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1.
PLoS Comput Biol ; 20(9): e1012415, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39226309

RESUMO

Revealing the relationship between neural network structure and function is one central theme of neuroscience. In the context of working memory (WM), anatomical data suggested that the topological structure of microcircuits within WM gradient network may differ, and the impact of such structural heterogeneity on WM activity remains unknown. Here, we proposed a spiking neural network model that can replicate the fundamental characteristics of WM: delay-period neural activity involves association cortex but not sensory cortex. First, experimentally observed receptor expression gradient along the WM gradient network is reproduced by our network model. Second, by analyzing the correlation between different local structures and duration of WM activity, we demonstrated that small-worldness, excitation-inhibition balance, and cycle structures play crucial roles in sustaining WM-related activity. To elucidate the relationship between the structure and functionality of neural networks, structural circuit gradients in brain should also be subject to further measurement. Finally, combining anatomical data, we simulated the duration of WM activity across different brain regions, its maintenance relies on the interaction between local and distributed networks. Overall, network structural gradient and interaction between local and distributed networks are of great significance for WM.


Assuntos
Memória de Curto Prazo , Modelos Neurológicos , Rede Nervosa , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiologia , Humanos , Biologia Computacional , Animais , Encéfalo/fisiologia , Simulação por Computador , Neurônios/fisiologia , Potenciais de Ação/fisiologia
2.
ACS Nano ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238258

RESUMO

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

3.
World J Clin Cases ; 12(25): 5832-5838, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39247735

RESUMO

BACKGROUND: Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi (O. tsutsugamushi). Omadacycline, a novel tetracycline, exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens. However, omadacycline application in the treatment of scrub typhus remains limited. CASE SUMMARY: In the present work, we report several cases of scrub typhus, with the main clinical symptoms being fever, the formation of eschars or ulcers, local or systemic lymphadenopathy, headache, myalgia and rash. Blood samples were collected before omadacycline was administered, and O. tsutsugamushi infection was confirmed through targeted next-generation sequencing (tNGS). After two days of treatment, the patients' symptoms, including fever, were alleviated, with no adverse drug reactions. CONCLUSION: tNGS is an effective method for diagnosing scrub typhus. Omadacycline can be considered an alternative option for antiinfective therapy in patients with O. tsutsugamushi infections.

4.
Cogn Neurodyn ; 18(4): 1989-2001, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39104681

RESUMO

The functional neurons are basic building blocks of the nervous system and are responsible for transmitting information between different parts of the body. However, it is less known about the interaction between the neuron and the field. In this work, we propose a novel functional neuron by introducing a flux-controlled memristor into the FitzHugh-Nagumo neuron model, and the field effect is estimated by the memristor. We investigate the dynamics and energy characteristics of the neuron, and the stochastic resonance is also considered by applying the additive Gaussian noise. The intrinsic energy of the neuron is enlarged after introducing the memristor. Moreover, the energy of the periodic oscillation is larger than that of the adjacent chaotic oscillation with the changing of memristor-related parameters, and same results is obtained by varying stimuli-related parameters. In addition, the energy is proved to be another effective method to estimate stochastic resonance and inverse stochastic resonance. Furthermore, the analog implementation is achieved for the physical realization of the neuron. These results shed lights on the understanding of the firing mechanism for neurons detecting electromagnetic field.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39212726

RESUMO

Behaviors and auditory physiological responses of some species of echolocating bats remain unaffected after exposure to intense noise, but information on the underlying mechanisms remains limited. Here, we studied whether the vocalization-induced middle ear muscle (MEM) contractions (MEM reflex) and auditory fovea contributed to the unimpaired auditory sensitivity of constant frequency-frequency modulation (CF-FM) bats after exposure to broad-band intense noise. The vocalizations of the CF-FM bat, Hipposideros pratti, were inhibited through anesthesia to eliminate the vocalization-induced MEM reflex. First, the anesthetized bats were exposed to intense broad-band noise, and the findings showed that the bats could still maintain their auditory sensitivities. However, auditory sensitivities were seriously impaired in CBA/Ca mice exposed to intense noise under anesthesia. This indicated that the unimpaired auditory sensitivity in H. pratti after exposure to intense noise under anesthesia was not due to anesthetization. The bats were further exposed to low-frequency band-limited noise, whose passband did not overlap with echolocation call frequencies. The results showed that the auditory responses to sound frequencies within the noise spectrum and one-half octave higher than the spectrum were also unimpaired. Taken together, the results indicate that both vocalization-induced MEM reflex and auditory fovea do not contribute to the unimpaired auditory sensitivity in H. pratti after exposure to intense noise. The possible mechanisms underlying the unimpaired auditory sensitivity after echolocating bats were exposed to intense noise are discussed.

6.
Cell Death Dis ; 15(8): 630, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191749

RESUMO

Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Metástase Linfática , Camundongos Nus , MicroRNAs , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Exossomos/metabolismo , Camundongos , Linhagem Celular Tumoral , RNA Circular/genética , RNA Circular/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Masculino , Microambiente Tumoral , Transdução de Sinais , Proteínas de Grupo de Alta Mobilidade , Proteínas Repressoras
7.
Front Pharmacol ; 15: 1399829, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974033

RESUMO

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC). Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT. Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue. Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα. Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.

8.
Kaohsiung J Med Sci ; 40(8): 710-721, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837857

RESUMO

The proinflammatory properties of high-mobility group box protein 1 (HMGB1) in sepsis have been extensively studied. This study aimed to investigate the impact of HMGB1 on ferroptosis and its molecular mechanism in sepsis-induced acute lung injury (ALI). A septic mouse model was established using the cecal ligation and puncture method. Blocking HMGB1 resulted in improved survival rates, reduced lung injury, decreased levels of ferroptosis markers (reactive oxygen species, malondialdehyde, and Fe2+), and enhanced antioxidant enzyme activities (superoxide dismutase and catalase) in septic mice. In addition, knockdown of HMGB1 reduced cellular permeability, ferroptosis markers, and raised antioxidant enzyme levels in lipopolysaccharide (LPS)-stimulated MLE-12 cells. Silencing of HMGB1 led to elevations in the expressions of ferroptosis core-regulators in LPS-treated MLE-12 cells, such as solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member A2 (SLC3A2), and glutathione peroxidase 4. Furthermore, blocking HMGB1 did not alter ferroptosis, oxidative stress-related changes, and permeability in LPS-treated MLE-12 cells that were pretreated with ferrostatin-1 (a ferroptosis inhibitor). HMGB1 inhibition also led to elevated expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) in LPS-treated MLE-12 cells and lung tissues from septic mice. The Nrf2-specific inhibitor ML385 reversed the effects of HMGB1 silencing on ferroptosis and cell permeability in LPS-treated MLE-12 cells. Our findings indicated that the inhibition of HMGB1 restrains ferroptosis and oxidative stress, thereby alleviating sepsis-induced ALI through the activation of Nrf2 signaling.


Assuntos
Lesão Pulmonar Aguda , Ferroptose , Proteína HMGB1 , Lipopolissacarídeos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Sepse , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/genética , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Sepse/complicações , Sepse/metabolismo , Sepse/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Lipopolissacarídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Cicloexilaminas/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Fenilenodiaminas/farmacologia , Fenilenodiaminas/uso terapêutico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Sistema y+ de Transporte de Aminoácidos
9.
Phys Rev E ; 109(5-1): 054312, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38907474

RESUMO

The Brain Connectome Project has made significant strides in uncovering the structural connections within the brain on various levels. This has led to the question of how brain structure and function are related. Our research explores this relationship in an adaptive neural network in which synaptic conductance between neurons follows spike-time synaptic plasticity rules. By adjusting the plasticity boundary, the network exhibits diverse collective behaviors, including phase synchronization, phase locking, hierarchical synchronization (phase clusters), and coexisting states. Using graph theory, we found that hierarchical synchronization is related to the community structure, while coexisting states are related to the hierarchical self-organizing and core-periphery structure. The network evolves into several tightly connected modules, with sparsely intermodule connections resulting in the formation of phase clusters. In addition, the hierarchical self-organizing structure facilitates the emergence of coexisting states. The coexistence state promotes the evolution of the core-periphery structure. Our results point towards the equivalence between function and structure, with function emerging from structure, and structure being influenced by function in a complex dynamic process.

10.
Am J Transl Res ; 16(4): 1353-1365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715836

RESUMO

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

11.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1924-1931, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812205

RESUMO

The Chinese medical mechanism of Huanglian Jieduo Decoction on treating Alzheimer's disease(AD) characterized by "toxin damaging brain collateral" is still unclear. This study aims to explore the mechanism of Huanglian Jieduo Decoction on regulating triggering receptor expressed on myeloid cells 2(TREM2)/protein kinase B(Akt)/glycogen synthase kinase 3ß(GSK3ß) pathway to improve the cognitive deficit in APP/PS1 transgenic mice. APP/PS1 mice of approximately nine months old were randomly divided into the model group, the low, medium, and high(2.5, 5, and 10 g·kg~(-1)) groups of Huanglian Jiedu Decoction, and 0.75 mg·kg~(-1) donepezil hydrochloride group, and the C57BL/6J mice with the same age were taken as the normal group. After one month of continuous oral administration, a Morris water maze was performed to detect the learning and memory ability of mice. Hematoxylin-eosin(HE) staining was applied to observe the morphology of neuronal cells in the cortical area of mice. Immunofluorescence was used to detect the protein expressions of ß-amyloid(Aß_(1-42)), CD86, and arginase 1(Arg1). The mRNA levels of interleukin(IL)-1ß, IL-6, and IL-10 in the cortex of mice were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expressions of TREM2, phosphoinositide-3 kinase(PI3K), Akt, GSK3ß, and beta-catenin(ß-catenin) in mouse cortex were determined by Western blot. The results indicated that the escape latency of the model group was significantly prolonged, and the residence time in the target quadrant and the number of crossing the platform were significantly reduced compared with the normal group. Mice in the model group had a significantly lower number of neurons in the cortex and showed nuclear pyknosis and a significant increase in the expressions of Aß_(1-42) and CD86. The mRNA levels of IL-1ß and IL-6 in tissue were significantly increased, IL-10 were increased, while Arg1 were significantly decreased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin in the cortex were significantly down-regulated. Compared with the model group, the escape latency of the mice in the administration group was significantly shortened, and the number of crossing the platform and the residence time in the target quadrant were significantly increased. Furthermore, the number of neurons in the cortex of mice was increased, and nuclear pyknosis was improved. Aß_(1-42) deposition was decreased significantly. The mRNA levels of IL-1ß, IL-6 and CD86 were significantly decreased, while IL-10 and Arg1 levels were significantly increased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin protein in the cortex of each administration group was significantly up-regulated compared with the model group. In conclusion, Huanglian Jiedu Decoction reduced the expression of Aß_(1-42) and neuroinflammation to a neuro-protective effect, thereby improving the learning and memory ability in APP/PS1 mice, which may be related to the TREM2/Akt/GSK3ß signaling pathway.


Assuntos
Doença de Alzheimer , Córtex Cerebral , Medicamentos de Ervas Chinesas , Glicogênio Sintase Quinase 3 beta , Glicoproteínas de Membrana , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-akt , Receptores Imunológicos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Camundongos , Córtex Cerebral/metabolismo , Córtex Cerebral/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Masculino , Transdução de Sinais/efeitos dos fármacos , Humanos
12.
Huan Jing Ke Xue ; 45(5): 2840-2847, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629546

RESUMO

Investigating the relationship of soil aggregate stability with the organic carbon in the aggregate and its response to land use change is conducive to the estimation of soil carbon sink potential, improvement of rocky desertification, and rational land use in karst areas of Southwest China. In order to explore the effects of land use change on the composition and stability of soil aggregate stability as well as the content of aggregate organic carbon, the soil (0-30 cm) of five land use types (secondary forest, pomelo forest, paddy field, pepper forest, and dry land) was selected as the research object. The characteristics and correlation of soil aggregate components and organic carbon under different land use patterns were obtained, and the contribution of soil aggregates to the change in organic carbon after land use change was calculated. The results showed that the macroaggregates in the surface soil (0-15 cm) of the secondary forest, pomelo forest, and paddy field were 63.32%, 52.38%, and 47.77%, respectively, which were significantly higher than that of dry land (23.70%), as was also seen in the lower layer (15-30 cm). The geometric mean diameter (GMD) and mean weight diameter (MWD) of soil aggregates in the secondary forest, pomelo forest, and paddy field were significantly higher than those in dry land. In the surface soil, the organic carbon of the secondary forest and paddy field was significantly higher than that of other land use patterns. By contrast, in the lower soil layer, only the organic carbon of the paddy field was significantly higher than that of the others. Under different land use patterns, the organic carbon content of aggregates followed the same order of macroaggregates > microaggregates > silt and clay, indicating that macroaggregates allowed soil organic carbon to accumulate, whereas silt and clay did the opposite. According to correlation analysis, the content of soil macroaggregates was significantly positively correlated with GMD, MWD, and soil aggregate organic carbon, suggesting that the increase in soil macroaggregates could improve the stability of soil aggregates and store more soil organic carbon. Further, as land use change may have significantly affected the soil aggregate, moderate development of forestry and paddy cultivation is suggested to improve the soil carbon sequestration potential in the karst area of Southwest China.

13.
Pharmacol Biochem Behav ; 237: 173722, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38336220

RESUMO

The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.


Assuntos
Experiências Adversas da Infância , Fluoxetina , Humanos , Feminino , Camundongos , Masculino , Animais , Fluoxetina/farmacologia , Vortioxetina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico
14.
Adv Mater ; 36(15): e2310306, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38194699

RESUMO

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.


Assuntos
COVID-19 , Catepsina L , SARS-CoV-2 , Inibidores de Serina Proteinase , Animais , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Catepsina L/antagonistas & inibidores , Catepsina L/metabolismo , COVID-19/prevenção & controle , COVID-19/virologia , Eritrócitos , Pulmão/metabolismo , Peptídeo Hidrolases/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Inibidores de Serina Proteinase/uso terapêutico
15.
Huan Jing Ke Xue ; 45(1): 335-342, 2024 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-38216483

RESUMO

The composition of soil organic carbon and its stability mechanism are the key to understanding the terrestrial carbon sink capacity. The stability of soil organic carbon in a karst ecosystem greatly affects the soil carbon fixation capacity. In order to understand the impact of human activities on the stability of soil organic carbon in karst areas, the karst valley area of Zhongliang Mountain in Chongqing was selected as an example, and soil samples of four typical land use modes (mixed forest, bamboo forest, grassland, and cultivated land) were collected in layers to analyze the total organic carbon (TOC) and heavy fraction organic carbon (HFOC). The distribution characteristics of light fraction organic carbon (LFOC), labile organic carbon (LOC), and recalcitrant organic carbon (ROC) were analyzed quantitatively by using a structural equation model to provide basic data for soil carbon sink assessment and soil quality protection in karst areas. The results showed that the organic carbon components under different land use patterns in karst areas had obvious surface accumulation, and the content of organic carbon components in the surface layer was 1.2 times that in the bottom layer. Except for LFOC, the content of other organic carbon components was the highest in the mixed forest, followed by that in the bamboo forest and wasteland, with the lowest in cultivated land. Mixed forest ω(TOC) content was the highest, 42.5 g·kg-1, followed by that of bamboo forest (36.6 g·kg-1) and grassland (18.7 g·kg-1), and cultivated land content was the lowest, 13.4 g·kg-1. The soil organic carbon content of cultivated land was 68.5%, 63.5%, and 28.3% lower than that of mixed forest, bamboo forest, and grassland, respectively. Mixed forest had the highest content of ω(HFOC), 21 g·kg-1, followed by those of bamboo forest (20.9 g·kg-1), grassland (18.2 g·kg-1), and cultivated land (13.5 g·kg-1). The mixed forest ω(LOC) content was the highest, 16.3 g·kg-1, followed by those of bamboo forest (14.9 g·kg-1), grassland (11.5 g·kg-1), and cultivated land (5.3 g·kg-1). Mixed forest ω (ROC) content was the highest, 25.7 g·kg-1, followed by those of bamboo forest (21.6 g·kg-1), grassland (15.9 g·kg-1), and cultivated land (10.3 g·kg-1). The bamboo forest land ω(LFOC) content was 15.9 g·kg-1, followed by those of mixed forest (13.9 g·kg-1), grassland (7.3 g·kg-1), and cultivated land (4.9 g·kg-1). The recalcitrant organic carbon index (ROCI) was used to indicate the stability of soil organic carbon. The variation range of ROCI was 33.9%-64.5%, of which the highest was mixed forest (64.5%-66.3%), and the lowest was cultivated land (33.8%-39.6%). The ROCI of mixed forest, bamboo forest, and grassland were 1.8 times, 1.6 times, and 1.4 times that of cultivated land, respectively. Karst area ω (inert organic carbon) content and ROCI showed that human agricultural activities caused the reduction in soil organic carbon content and the destruction of soil physical structure, resulting in the accelerated decomposition and turnover rate of soil organic matter. The most important factor affecting soil stability in karst areas was soil pH. Tillage activities caused soil pH to rise, reduced soil microbial activity, and were not conducive to the accumulation of the inert organic carbon and soil organic carbon pool in the soil.

16.
Eur J Clin Nutr ; 78(2): 107-113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37935889

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Vírus da Hepatite B , Neoplasias Hepáticas/etiologia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Inibidores de Calcineurina , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatite B/complicações
17.
Int J Syst Evol Microbiol ; 73(11)2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37942742

RESUMO

Two novel rod-shaped, Gram-stain-negative, aerobic and non-motile bacterial strains, designated M39T and C2-7T, were isolated from the coastal sediment of Xiaoshi Island, Weihai, PR China. Growth of strain M39T occurred at 15-37 °C, at pH 6.0-9.0 and in the presence of 1.0-9.0 % (w/v) NaCl. Strain C2-7T grew at 15-40 °C, at pH 6.0-8.0 and in the presence of 0.5-8.0 % (w/v) NaCl. Phylogenetic analysis based 16S rRNA gene sequences revealed that strains M39T and C2-7T belong to the phylum Bacteroidota. Based on the results of 16S rRNA gene sequence analysis, the closest relative of strain M39T was Robiginitalea marina KCTC 92035T (95.4 %), and the closest relative of strain C2-7T was Algoriphagus namhaensis DPG-3T (97.0 %). The percentage of conserved protein and average nucleotide identity values between strain M39T and some species of the genus Robiginitalea were 66.9-77.6% and 69.3-71.0 %, respectively, while those between strain C2-7T and some species of the genus Algoriphagus were 68.0-70.1% and 56.1-72.6 %, respectively. The major cellular fatty acids (>10 %) of strain M39T consisted of iso-C15 : 1 F, iso-C15 : 0 and iso-C17 : 0 3-OH, while those of strain C2-7T were iso-C15 : 0 and C16 : 1 ω7c/C16 : 1 ω6c. MK-6 was the only respiratory quinone that was compatible with the genus of strain M39T. The predominant menaquinone of strain C2-7T was MK-7. The major polar lipids of strain M39T were phosphatidylethanolamine and glycolipids, and those of strain C2-7T were phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. The DNA G+C contents of strains M39T and C2-7T were 46.9 and 40.8 mol%, respectively. Based upon the results presented in this study, strains M39T and C2-7T represent novel species of the genera Robiginitalea and Algoriphagus, respectively, for which the names Robiginitalea aurantiaca sp. nov. and Algoriphagus sediminis sp. nov. are proposed with the type strains M39T (=MCCC 1H00498T=KCTC 92014T) and C2-7T (=MCCC 1H00414T=KCTC 92027T).


Assuntos
Flavobacteriaceae , Fosfatidiletanolaminas , Fosfatidiletanolaminas/química , Ácidos Graxos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Cloreto de Sódio , DNA Bacteriano/genética , Análise de Sequência de DNA , Composição de Bases , Técnicas de Tipagem Bacteriana , Flavobacteriaceae/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-37750765

RESUMO

Two novel Gram-stain-negative, facultative anaerobic, chemoheterotrophic, non-motile and rod-shaped strains were isolated from intertidal sediment sampled at Xiaoshi Island, Weihai, PR China. Full sequence analysis of the 16S rRNA genes showed that the two strains were closely related to members of the genus Winogradskyella and the phylogenetic similarities to their closest relative, Winogradskyella aquimaris, were 96.7 and 95.8 %, respectively. The DNA G+C contents of strains 2Y89T and D23T were 33.3 and 35.1 mol%, respectively. The respiratory quinone detected in both strains was MK-6. The major fatty acids detected in strain 2Y89T were iso-C15 : 0 and iso-C15 : 1G, and in strain D23T they were iso-C15 : 1G, iso-C15 : 0 and iso-C17 : 03-OH. The principal polar lipids of strain 2Y89T mainly included phosphatidylethanolamine, aminoglycolipids, unidentified aminolipids, unidentified glycolipids and unidentified lipids; strain D23T was the same as strain 2Y89T except that it did not contain aminoglycolipids. Based on the phenotypic, chemical taxonomic, genotypic and phylogenetic features established in this study, we suggest that the new strains represent two novel species of the genus Winogradskyella, for which the names Winogradskyella vincentii sp. nov. (type strain 2Y89T=MCCC 1H00477T=KCTC 92034T) and Winogradskyella alexanderae sp. nov. (type strain D23T=MCCC 1H00462T=KCTC 92023T) are proposed.


Assuntos
Bactérias , Ácidos Graxos , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , Ácidos Graxos/química , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
20.
Phys Rev E ; 108(1-1): 014205, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37583163

RESUMO

Over the past decade, dynamic schemes have been proposed for the use of bistable systems in the design of logic devices. A bistable system in a noisy background can operate as a reliable logic gate in a moderate noise level, which is called a logical stochastic resonance (LSR). In this paper, we theoretically explore the emergence of LSR in general bistable systems and identify the dynamical mechanisms of LSR. The timescale relationship between the measured time and the mean first-pass time of two-state transitions is a key condition in determining whether the system is reliable. Furthermore, we demonstrate that the stability of the logic operation can be significantly improved by choosing the appropriate filtering method. Low-pass filtered noise-driven systems are more stable than Gaussian white noise. However, band-pass and high-pass filtered noise are harmful to the stability of the system due to the filtering of low-frequency components. Our theoretical and numerical simulation results offer perspectives for the development of logic devices.

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