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1.
Mol Psychiatry ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844534

RESUMEN

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

2.
Phys Rev Lett ; 132(6): 065105, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38394557

RESUMEN

Stable transport of laser beams in highly overdense plasmas is of significance in the fast ignition of inertial confinement fusion, relativistic electron generation, and powerful electromagnetic emission, but hard to realize. Early in 1996, Harris proposed an electromagnetically induced transparency (EIT) mechanism, analogous to the concept in atomic physics, to transport a low-frequency (LF) laser in overdense plasmas aided by a high-frequency pump laser. However, subsequent investigations show that EIT cannot occur in real plasmas with boundaries. Here, our particle-in-cell simulations show that EIT can occur in the strongly relativistic regime and result in stable propagation of a LF laser in bounded plasmas with tens of its critical density. A relativistic three-wave coupling model is developed, and the criteria and frequency passband for EIT occurrence are presented. The passband is sufficiently wide in the strongly relativistic regime, allowing EIT to work sustainably. Nevertheless, it is narrowed to nearly an isolated point in the weakly relativistic regime, which can explain the quenching of EIT in bounded plasmas found in previous investigations.

3.
FASEB J ; 37(8): e23063, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37401890

RESUMEN

Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.


Asunto(s)
Cardiomiopatías , MicroARNs , ARN Largo no Codificante , Animales , Ratas , Apoptosis , Cardiomiopatías/metabolismo , Depresión , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/genética , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Miocitos Cardíacos/metabolismo , Piroptosis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
4.
FASEB J ; 37(4): e22866, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36929614

RESUMEN

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Canales de Potasio de Gran Conductancia Activados por el Calcio , Ratones , Animales , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/genética , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Homeostasis
5.
Arch Microbiol ; 206(4): 141, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38441685

RESUMEN

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).


Asunto(s)
Bacterias , Ácido Succínico , Anaerobiosis , Filogenia , Succinatos , ADN
6.
Pharmacol Res ; 203: 107182, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614373

RESUMEN

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.


Asunto(s)
Epigénesis Genética , Inflamación , Procesamiento Proteico-Postraduccional , Piroptosis , Humanos , Piroptosis/efectos de los fármacos , Animales , Inflamación/genética , Inflamación/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología
7.
BMC Vet Res ; 20(1): 203, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755641

RESUMEN

BACKGROUND: Avian influenza virus (AIV) not only causes huge economic losses to the poultry industry, but also threatens human health. Reverse transcription recombinase-aided amplification (RT-RAA) is a novel isothermal nucleic acid amplification technology. This study aimed to improve the detection efficiency of H5, H7, and H9 subtypes of AIV and detect the disease in time. This study established RT-RAA-LFD and real-time fluorescence RT-RAA (RF-RT-RAA) detection methods, which combined RT-RAA with lateral flow dipstick (LFD) and exo probe respectively, while primers and probes were designed based on the reaction principle of RT-RAA. RESULTS: The results showed that RT-RAA-LFD could specifically amplify H5, H7, and H9 subtypes of AIV at 37 °C, 18 min, 39 °C, 20 min, and 38 °C, 18 min, respectively. The sensitivity of all three subtypes for RT-RAA-LFD was 102 copies/µL, which was 10 ∼100 times higher than that of reverse transcription polymerase chain reaction (RT-PCR) agarose electrophoresis method. RF-RT-RAA could specifically amplify H5, H7, and H9 subtypes of AIV at 40 °C, 20 min, 38 °C, 16 min, and 39 °C, 17 min, respectively. The sensitivity of all three subtypes for RF-RT-RAA was 101 copies/µL, which was consistent with the results of real-time fluorescence quantification RT-PCR, and 100 ∼1000 times higher than that of RT-PCR-agarose electrophoresis method. The total coincidence rate of the two methods and RT-PCR-agarose electrophoresis in the detection of clinical samples was higher than 95%. CONCLUSIONS: RT-RAA-LFD and RF-RT-RAA were successfully established in this experiment, with quick response, simple operation, strong specificity, high sensitivity, good repeatability, and stability. They are suitable for the early and rapid diagnosis of Avian influenza and they have positive significance for the prevention, control of the disease, and public health safety.


Asunto(s)
Pollos , Virus de la Influenza A , Gripe Aviar , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Transcripción Reversa , Animales , Gripe Aviar/virología , Gripe Aviar/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/veterinaria , Técnicas de Amplificación de Ácido Nucleico/métodos , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Recombinasas/metabolismo , Sensibilidad y Especificidad , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/diagnóstico
8.
J Environ Manage ; 359: 120996, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38669885

RESUMEN

Enhalus acoroides, the largest seagrass species in terms of morphology, has been observed to be declining significantly. In an effort to restore seagrass meadows, we conducted a transplantion utilizing dislodged rhizome fragments of E. acoroides as the donor materials. The growth of transplanted seagrass was monitored over a period of three years, and the impact of seagrass recolonization on sedimentary environment was assessed through analysis of sediment microbial diversity. The transplanted plants displayed notable growth, resulting in the successful recolonization of experimental plots by seagrass. The 3-year data also revealed the following findings: 1) the new shoot recruitment rate (per year) (NSR) of transplanted seagrass was 2.33 in the first year, 1.36 in the second year, and 0.83 in the third year, indicating a rapid initial growth rate of E. acoroides that subsequently slowed down; 2) the numbers of shoots and aboveground biomass of transplanted seagrass had increased by 13.0 and 15.9-fold, respectively, whereas only 3.3 and 5.3-fold increases of the natural seagrass were observed, suggesting that the transplantation of seagrass leads to a significantly accelerated recovery compared to its natural regeneration process. Furthermore, the restoration of E. acoroides resulted in a higher microbial diversity in the submarine sediments within the restoration area, as compared to the adjacent unvegetated area. This suggests that the re-vegetation of E. acoroides has a positive influence on the overall health of the sedimentary environment. This study strongly advocates for the active transplantation of dislodged E. acoroides plants resulting from human activities as a potential approach for future coastal management, specifically for the restoration of E. acoroides meadows.


Asunto(s)
Sedimentos Geológicos , Rizoma , Sedimentos Geológicos/microbiología , Biodiversidad , Biomasa
9.
J Anesth ; 38(2): 206-214, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38267728

RESUMEN

PURPOSE: The study aimed to investigate potential risk factors for emergence delirium (ED) in pediatric patients after tonsillectomy and adenoidectomy (T&A). METHODS: This prospective, single-center observational study enrolled children aged 3-7 years who underwent T&A under general anesthesia. ED was assessed according to DSM-IV or V criteria. Receiver operating characteristic curve analysis was performed to evaluate the predicative and cut-off values of risk factors, including age, preoperative anxiety level, postoperative pain and neutrophil-lymphocyte ratio (NLR) for ED. Univariate and multivariate logistic regression analyses were performed to investigate risk factors for ED. RESULTS: 94 pediatric patients who underwent T&A were enrolled and 19 developed ED (an incidence of 25.3%). Receiver operating characteristic analysis indicated that preoperative NLR was a significant predictor of ED with a cut-off value of 0.8719 and an area under the curve (AUC) of 0.671 (95% confidence interval (CI) 0.546-0.796, P = 0.022). Preoperative NLR (< 0.8719) and postoperative pain were independent risk factors associated with ED (odds ratio: 0.168, 95% CI 0.033-0.858, P = 0.032; odds ratio: 7.298, 95% CI 1.563-34.083, P = 0.011) according to multivariate logistic regression analysis. CONCLUSIONS: Preoperative NLR level and postoperative pain were independent risk factors for ED in pediatric patients undergoing T&A.


Asunto(s)
Delirio del Despertar , Tonsilectomía , Humanos , Niño , Delirio del Despertar/epidemiología , Delirio del Despertar/etiología , Tonsilectomía/efectos adversos , Adenoidectomía/efectos adversos , Estudios Prospectivos , Neutrófilos , Linfocitos , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología
10.
Chin J Traumatol ; 27(2): 114-120, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37311687

RESUMEN

PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia , Preservación de Órganos , Animales , Perros , Temperatura , Preservación de Órganos/métodos , Perfusión/métodos , Extremidad Superior , Miembro Anterior , Aumento de Peso , Hígado
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 403-409, 2024 Apr 15.
Artículo en Zh | MEDLINE | ID: mdl-38660905

RESUMEN

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.


Asunto(s)
Altitud , Encéfalo , Electroencefalografía , Oxígeno , Humanos , Recién Nacido , Encéfalo/metabolismo , Oxígeno/metabolismo , Espectroscopía Infrarroja Corta , Estudios Prospectivos
12.
Mol Med ; 29(1): 93, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37415097

RESUMEN

The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.


Asunto(s)
Diabetes Mellitus Tipo 2 , Glucosa , Humanos , Metabolismo de los Lípidos , Procesamiento Proteico-Postraduccional , Fosforilación , Proteínas
13.
Small ; 19(33): e2301364, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37086107

RESUMEN

Construction of ferroelectric and optimization of macroscopic polarization has attracted tremendous attention for next generation light weight and flexible devices, which brings fundamental vitality for molecular ferroelectrics. However, effective molecular tailoring toward cations makes ferroelectric synthesis and modification relatively elaborate. Here, the study proposes a facile method to realize triggering and optimization of ferroelectricity. The experimental and theoretical investigation reveals that orientation and alignment of polar cations, dominated factors in molecular ferroelectrics, can be controlled by easily processed anionic modification. In one respect, ferroelectricity is induced by strengthened intermolecular interaction. Moreover, ≈50% of microscopic polarization enhancement (from 8.07 to 11.68 µC cm-2 ) and doubling of equivalent polarization direction (from 4 to 8) are realized in resultant ferroelectric FEtQ2ZnBrI3 (FEQZBI, FEtQ = N-fluoroethyl-quinuclidine). The work offers a totally novel platform for control of ferroelectricity in organic-inorganic hybrid ferroelectrics and a deep insight of structure-property correlations.

14.
Plant Cell Environ ; 46(9): 2841-2850, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37332130

RESUMEN

Hypoxia is a major emerging threat to coastal ecosystems, which is closely related to the decline in seagrass meadows, but its damage mechanism is still unclear. This study found that hypoxia at night significantly reduced the photosynthetic capacity of Enhalus acoroides after reillumination. Photosystem II (PSII) was damaged by high-light stress during daytime low-tide exposure, but high-light-damaged PSII of E. acoroides could recover part of its activity indark normoxic seawater to maintain the normal operation of photosynthesis after reillumination during the next day. However, hypoxia inhibited the recovery of damaged PSII under darkness. By transcriptomic analysis and inhibitor verification experiments, dark hypoxia was shown to inhibit respiration, thereby reducing ATP production and preventing ATP from being transported into chloroplasts, which, in turn, led to an insufficient supply of energy required for PSII to recover. This study demonstrated that hypoxia has several negative impacts on the photosynthetic apparatus of E. acoroides at night reducing photosynthetic capacity after reillumination, which may be an important factor leading to the decline of the seagrass meadows.


Asunto(s)
Ecosistema , Fotosíntesis , Complejo de Proteína del Fotosistema II/metabolismo , Hipoxia , Adenosina Trifosfato
15.
Mol Psychiatry ; 27(11): 4510-4525, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36056172

RESUMEN

Depression and anxiety are major global health burdens. Although SSRIs targeting the serotonergic system are prescribed over 200 million times annually, they have variable therapeutic efficacy and side effects, and mechanisms of action remain incompletely understood. Here, we comprehensively characterise the molecular landscape of gene regulatory changes associated with fluoxetine, a widely-used SSRI. We performed multimodal analysis of SSRI response in 27 mammalian brain regions using 310 bulk RNA-seq and H3K27ac ChIP-seq datasets, followed by in-depth characterisation of two hippocampal regions using single-cell RNA-seq (20 datasets). Remarkably, fluoxetine induced profound region-specific shifts in gene expression and chromatin state, including in the nucleus accumbens shell, locus coeruleus and septal areas, as well as in more well-studied regions such as the raphe and hippocampal dentate gyrus. Expression changes were strongly enriched at GWAS loci for depression and antidepressant drug response, stressing the relevance to human phenotypes. We observed differential expression at dozens of signalling receptors and pathways, many of which are previously unknown. Single-cell analysis revealed stark differences in fluoxetine response between the dorsal and ventral hippocampal dentate gyri, particularly in oligodendrocytes, mossy cells and inhibitory neurons. Across diverse brain regions, integrative omics analysis consistently suggested increased energy metabolism via oxidative phosphorylation and mitochondrial changes, which we corroborated in vitro; this may thus constitute a shared mechanism of action of fluoxetine. Similarly, we observed pervasive chromatin remodelling signatures across the brain. Our study reveals unexpected regional and cell type-specific heterogeneity in SSRI action, highlights under-studied brain regions that may play a major role in antidepressant response, and provides a rich resource of candidate cell types, genes, gene regulatory elements and pathways for mechanistic analysis and identifying new therapeutic targets for depression and anxiety.


Asunto(s)
Ensamble y Desensamble de Cromatina , Fluoxetina , Humanos , Antidepresivos/farmacología , Encéfalo/metabolismo , Metabolismo Energético/genética , Fluoxetina/farmacología , Fluoxetina/metabolismo , Mamíferos , Multiómica , Animales
16.
Prev Med ; 174: 107648, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37507026

RESUMEN

To evaluate the effectiveness of a self-designed pressure-guided fracture positioning device, a prospective study was conducted in patients with posterior ankle fractures undergoing surgery using the device. Twenty-seven cases of ankle joint fracture with posterior malleolus fracture were treated by surgery. In the process of fixing posterior malleolus fracture, a self-designed fracture positioning compression guide device was used to fix posterior malleolus bone by anterior and posterior approaches. Postoperative CT images were used to assess the fixation position as well as length of the screw and the compression of the fracture. All patients had healed ankle fractures, and the anterior-posterior screws were fixed in the central area of the posterior malleolus. Posterior malleolus fragment displacement was <2 mm. The screw effectively secured the cortex beyond the length of the posterior malleolus cortex by no more than two threads. The good rate of ankle joint function was 85.16%. Compared to traditional surgical techniques, minimally invasive fixation using the self-designed positioning compression guide device has several advantages, including smaller trauma, faster postoperative recovery, and improved patient satisfaction. The device also provides the surgeon with greater control and precision during the surgical procedure, which can contribute to better surgical outcomes.


Asunto(s)
Fracturas de Tobillo , Humanos , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Estudios Prospectivos , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Articulación del Tobillo/cirugía , Estudios Retrospectivos
17.
Phys Chem Chem Phys ; 25(45): 30934-30948, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37937400

RESUMEN

High-performance thermoelectric materials in theoretical and experimental research are mostly composed of expensive, scarce, heavy elements and rarely of single light elements, which severely limit their application and development. Based on density functional and semiclassical Boltzmann transport theory, we determine that a stable phosphorene allotrope, named Tri-Tri phosphorene, has super-high electron mobility (23845.29 cm2 V-1 s-1) much higher than those of most two-dimension materials. Moreover, its optimized maximum ZT can reach up to 3.43 at room temperature (4.83 at 500 K and 5.92 at 700 K), exhibiting highly favorable prospects in practical thermoelectric systems. Motivated by the excellent properties of Tri-Tri phosphorene, we further demonstrate the structural stability of Tri-Tri arsenene and Tri-Tri antimonene and predict that the two Tri-Tri structures also have high Seebeck coefficients and electron mobilities. Their lattice thermal conductivities are dramatically decreased compared with Tri-Tri phosphorene. Thus, their predicted thermoelectric performances are also excellent, with maximum ZT values of 4.12 (Tri-Tri arsenene) and 3.54 (Tri-Tri antimonene) at room temperature. The low layer moduli of the three Tri-Tri structures indicate that they have high mechanical flexibility and suitability for current device assemblies. All these desirable properties make Tri-Tri group-VA materials promising for future applications in thermoelectric devices.

18.
Appl Opt ; 62(24): 6464-6471, 2023 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-37706840

RESUMEN

A high-power near-infrared wavelength-modulated differential photoacoustic spectroscopy sensor for parts-per-billion (ppb) level methane detection is reported by using a homemade Raman fiber optical amplifier. A commercial 1653.7 nm continuous wave distributed feedback laser is employed as a seed source to excite a high light power of ∼550m W, which greatly improves sensor performance. Wavelength modulation spectroscopy and differential techniques are applied to further improve the signal-to-noise ratio of the photoacoustic signal. A 1σ minimum detection limit of ∼10p p b for methane detection is achieved with an integration time of 10 s.

19.
Molecules ; 28(15)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37570900

RESUMEN

Propane catalytic oxidation is an important industrial chemical process. However, poor activity is frequently observed for stable C-H bonds, especially for non-noble catalysts in low temperature. Herein, we reported a controlled synthesis of catalyst Co3O4@CeO2-IE via inverse loading and proposed a strategy of oxygen vacancy for its high catalytic oxidation activity, achieving better performance than traditional supported catalyst Co3O4/CeO2-IM, i.e., the T50 (temperature at 50% propane conversion) of 217 °C vs. 235 °C and T90 (temperature at 90% propane conversion) of 268 °C vs. 348 °C at the propane space velocity of 60,000 mL g-1 h-1. Further investigations indicate that there are more enriched oxygen vacancies in Co3O4@CeO2-IE due to the unique preparation method. This work provides an element doping strategy to effectively boost the propane catalytic oxidation performance as well as a bright outlook for efficient environmental catalysts.

20.
Zhongguo Zhong Yao Za Zhi ; 48(1): 170-182, 2023 Jan.
Artículo en Zh | MEDLINE | ID: mdl-36725269

RESUMEN

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.


Asunto(s)
Medicamentos Herbarios Chinos , Factor de Necrosis Tumoral alfa , Ácido Clorogénico , Medicamentos Herbarios Chinos/farmacología , Ácido gamma-Aminobutírico , Interleucina-6 , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Factor de Necrosis Tumoral alfa/genética , Animales , Ratones , Células RAW 264.7
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