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1.
Huan Jing Ke Xue ; 44(1): 312-322, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635819

RESUMO

The net primary productivity (NPP) of vegetation, as an indispensable element in carbon cycle studies, characterizes plant growth status. This study applied MODIS NPP products from 2000 to 2020 and multi-source data on elevation, slope, precipitation, temperature, land use, and population density in Shanxi province. We used trend analysis, correlation analysis, and geographic probes to explore the spatial and temporal evolution characteristics and driving factors of NPP in Shanxi province and its national planned coal-mining areas. The results showed that: ① the overall NPP exhibited a fluctuating upward trend from 2000 to 2020, with an average rate of increase (in terms of C) of 6.7 g·(m2·a)-1. The total NPP varied significantly among different land types, with arable land>forest land>grassland>construction land>water area>unused land. ② The spatial heterogeneity of NPP changes was obvious, with lower NPP values in the western and northern regions and higher average NPP values in the eastern and southern regions; the NPP comparison of three major coal bases showed that Jindong coal base>Jinzhong coal base>Jinbei coal base. ③ The correlation between NPP and precipitation was high, with 62.2% of regions having a significant correlation (P<0.05), mainly in central and eastern Shanxi province. The relationship between NPP changes and temperature was weak, with only 1.10% of regions having a significant correlation (P<0.05). ④ The comparison of the q-means of each factor in different years based on geographic probes showed that precipitation (0.165)>land use (0.124)>population density (0.085)>slope (0.080)>elevation (0.064)>air temperature (0.024), further indicating that precipitation was the dominant driver of NPP changes over the years. 5 The influence of the two-factor interaction was significantly higher than that of the single factor, and the influence of anthropogenic factors was gradually increasing. From 2000 to 2020, the interaction factor precipitation∩population density (0.275) with the highest explanatory power replaced precipitation∩temperature (0.385) as the interaction factor precipitation with the highest explanatory power.


Assuntos
Ecossistema , Modelos Teóricos , Florestas , Temperatura , Carvão Mineral , China
2.
Neurotoxicol Teratol ; 94: 107133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36343875

RESUMO

In recent years, since the need for anesthetic interventions in pregnant women, newborns, and older patients has been increasing, the anesthesia-induced cognitive impairment has received widespread attention and highlighted the urgent requirement for preventive and therapeutic measures with low risk of side effects. Environmental enrichment (EE), a novel and easy-to-implement rehabilitation treatment strategy, exerts its protective potential on the cognitive abilities of developing and aging brains after anesthetic exposure. This review summarizes the improvement of cognition by EE described in recent studies and explores the molecular mechanisms by which EE exerts neuroprotective effects. The literature indicates that the intervention mode, timing, and duration of EE are vital to its effect.


Assuntos
Anestesia , Anestésicos , Transtornos Cognitivos , Disfunção Cognitiva , Gravidez , Humanos , Recém-Nascido , Feminino , Cognição , Transtornos Cognitivos/induzido quimicamente , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/terapia , Anestésicos/efeitos adversos
3.
Lipids Health Dis ; 21(1): 101, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229882

RESUMO

Many cardiovascular disorders, including atherosclerosis, hypertension, coronary heart disease, diabetes, etc., are characterized by endothelial cell dysfunction. Endothelial cell function is closely related to sphingolipid metabolism, and normal sphingolipid metabolism is critical for maintaining endothelial cell homeostasis. Sphingolipid metabolites or key enzymes in abnormal situation, including sphingosine, ceramide (Cer), sphingosine-1-phosphate (S1P), serine, sphingosine kinase (SPHK), ceramide kinase (Cerk), sphingosine-1-phosphate lyase (S1PL) etc., may have a protective or damaging effect on the function of endothelial cells. This review summarizes the effects of sphingolipid metabolites and key enzymes disordering in sphingolipid metabolism on endothelial cells, offering some insights into further research on the pathogenesis of cardiovascular diseases and corresponding therapeutic targets.


Assuntos
Esfingolipídeos , Esfingosina , Ceramidas/metabolismo , Células Endoteliais/metabolismo , Lisofosfolipídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Serina , Esfingolipídeos/metabolismo , Esfingosina/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-36199553

RESUMO

Objective: This study aims to explore the application effect of meditation relaxation training and the Rosenthal effect in patients with adenoidectomy. Methods: This study included 94 children who underwent adenoidectomy in our hospital from April 2020 to May 2022 and were divided into a study group and a control group. The control group was given routine care, and the study group was given meditation relaxation training and the Rosenthal effect on the basis of the control group. The negative emotions, treatment compliance, complication rates, and nursing satisfaction of children's family members before and after the intervention were compared between the two groups. Results: The results of this study showed that after the intervention, the CDI and SCARED scores of the children in the study group were significantly lower than those in the control group. The treatment compliance in the study group was significantly higher than that in the control group, and the incidence of complications was significantly lower than that in the control group. Conclusion: The intervention of meditation relaxation training and the Rosenthal effect on children with adenoidectomy can relieve their negative emotions, improve treatment compliance, reduce the incidence of complications, and the children's family members are more satisfied.

5.
Zhen Ci Yan Jiu ; 47(10): 878-84, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36301164

RESUMO

OBJECTIVE: To observe the effect of herbal cake-separated moxibustion (HCSM) on serum lactic acid (BLA) level and AMPK/PGC-1α signaling pathway in the quadriceps femoris in chronic fatigue syndrome (CFS) rats, so as to explore its mechanisms underlying improvement of CFS. METHODS: According to the random number table, 50 SD rats were divided into blank control, model, HCSM, sham HCSM and medication (herbal medicine gavage) groups, with 10 rats in each group. The CFS model was established by using chronic restraint and exhaustive swimming, alternately, once daily for 21 days. The herbal cake was made of Xiaoyao Powder (Mental Ease Powder, composed of [Danggui (Radix Angelicae Sinensis), Baishao (Radix Paeoniae Alba), Chaihu (Radix Bupleuri), Fuling (Poria), Baizhu (Rhizoma Atractylodis, Macrocephalae), etc.]. The HCSM was applied to "Shenque" (CV8), "Guanyuan "(CV4), bilateral "Zusanli" (ST36) and "Qimen" (LR14), 5 moxa-cones for each acupoint, once daily for 10 days. For sham HCSM, the excipient was instead of herbal cake, and the same 5 moxa-cones was given as the HCSM group. Rats of the medication group received gavage of Xiaoyao Powder suspension (60 mg·kg-1), once daily for 10 days. The open field test and tail suspension test were conducted for determining the animals' locomotor activity. The blood sample was taken from the abdominal aorta under anesthesia for assaying the levels of serum BLA, chemokine ligand CXCL9 and ß-endorphin (EP) by ELISA. Bilateral quadriceps femoris were sampled for observing histopathological changes after staining with conventional H.E. technique, and for detecting the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by using immunohistochemistry. RESULTS: Compared with the blank control group, the number of rearing and horizontal grid-crossing times, struggling times of tail suspension test were significantly decreased (P<0.05), and the immobility time was obviously prolonged (P<0.05) in the model group. Compared with the model group, both HCSM and medication groups had a significant increase of rearing, horizontal grid-crossing times and struggling times (P<0.05), and the immobility time had a significant decrease (P<0.05). But there were no significant differences in the total movement distance among the 5 groups (P>0.05), and in the 5 indexes of behavioral measurements between the HCSM and medication groups (P>0.05). The sham HCSM could also evidently increase the struggling times and reduce the immobility time (P<0.05). The contents of serum BLA, CXCL9 and ß-EP were obviously higher in the model group than in the blank control group (P<0.05), as well as remarkably lower in the HCSM and medication groups than in the model group (P<0.05). Whereas the expression levels of muscular p-AMPK and PGC-1α were considerably lower in the model group than in the blank control group (P<0.05), and significantly increased in both HCSM and medication groups relevant to the model group (P<0.05). Compared with the sham HCSM group, the contents of BLA, CXCL9 and ß-EP in serum of the HCSM group and contents of CXCL9, ß-EP in medication group were significantly decreased (P<0.05), and the protein expressions of p-AMPK and PGC-1α in quadriceps femoris in both HCSM and medication groups were significantly increased (P<0.05). H.E. staining showed smaller intercellular space, uneven cytoplasmic staining in some muscle fibers, nucleus pyknosis and condensation, and inflammatory cell infiltration in the model group, which was milder in both HCSM and medication groups. CONCLUSION: HCSM can mitigate the stress behavioral state in CFS rats, which may be related with its functions in lowering the levels of serum BLA, CXCL9 and ß-EP, and activating AMPK/PGC-1α signaling pathway (balancing energy metabolism) in the quadriceps femoris.


Assuntos
Síndrome de Fadiga Crônica , Moxibustão , Animais , Ratos , Proteínas Quinases Ativadas por AMP , beta-Endorfina , Síndrome de Fadiga Crônica/tratamento farmacológico , Ácido Láctico , Pós , Ratos Sprague-Dawley , Transdução de Sinais
6.
Front Plant Sci ; 13: 1020841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186026

RESUMO

A virus-induced gene silencing (VIGS) system was established to induce endogenous target gene silencing by post-transcriptional gene silencing (PTGS), which is a powerful tool for gene function analysis in plants. Compared with stable transgenic plant via Agrobacterium-mediated gene transformation, phenotypes after gene knockdown can be obtained rapidly, effectively, and high-throughput through VIGS system. This approach has been successfully applied to explore unknown gene functions involved in plant growth and development, physiological metabolism, and biotic and abiotic stresses in various plants. In this system, GhCLA1 was used as a general control, however, silencing of this gene leads to leaf albino, wilting, and plant death ultimately. As such, it cannot indicate the efficiency of target gene silencing throughout the whole plant growth period. To address this question, in this study, we developed a novel marker gene, Gossypium PIGMENT GLAND FORMATION GENE (GoPGF), as the control to trace the efficiency of gene silencing in the infected tissues. GoPGF has been proved a key gene in gland forming. Suppression of GoPGF does not affect the normal growth and development of cotton. The number of gland altered related to the expression level of GoPGF gene. So it is a good marker that be used to trace the whole growth stages of plant. Moreover, we further developed a method of friction inoculation to enhance and extend the efficiency of VIGS, which facilitates the analysis of gene function in both the vegetative stage and reproductive stage. This improved VIGS technology will be a powerful tool for the rapid functional identification of unknown genes in genomes.

7.
J Psychopharmacol ; 36(10): 1176-1187, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36069168

RESUMO

BACKGROUND: Intracerebral translocator protein 18 kDa (TSPO) mediates the transport of cholesterol from cytoplasm to mitochondria and activation of microglia. The change of TSPO and the dysfunction of microglia are closely related to the pathogenesis of Alzheimer's disease (AD). AIMS: This study aimed to investigate the effects of microglial TSPO and its selective ligand YL-IPA08 on the cognitive function of transgenic mice in 5 × familial Alzheimer's disease (FAD) mouse model of AD. METHODS: The TSPO knockout 5 × FAD transgenic mice were bred, and tested by Morris water maze. The effects of YL-IPA08 on cognitive abilities and expression of Aß in 5 × FAD mice were also explored into. RESULTS: The latency of escape by TSPO knockout 5 × FAD mice was significantly prolonged compared with the 5 × FAD group, indicating that the cognitive impairment of mice aggravated. With the attenuated phagocytic ability of microglia, the deposition of Aß in prefrontal cortex of TSPO knockout 5 × FAD mice increased, and the expression of proinflammatory factors (IL-1ß, TNF-α, IL-6) were upregulated. In addition, YL-IPA08 significantly reduced the latency of escape by 5 × FAD mice, increased the number of times of crossing over the platform by mice, and inhibited the deposition of Aß in the prefrontal cortex of 5 × FAD mice without affecting the cleavage of APP. CONCLUSION: Our findings suggested that TSPO knockout in 5 × FAD mice inhibited microglial phagocytosis, promoted Aß deposition and neuroinflammation, and aggravated cognitive dysfunction in AD mice. YL-IPA08 had a significant cognition-enhancing effect in 5 × FAD transgenic mice, which might provide a new basis for potential drug candidates in AD treatment.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Cognição , Modelos Animais de Doenças , Flavina-Adenina Dinucleotídeo/metabolismo , Flavina-Adenina Dinucleotídeo/farmacologia , Imidazóis , Interleucina-6/metabolismo , Ligantes , Camundongos , Camundongos Transgênicos , Microglia , Piridinas , Fator de Necrose Tumoral alfa/metabolismo
8.
Stem Cells Dev ; 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36114617

RESUMO

Reserve mesenchyme cells (RMCs) are a type of antler stem cells (ASCs) that contribute to the rapid growth of deer antlers, the only known mammalian organ that can fully regenerate annually. Based on the prior evidence, ASC-conditioned medium could improve regenerative cutaneous healing in rats. The purpose of the study was to evaluate the therapeutic effects of RMC-conditioned medium (RMC-CM) on reducing the destruction in the mice periodontitis (PD) model and the underlying mechanisms. The lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used in vitro to verify the effects of RMC-CM. The results revealed that RMC-CM could significantly reduce bone resorption and osteoclast activation, upregulate anti-inflammatory macrophages (M2) related interleukin (IL)-10 and CD206, and downregulate pro-inflammatory macrophages (M1) related tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase in vivo. In vitro, RMC-CM could significantly promote LPS-stimulated RAW264.7 cells migration, reduce osteoclast differentiation, downregulate the expression of TNF-α, IL-6, and IL-1ß, and upregulate the expression of IL-10 and arginase 1. According to the results, we concluded that RMC-CM could significantly reduce alveolar bone resorption and inhibit inflammation in gingival tissue by decreasing the activation of osteoclasts and inducing macrophage polarization toward the M2 phenotype. This study may serve as the experimental foundation for RMC-CM in the treatment of PD.

9.
Int J Mol Sci ; 23(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36142835

RESUMO

Both zearalenone (ZEA) and lipopolysaccharide (LPS) can induce oxidative stress, and even apoptosis in bovine mammary epithelial cells (MAC-T), but not much attention has been given to the synergistic effect of ZEA and LPS. In this study, we treated MAC-T cells with different concentrations of LPS (1, 10, 50, and 100 µg/mL) and ZEA (5, 15, and 30 µM) to induce cell damage. Previous results show that MAC-T cell viability decreases with increasing LPS concentration. Meanwhile, 1 µg/mL LPS and ZEA were selected for combined treatment in subsequent studies. It was found that co-treatment with ZEA and LPS increases the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreases mitochondrial membrane potential (MMP), and superoxide dismutase (SOD), and reduces glutathione (GSH). ZEA and LPS are found to activate endoplasmic reticulum (ER) stress by increasing the expression of glucose-regulated protein 78 kDa (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP). It increases cell apoptosis by suppressing the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), indicated by up-regulation of Bcl2-associated X protein (Bax) and Cysteinyl aspartate-specific proteinases 3 (caspase-3) expression. The above results suggest that the synergistic effect of ZEA and LPS aggravate cytotoxicity.


Assuntos
Estresse do Retículo Endoplasmático , Zearalenona , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose , Ácido Aspártico/metabolismo , Caspase 3/metabolismo , Bovinos , Células Epiteliais/metabolismo , Glucose/metabolismo , Glutationa/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/toxicidade , Malondialdeído/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Zearalenona/metabolismo , Zearalenona/toxicidade , Proteína X Associada a bcl-2/metabolismo
10.
iScience ; 25(9): 104936, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36072549

RESUMO

Bone cancer pain is a common symptom in cancer patients with bone metastases and its underlying mechanisms remain unknown. Here, we report that Runx1 directly upregulates the transcriptional activity of P2X3 receptor (P2X3R) gene promoter in PC12 cells. Knocking down Runx1 in dorsal root ganglion (DRG) neurons suppresses the functional upregulation of P2X3R, attenuates neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats, whereas overexpressing Runx1 promotes P2X3R gene transcription in DRG neurons, induces neuronal hyperexcitability and pain hypersensitivity in naïve rats. Activation of GDNF-GFRα1-Ret-ERK signaling is required for Runx1-mediated P2X3R gene transcription in DRG neurons, and contributes to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. These findings indicate that the Runx1-mediated P2X3R gene transcription resulted from activation of GDNF-GFRα1-Ret-ERK signaling contributes to the sensitization of DRG neurons and pathogenesis of bone cancer pain. Our findings identify a potentially targetable mechanism that may cause bone metastasis-associated pain in cancer patients.

11.
Nature ; 609(7926): 369-374, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36045296

RESUMO

Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1-7. However, CAR-T cell therapy currently has several limitations8-12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR-Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469 ), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.


Assuntos
Imunoterapia Adotiva , Linfoma de Células B , Receptores de Antígenos Quiméricos , Animais , Antígenos CD19/imunologia , Eletroporação , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Células T de Memória/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico , Recidiva , Análise de Célula Única , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Front Endocrinol (Lausanne) ; 13: 905703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034435

RESUMO

Objectives: The progressive impairment of ß-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet ß-cells. Methods: Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and ß-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in ß-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells. Results: Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of ß-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of ß-TC6 cells. The expression of Cdc42 and p-p38 in ß-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells. Conclusions: Cdc42 in podocytes plays a crucial role in insulin secretion by ß-cells, which may provide a new therapeutic target to prevent the vicious cycle of ß-cell dysfunction in T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insulinas , Podócitos , Proteína cdc42 de Ligação ao GTP/metabolismo , Animais , Apoptose , Glucose , Secreção de Insulina , Camundongos , Superóxido Dismutase , Regulação para Cima
13.
Front Genet ; 13: 949989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938033

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen "albumin paclitaxel + cisplatin," but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 105 IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

14.
Nano Lett ; 22(16): 6664-6670, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35920806

RESUMO

Photogeneration of charge carriers in semiconductors provides the scientific fundamental for photocatalytic water splitting. However, an ongoing challenge is the development of a new mechanism promoting charge carrier separation. Here we propose a trap-state-induced interfacial charge-transfer transition mechanism (TSICTT), in which electrons in long-lived trap states recombine with holes on the valence band (VB) of the semiconductor, thus prolonging the electron lifetime. We demonstrate this concept in the Sr4Al14O25:Eu2+, Dy3+/CdS (SAO/CdS) heterostructure, where trapped electrons with a lifetime of up to several hours in the SAO persistent luminescence phosphor (PLP) can continuously consume holes on the VB of CdS nanoparticles (NPs). We discover that the interfacial interaction and the work function difference between SAO and CdS are crucial for the TSICTT, which finally contributes to the improved H2 production from 34.4 to 1212.9 µmol gCdS-1 h-1 under visible-light irradiation. This model introduces a new strategy to manipulate charge carrier transport for the effective utilization of solar energy.

15.
Clin Chim Acta ; 533: 131-143, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35779624

RESUMO

BACKGROUND: In the current environment of increasing social pressure, anxiety disorder has become a kind of health problem that needs to be solved urgently. However, the pathological mechanism of anxiety is still unclear, the classification of clinical diagnosis and symptoms is complex, and there is still a lack of biomarkers that can be identified and judged. METHODS: This study used LC-MS and non-targeted metabolomics to analyze the clinically collected plasma of 18 samples from anxiety disorder patients and 31 samples from healthy people to screen differential metabolites and perform subsequent metabolic pathway analysis. Binary Logistic regression was used to construct the anxiety disorder diagnosis prediction model and evaluate the prediction efficacy. RESULTS: The results showed that 22 metabolites were disturbed in the plasma of anxiety patients compared with healthy people. These metabolites mainly participate in 6 metabolic pathways. The combined diagnostic factors 4-Acetamidobutanoate, 3-Hydroxysebacic acid, and Cytosine were used to construct the diagnosis prediction model. The prediction probability of the model is 91.8%, the Youden index is 0.889, the sensitivity is 0.889, and the specificity is 1.000, so the prediction effect is good. CONCLUSIONS: This study preliminarily analyzed and explored the differences between plasma samples from patients with anxiety disorder and healthy individuals, increased the types of potential biomarkers for anxiety disorder, and provided a valuable reference for subsequent research related to anxiety disorder.


Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Transtornos de Ansiedade/diagnóstico , Biomarcadores , Estudos de Casos e Controles , Cromatografia Líquida , Humanos , Metabolômica/métodos
16.
Entropy (Basel) ; 24(7)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35885079

RESUMO

This paper studies the agent identity privacy problem in the scalar linear quadratic Gaussian (LQG) control system. The agent identity is a binary hypothesis: Agent A or Agent B. An eavesdropper is assumed to make a hypothesis testing the agent identity based on the intercepted environment state sequence. The privacy risk is measured by the Kullback-Leibler divergence between the probability distributions of state sequences under two hypotheses. By taking into account both the accumulative control reward and privacy risk, an optimization problem of the policy of Agent B is formulated. This paper shows that the optimal deterministic privacy-preserving LQG policy of Agent B is a linear mapping. A sufficient condition is given to guarantee that the optimal deterministic privacy-preserving policy is time-invariant in the asymptotic regime. It is also shown that adding an independent Gaussian random process noise to the linear mapping of the optimal deterministic privacy-preserving policy cannot improve the performance of Agent B. The numerical experiments justify the theoretic results and illustrate the reward-privacy trade-off.

17.
Front Surg ; 9: 855600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784935

RESUMO

Purpose: We designed a J-shaped external fixator (J-EF) to provide a minimally invasive, one-step surgical method for olecranon fractures. The aim of this study is to retrospectively review the method and the outcomes in 14 patients treated with J-EF fixation. Methods: Biomechanical comparative study was performed to test the tensile properties of the J-EF using a universal testing machine. Between January 2002 and December 2005, 14 patients (age range: 25-67 years) with Mayo type II olecranon fractures were treated using the external fixation technique. Follow-up was done by standard measures (radiography, range of motion, and complications monitoring) and patient-reported outcomes (Mayo Elbow Performance Score [MEPS] and Disabilities of the Arm, Shoulder, and Hand [DASH] scores) 6 months after surgery. Eight of the patients were reviewed 15 years after the surgery. Results: Results from biomechanical studies indicate the non-inferiority of J-EF to tension-band wiring (TBW) in tensile properties. At the time of release, the mean elbow flexion arc was 132.5° and the mean forearm rotation arc was 173.6°. The mean DASH score was 14.1 points, and the mean MEPS was 93.9 points. Operative time and intraoperative blood loss were decreased by 41.3% and 64.6%, respectively, in J-EF patients than those in a comparable group treated by TBW. All eight patients are still alive after the surgery and maintaining the original outcome. Conclusions: External fixation using the J-EF could be considered as an alternative treatment for Mayo type II olecranon fractures as it appears to be a reliable, minimally invasive, and time-saving. Level of Evidence: Therapeutic Level IV.

18.
Transl Stroke Res ; 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906328

RESUMO

Circulating neutrophils are activated shortly after stroke and in turn affect the fate of ischemic brain tissue, and microRNAs (miRNA) participate in regulating neuroinflammation. We probed the role of neutrophilic miRNA in ischemic stroke. miR-193a-5p was decreased in circulating neutrophils of acute ischemic stroke (AIS) patients and healthy controls. In another set of AIS patients treated with recombinant tissue plasminogen activator, higher neutrophilic miR-193a-5p levels were associated with favorable outcomes at 3 months and non-symptomatic intracerebral hemorrhage. An experimental stroke model and human neutrophil-like HL-60 cells were further transfected with agomiR-193a-5p/antagomiR-193a-5p or ubiquitin-conjugating enzyme V2 (UBE2V2)-siRNA prior to model induction for in vivo and in vitro studies. Results of 2,3,5-triphenyl tetrazolium chloride staining and neurological function evaluations at post-experimental stroke showed that intravenous agomiR-193a-5p transfusion protected against ischemic cerebral injury in the acute stage and promoted neurological recovery in the subacute stage. This protective role was suggested to correlate with neutrophil N2 transformation based on the N2-like neutrophil proportions in the bone marrow, peripheral blood, and spleen of the experimental stroke model and the measurement of neutrophil phenotype-associated molecule levels. Mechanistically, analyses indicated that UBE2V2 might be a target of miR-193a-5p. Cerebral injury and neuroinflammation aggravated by miR-193a-5p inhibition were reversed by UBE2V2 silencing. In conclusion, miR-193a-5p protects against cerebral ischemic injury by restoring neutrophil N2 phenotype-associated neuroinflammation suppression, likely, in part, via UBE2V2 induction.

19.
Plant Physiol Biochem ; 186: 76-87, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35820349

RESUMO

Drought stress commonly happens more than once during the life cycle of perennial trees. Stress memory endows better capacity to cope with repeated stresses for plants, while the underlying mechanisms are not fully elucidated. In this study, 2-month-old saplings of two mulberry cultivars (Husang32 and 7307 of Morus multicaulis) with or without an early soil water deficit were subjected to subsequent drought for 9 days. The shoot height growth, biomass production, stable carbon isotope discrimination, phytohormones, reactive oxygen species (ROS), osmotic substances and antioxidant enzymes were analyzed after the first and the second drought, respectively. Drought priming saplings sustained comparable or slightly higher biomass accumulation under the second drought than those non-priming. They also exhibited decreased levels of soluble sugars, free proline and soluble proteins, lower accumulation of malonaldehyde (MDA) and superoxide anion (O2•-), reduced activities of superoxide dismutase (SOD) and peroxidase (POD) compared to non-priming plants. Moreover, cultivar Husang32 exhibited elevated abscisic acid (ABA) and jasmonic acid (JA) where 7307 displayed opposite changes. PCA suggests that MDA, H2O2, free proline, SOD and POD in roots, and ROS, soluble sugars and glutamate reductase in leaves are dominant factors influenced by stress memory. ABA and JA in leaves also play important roles in exerting drought imprints. Collectively, stress memory can confer mulberry resistance to recurrent drought via combined regulations of antioxidative protection, osmotic adjustment and phytohormonal responses.


Assuntos
Secas , Morus , Ácido Abscísico/metabolismo , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Morus/fisiologia , Reguladores de Crescimento de Plantas , Prolina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Açúcares , Superóxido Dismutase/metabolismo
20.
J Transl Med ; 20(1): 279, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729576

RESUMO

Periodontitis is an inflammatory disease initiated by dysbiosis of the local microbial community. Periodontitis can result in destruction of tooth-supporting tissue; however, overactivation of the host immune response is the main reason for alveolar bone loss. Periodontal tissue cells, immune cells, and even further activated osteoclasts and neutrophils play pro-inflammatory or anti-inflammatory roles. Traditional therapies for periodontitis are effective in reducing the microbial quantities and improving the clinical symptoms of periodontitis. However, these methods are non-selective, and it is still challenging to achieve an ideal treatment effect in clinics using the currently available treatments and approaches. Exosomes have shown promising potential in various preclinical and clinical studies, including in the diagnosis and treatment of periodontitis. Exos can be secreted by almost all types of cells, containing specific substances of cells: RNA, free fatty acids, proteins, surface receptors and cytokines. Exos act as local and systemic intercellular communication medium, play significant roles in various biological functions, and regulate physiological and pathological processes in numerous diseases. Exos-based periodontitis diagnosis and treatment strategies have been reported to obtain the potential to overcome the drawbacks of traditional therapies. This review focuses on the accumulating evidence from the last 5 years, indicating the therapeutic potential of the Exos in preclinical and clinical studies of periodontitis. Recent advances on Exos-based periodontitis diagnosis and treatment strategies, existing challenges, and prospect are summarized as guidance to improve the effectiveness of Exos on periodontitis in clinics.


Assuntos
Perda do Osso Alveolar , Exossomos , Periodontite , Perda do Osso Alveolar/patologia , Citocinas/metabolismo , Exossomos/metabolismo , Humanos , Osteoclastos/patologia , Periodontite/diagnóstico , Periodontite/terapia
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