0.84 and RMSE was 13.3%, which was better than the non-zonal model (R2 was 0.75 and RMSE was 16.5%) and thus effectively improved the inversion accuracy.


Asunto(s)
Suelo , Zea mays , China , Tecnología de Sensores Remotos
17.
ACS Appl Mater Interfaces ; 12(13): 15573-15578, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32155041

RESUMEN

The coordination interactions between transition-metal ions (Cu2+, Ag+) and sulfur atoms on ultrathin two-dimensional (2D) nanosheets of spin-crossover (SCO) metal-organic frameworks {[Fe(1,3-bpp)2(NCS)2]2}n (1,3-bpp = 1,3-di(4-pyridyl)propane), which constructed the ultrathin 2D nanosheets into three-dimensional (3D) nanoparticles, have made a profound effect on the SCO performance. Compared with 2D nanosheets, both the intraligand π-π* transition band and the metal-to-ligand charge transition band from the d(Fe) + π(NCS) to π*(1,3-bpp), for the 3D nanoparticles, have shown dramatic blue-shifts; meanwhile, the d-d transition band for the high-spin (HS) state Fe(II) ions has been generated, suggesting significantly the influence of 3D assemble-caused dimensional changes on the solid-state SCO performance of ultrathin 2D nanosheets. More importantly, by loading on the ytterbium ion (Yb3+)-sensitized hexagonal phase upconverting nanoparticles in the aqueous colloidal suspension, the near infrared (NIR) light (980 nm) triggered HS (high spin) to LS (low spin) state transitions have been observed, demonstrating the achievement of challenging target of NIR light-triggered molecular conversion under environment conditions.

18.
Int J Biol Macromol ; 151: 376-383, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32084467

RESUMEN

Natural products belonging to a class of generally-recognized-as-safe biomaterials have exceptional biocompatibility and biodegradability and can be used as delivery vehicles for a variety of functional foods. Adlay (Coix lacryma-jobi), is a nutritious food, rich in various bioactive ingredients. Coix seed oil extract (CSO) is also bioactive but it is sensitive to oxidation. In this study, a bioactive delivery system based on homologous polysaccharides and proteins was developed to deliver coix seed oil. The results show that the CSO nanoparticles have high encapsulation efficiency, narrow particle size distribution, and good stability. Moreover, the fusion of the nanoparticles with the membrane enabled the transport of CSO through the Caco-2 cell monolayer and improved the intestinal permeability. These findings could provide useful information for designing homologous polysaccharide and protein-based delivery systems to increase the bioavailability of lipophilic nutraceuticals in the food industry.


Asunto(s)
Coix/química , Aceites de Plantas/química , Polisacáridos/química , Proteínas/química , Semillas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Humanos , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Aceites de Plantas/farmacología , Polisacáridos/farmacología
19.
Chemosphere ; 242: 125207, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31675591

RESUMEN

Landfills leachate contained diverse antibiotic resistance genes (ARGs). Treated landfill leachate effluent could enter into the downstream environments, leading to the dissemination of ARGs, which might pose a health risk to public. Here, we used high-throughput qPCR to characterize the resistome and 16S rRNA-based Illumina sequencing to analyze the bacterial community in a leachate treatment plant and the river near the landfill. A total of 91 ARGs and 5 mobile genetic elements were detected. Leachate treatment process significantly changed the profiles of resistome and bacterial community structures. Similar bacterial community structure and ARG profiles were detected between effluent and downstream river, which were both dominated by multidrug and beta-lactams resistance genes and harbored higher ARG relative abundance than that in upstream river. In particular, seven ARGs were detected both in effluent and downstream river samples but not detected in upstream river, including genes encoding resistance to vancomycin (vanXD and vanSB) and carbapenem (cphA and blaGES), which implied the effects of the effluent on its receiving river. This study highlights the risk of discharge of processed landfill leachate in dissemination of antibiotic resistance determinants to the environments, and suggests an urgent need for surveillance of ARGs and development of techniques to mitigate the risk.


Asunto(s)
Farmacorresistencia Microbiana/genética , Contaminantes Químicos del Agua/análisis , Antibacterianos/análisis , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/genética , Farmacorresistencia Microbiana/efectos de los fármacos , Genes Bacterianos , ARN Ribosómico 16S/genética , Ríos/microbiología , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/farmacología
20.
Rev Sci Instrum ; 90(8): 085104, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31472658

RESUMEN

On the basis of the actively controlled multiple-fan wind tunnel we designed, this paper proposes a latticed mode-based control strategy for the fan array. The so-called latticed mode is the overall topology of the working fans. In order to investigate the simulation ability of the latticed mode, several latticed modes are designed to analyze the temporal and spatial properties of generated wind fields. Airflow data under different latticed modes are measured using nine two-dimensional anemometers, and then, statistical indicators of wind speed and wind direction, as well as the spatial uniformity and complexity of generated wind fields, are calculated to analyze the characteristics of wind records. The results indicate that the distribution of active fans in the latticed mode has significant influence on the statistical properties and spatial evolutions of wind speed and direction. Besides, the latticed modes can regulate the spatial uniformity and complexity of the wind fields. The latticed modes with a high clustering degree of active fans can generate wind fields with low spatial uniformity and high complexity. In addition to the fan voltage and the rotation angle of swivel plates, the proposed latticed mode provides more possibilities for wind field simulation.

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