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1.
Front Pediatr ; 10: 963345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340725

RESUMO

Objective: To investigate the features and functions of the intestinal microbiota in neonates with necrotizing enterocolitis (NEC) in a single center in China. Methods: We collected clinical information and stool samples from 19 participants in our center, including 9 infants with necrotizing enterocolitis and 10 control infants. DNA was extracted from the samples, and 16S rRNA gene sequencing was used to analyse the participants' gut microbiota. Functional prediction was achieved using PICRUSt2. Results: Alpha diversity analysis found that similar levels of bacterial richness and diversity were found in the gut microbiota of infants with NEC and control infants (P = 0.1800), whereas beta diversity analysis suggested that the overall structures of the gut microbiota were significantly different (P = 0.0020). The Mann-Whitney U test of bacterial composition and abundance analysis revealed that the abundance levels of Proteobacteria (P = 0.03049) and Firmicutes (P = 0.01011) significantly differed between the two groups at the phylum level. Proteobacteria was the most abundant phylum in the NEC group. At the genus level, the abundance levels of Enterococcus (P = 0.0003), Streptococcaceae (P = 0.0109) and Lactobacillales (P = 0.0171) were significantly decreased in infants with NEC. Furthermore, the linear discriminant analysis effect size (LEfSe) method showed 12 bacterial taxa with significant differences in relative abundances in the two groups. Interestingly, members of Proteobacteria were enriched in NEC samples. In addition, functional prediction suggested that the microbial changes observed in infants with NEC resulted in a decline in galactose metabolism, the pentose phosphate pathway, fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and phosphotransferase system (PTS) pathways (P < 0.05). Conclusions: Our study shows the compositional and functional alterations of the intestinal microbiota in NEC, which will help demonstrate the relationship between the gut microbiota and NEC pathogenesis.

2.
Comput Math Methods Med ; 2022: 1643674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398072

RESUMO

Background: Transforming growth factor beta-induced protein (TGFBI, encoded by TGFBI gene), is an extracellular matrix protein, widely expressed in variety of tissues. It binds to collagens type I, II, and IV and plays important roles in the interactions of cell with cell, collagen, and matrix. It has been reported to be associated with myocardial fibrosis, and the latter is an important pathophysiologyical basis of atrial fibrillation (AF). However, the mechanism of TGFBI in AF remains unclear. We aimed to detect the potential mechanism of TGFBI in AF via bioinformatics analysis. Methods: The microarray dataset of GSE115574 was examined to detect the genes coexpressed with TGFBI from 14 left atrial tissue samples of AF patients. TGFBI coexpression genes were then screened using the R package. Using online analytical tools, we determined the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) annotation, and protein-protein interaction (PPI) network of TGFBI and its coexpression genes. The modules and hub genes of the PPI-network were then identified. Another dataset, GSE79768 was examined to verify the hub genes. DrugBank was used to detect the potential target drugs. Results: In GSE115574 dataset, a total of 1818 coexpression genes (769 positive and 1049 negative) were identified, enriched in 120 biological processes (BP), 38 cellular components (CC), 36 molecular functions (MF), and 39 KEGG pathways. A PPI-network with average 12.2-degree nodes was constructed. The genes clustered in the top module constructed from this network mainly play a role in PI3K-Akt signaling pathway, viral myocarditis, inflammatory bowel disease, and platelet activation. CXCL12, C3, FN1, COL1A2, ACTB, VCAM1, and MMP2 were identified and finally verified as the hub genes, mainly enriched in pathways like leukocyte transendothelial migration, PI3K-Akt signaling pathway, viral myocarditis, rheumatoid arthritis, and platelet activation. Pegcetacoplan, ocriplasmin, and carvedilol were the potential target drugs. Conclusions: We used microdataset to identify the potential functions and mechanisms of the TGFBI and its coexpression genes in AF patients. Our findings suggest that CXCL12, C3, FN1, COL1A2, ACTB, VCAM1, and MMP2 may be the hub genes.


Assuntos
Fibrilação Atrial , Miocardite , Humanos , Fibrilação Atrial/genética , Metaloproteinase 2 da Matriz , Perfilação da Expressão Gênica , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
3.
Mol Pharm ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368878

RESUMO

Regulating non-apoptotic cell death of cancer cells provides a promising strategy to overcome apoptosis resistance during cancer treatment. Lipids are essential components to exacerbate several non-apoptotic cell death pathways. In the present study, unsaturated fatty acid (UFA) liposomes prepared with linoleic acid, oleic acid, or α-linolenic acid have the potential to affect lipid metabolism. Notably, UFA liposomes markedly increased cellular reactive oxygen species (ROS) and down-regulated the expression of glutathione peroxidase 4 (GPX4) in tumor cells, resulting in lipid peroxidation, which in turn caused rapid membrane rupture and induced non-apoptotic cell death of tumor cells. Concomitantly, UFA liposomes induced ROS-mediated tumor-associated macrophages toward a tumoricidal phenotype to reverse the immunosuppressive tumor microenvironment. Consequently, UFA liposomes substantially inhibited tumor growth in a melanoma model by promoting lipid peroxidation, inducing non-apoptotic cell death of tumor cells, and increasing infiltration of anti-tumor immune cells at tumor sites. Therefore, UFA liposomes regulate GXP4 to exacerbate lipid peroxidation and provide a versatile liposome platform for enhancing anti-tumor therapy which could be readily extended to the delivery of anticancer agents.

4.
Future Oncol ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377828

RESUMO

Aim: To describe burden of chemotherapy-induced myelosuppression among chemotherapy-treated patients with extensive-stage small cell lung cancer (ES-SCLC). Materials & methods: Occurrence of grade ≥3 myelosuppressive hematological adverse events (HAEs), treatment patterns and healthcare resource utilization (HCRU) after chemotherapy initiation were evaluated using data from The US Oncology Network and Non-network clinics (1/1/2015-12/31/2020). Results: Among patients with laboratory values (Network: N = 1,374/1,574; Non-network: N = 661/959), over half-experienced grade ≥3 HAEs after chemotherapy initiation (Network = 56.6%; Non-network = 64.1%), and approximately one-third had grade ≥3 HAEs in at least two lineages (Network = 33.0%; Non-network = 31.3%). Patients with grade ≥3 HAEs had greater dose reductions, treatment delays and HCRU than those without. Conclusion: Myelosuppression is a burden to patients with ES-SCLC treated with chemotherapy and the healthcare system.


Our objective was to describe the burden of myelosuppression, a side effect of chemotherapy that results from damage to blood-forming cells in the bone marrow, among patients with extensive-stage small cell lung cancer (ES-SCLC). We evaluated the prevalence of myelosuppression, chemotherapy treatment patterns and outpatient healthcare use and costs after chemotherapy initiation using data from The US Oncology Network and Non-network clinics between 1 January 2015 and 31 December 2020. Among patients with laboratory values, which were required to identify myelosuppression events, over half of patients experienced severe myelosuppression-related adverse events in one or more lineages after chemotherapy initiation, and approximately one-third experienced severe myelosuppression-related adverse events in at least two blood cell lineages. Patients with severe myelosuppression-related adverse events had greater dose reductions, treatment delays, and healthcare use and costs than those without. Myelosuppression is a burden to patients with ES-SCLC treated with chemotherapy and the healthcare system. Reduction of chemotherapy-induced myelosuppression has the potential to reduce burden on patients and healthcare organizations.

5.
Elife ; 112022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399125

RESUMO

Cardiovascular disease is the leading cause of death worldwide due to the inability of adult heart to regenerate after injury. N6-methyladenosine (m6A) methylation catalyzed by the enzyme methyltransferase-like 3 (Mettl3) plays an important role in various physiological and pathological bioprocesses. However, the role of m6A in heart regeneration remains largely unclear. To study m6A function in heart regeneration, we modulated Mettl3 expression in vitro and in vivo. Knockdown of Mettl3 significantly increased the proliferation of cardiomyocytes and accelerated heart regeneration following heart injury in neonatal and adult mice. However, Mettl3 overexpression decreased cardiomyocyte proliferation and suppressed heart regeneration in postnatal mice. Conjoint analysis of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq identified Fgf16 as a downstream target of Mettl3-mediated m6A modification during postnatal heart regeneration. RIP-qPCR and luciferase reporter assays revealed that Mettl3 negatively regulates Fgf16 mRNA expression in an m6A-Ythdf2-dependent manner. The silencing of Fgf16 suppressed the proliferation of cardiomyocytes. However, the overexpression of ΔFgf16, in which the m6A consensus sequence was mutated, significantly increased cardiomyocyte proliferation and accelerated heart regeneration in postnatal mice compared with wild-type Fgf16. Our data demonstrate that Mettl3 post-transcriptionally reduces Fgf16 mRNA levels through an m6A-Ythdf2-dependen pathway, thereby controlling cardiomyocyte proliferation and heart regeneration.


Cardiovascular diseases are one of the world's biggest killers. Even for patients who survive a heart attack, recovery can be difficult. This is because ­ unlike some amphibians and fish ­ humans lack the ability to produce enough new heart muscle cells to replace damaged tissue after a heart injury. In other words, the human heart cannot repair itself. Molecules known as messenger RNA (mRNA) carry the 'instructions' from the DNA inside the cell nucleus to its protein-making machinery in the cytoplasm of the cell. These messenger molecules can also be altered by different enzymes that attach or remove chemical groups. These modifications can change the stability of the mRNA, or even 'silence' it altogether by stopping it from interacting with the protein-making machinery, thus halting production of the protein it encodes. For example, a protein called Mettl3 can attach a methyl group to a specific part of the mRNA, causing a reversible mRNA modification known as m6A. This type of alteration has been shown to play a role in many conditions, including heart disease, but it has been unclear whether m6A could also be important for the regeneration of heart tissue. To find out more, Jiang, Liu, Chen et al. studied heart injury in mice of various ages. Newborn mice can regenerate their heart muscle for a short time, but adult mice lack this ability, which makes them a useful model to study heart disease. Analyses of the proteins and mRNAs in mouse heart cells confirmed that both Mettl3 and m6A-modified mRNAs were present. The amount of each also increased with age. Next, experiments in genetically manipulated mice revealed that removing Mettl3 greatly improved tissue repair after heart injury in both newborn and adult mice. In contrast, mouse hearts that produced abnormally high quantities of Mettl3 were unable to regenerate ­ even if the mice were young. Moreover, a detailed analysis of gene activity revealed that Mettl3 was suppressing heart regeneration by decreasing the production of a growth-promoting protein called FGF16. These results reveal a key biological mechanism controlling the heart's ability to repair itself after injury. In the future, Jiang et al. hope that Mettl3 can be harnessed for new, effective therapies to promote heart regeneration in patients suffering from heart disease.


Assuntos
Metiltransferases , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Metilação , Fatores de Transcrição/metabolismo , Proliferação de Células
6.
Int J Mol Sci ; 23(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36430617

RESUMO

Transient receptor potential vanillic acid 1 (TRPV1) is an ion channel activated by heat and inflammatory factors involved in the development of various types of pain. The P2X7 receptor is in the P2X family and is associated with pain mediated by satellite glial cells. There might be some connection between the P2X7 receptor and TRPV1 in neuropathic pain in diabetic rats. A type 2 diabetic neuropathic pain rat model was induced using high glucose and high-fat diet for 4 weeks and low-dose streptozocin (35 mg/kg) intraperitoneal injection to destroy islet B cells. Male Sprague Dawley rats were administrated by intrathecal injection of P2X7 shRNA and p38 inhibitor, and we recorded abnormal mechanical and thermal pain and nociceptive hyperalgesia. One week later, the dorsal root ganglia from the L4-L6 segment of the spinal cord were harvested for subsequent experiments. We measured pro-inflammatory cytokines, examined the relationship between TRPV1 on neurons and P2X7 receptor on satellite glial cells by measuring protein and transcription levels of P2X7 receptor and TRPV1, and measured protein expression in the PKCε/P38 MAPK/NF-κB signaling pathway after intrathecal injection. P2X7 shRNA and p38 inhibitor relieved hyperalgesia in diabetic neuropathic pain rats and modulated inflammatory factors in vivo. P2X7 shRNA and P38 inhibitors significantly reduced TRPV1 expression by downregulating the PKCε/P38 MAPK/NF-κB signaling pathway and inflammatory factors in dorsal root ganglia. Intrathecal injection of P2X7 shRNA alleviates nociceptive reactions in rats with diabetic neuropathic pain involving TRPV1 via PKCε/P38 MAPK/NF-κB signaling pathway.

7.
Front Vet Sci ; 9: 1045152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425118

RESUMO

This study investigated the effect of Danggui Buxue decoction (DBD) on the immunity of an O-type foot-and-mouth disease (FMD) vaccine and intestinal mucosal immunity. SPF KM mice were continuously and orally administered DBD for 5 d and then inoculated with an O-type FMD vaccine. The contents of a specific IgG antibody and its isotypes IgG1, IgG2a, IgG2b, and IgG3 in serum and SIgA in duodenal mucosa were determined by ELISA at 1 and 3 W after the 2nd immunization. qRT-PCR was used to detect mRNA expression levels of IL-4, IL-10, IFN-γ, and IL-33 in the spleen, and mRNA expression levels of J-chain, pIgR, BAFF, APRIL, IL-10, IFN-γ and IL-33 in the duodenum. The results showed that compared with the control group, oral administration of DBD significantly increased levels of the anti-FMD virus (FMDV)-specific antibodies IgG, IgG1, and IgG2a in the serum of O-type FMD vaccine-immunized mice 1 W after the 2nd immunization (P < 0.05), upregulated mRNA expression levels of spleen lymphocyte cytokines IL-4 and IL-33 (P < 0.05), promoted the secretion of SIgA in duodenal mucosa (P < 0.05). The mRNA expression levels of J-chain, pIgR, BAFF, APRIL, IL-10, and IL-33 in duodenal tissues were upregulated (P < 0.05). This study indicates that DBD has a good promotion effect on the O-type FMD vaccine and the potential to be an oral immune booster.

8.
Heliyon ; 8(10): e10948, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36247122

RESUMO

Nowadays, the prognostic prediction of acute ischemic stroke (AIS) patients is still challenging because of the limited predictive properties of existing models. Blood-based biomarkers may provide additional information to the established prognostic factors. Markers of atherosclerosis have been identified as one of the most promising biomarkers for predicting prognosis, and inflammation, in turn, affects atherosclerosis. According to previous studies, the ratio of monocytes to lymphocytes (MLR) has been reported as a novel indicator of inflammation. Thus, our study was the first to conduct more in-depth research on the relationship between MLR and the prognosis of large artery atherosclerosis (LAA)-type AIS patients. A total of 296 patients with LAA-type stroke were recruited. Of these, 202 patients were assigned to the development cohort, and 94 patients were assigned to the validation cohort. In the development cohort, 202 patients were divided into groups A, B, C, and D according to the quartile method of MLR levels. The one-year prognosis of patients was tracked, and the modified Rankin scale (MRS, with a score ranging from 0 to 6) was mainly selected as the measurement result of the function. The relationship between MLR and prognosis was analyzed by building logistics regression models. The models showed that MLR made significant predictions in poor outcomes of LAA-type stroke patients (odds ratio: 4.037; p = 0.048). At the same time, receiver operating characteristics (ROC) curves were used to compare the predictive values between MLR and clinical prediction score (Barthel Index). This study demonstrated that patients with LAA-type stroke and high MLR had a poor prognosis. MLR might be a reliable, inexpensive, and novel predictor of LAA-type stroke prognosis.

9.
Front Microbiol ; 13: 996930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36274747

RESUMO

Coconut oil cake (COC), a byproduct of oil extraction, contains high levels of cellulose. The aim of this study was to isolate a cellulose-degrading yeast from rotten dahlia that can effectively use COC as the only carbon source for cellulase secretion. Based on screening, Meyerozyma guillermondii CBS 2030 (M. guillermondii) was identified as a potential candidate, with the highest cellulolytic activity among the yeast strains isolated, with the carboxymethyl cellulase (CMCase) activity reaching 102.96 U/mL on day 5. The cellulose in COC samples was evaluated before and after degradation by M. guillermondii. Analysis based on field emission scanning electron microscopy (FESEM) revealed that the COC structure was changed significantly during the treatment, indicating effective hydrolysis. Fourier transform infrared spectroscopy (FTIR) of the modified functional groups indicated successful depolymerization of coconut cake. X-ray diffraction (XRD) and analysis of color differences established effective degradation of COC by M. guillermondii. The results demonstrate that M. guillermondii effectively secretes CMCase and degrades cellulose, which has important practical significance in COC degradation.

10.
Sci Rep ; 12(1): 15976, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36156063

RESUMO

In this study, a novel approach for random vibration analysis of nonlinear frame structures under seismic random excitations is developed. The explicit time-domain method is improved in this approach by integrating the plastic hinge model, which can simulate the nonlinear behaviors caused by material property changes. Specifically, the hysteretic system's equation of motion is constructed using auxiliary differential equations that govern the plastic rotational displacements and their corresponding hysteretic displacements. Additionally, by introducing the concept of equivalent excitations, an explicit iteration scheme for solving the equation of the hysteretic system is developed, in which the auxiliary differential equations are solved under the assumption that the plastic rotational velocity changes linearly with time between two adjacent time instants. Finally, by combining the Monte Carlo simulation method and the proposed explicit time-domain method, the non-stationary random responses of nonlinear frame structures can be obtained. As illustrated by numerical examples, the proposed method achieves satisfactory solution accuracy and efficiency when applied to nonlinear frame structures with plastic hinges. Moreover, the proposed iterative method resolves equations involving displacements describing the frame's global state, plastic rotational displacements, and corresponding hysteretic parameters, introducing a novel concept for solving problems with nonlinear coupled variables of multiple types.

11.
J Neuroinflammation ; 19(1): 232, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131290

RESUMO

BACKGROUND: Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. METHODS: Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. RESULTS: Compared with controls, only MS animals in the adult stage (PND56-65) but not the adolescent stage (PND31-40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1ß, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35-65). CONCLUSIONS: MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.


Assuntos
Privação Materna , Sirtuína 3 , Animais , Bromodesoxiuridina/metabolismo , Cognição , Hipocampo/metabolismo , Interleucina-6/metabolismo , NAD/metabolismo , NAD/farmacologia , Neurônios/metabolismo , Niacinamida/metabolismo , Niacinamida/farmacologia , Ratos , Ratos Wistar , Maturidade Sexual , Fator de Necrose Tumoral alfa/metabolismo
12.
Microb Biotechnol ; 15(11): 2831-2844, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36069650

RESUMO

Expressing heterologous antigens by plasmids may cause antibiotic resistance. Additionally, antigen expression via plasmids is unstable due to the loss of the plasmid. Here, we developed a balanced-lethal system. The Listeria monocytogenes (LM) balanced-lethal system has been previously used as an antigen carrier to induce cellular immune response. However, thus far, there has been no reports on Listeria ivanovii (LI) balanced-lethal systems. The dal and dat genes from the LI-attenuated LIΔatcAplcB (LIΔ) were deleted consecutively, resulting in a nutrient-deficient LIΔdd strain. Subsequently, an antibiotic resistance-free plasmid carrying the LM dal gene was transformed into the nutrient-deficient strain to generate the LI balanced-lethal system LIΔdd:dal. The resultant bacterial strain retains the ability to proliferate in phagocytic cells, as well as the ability to adhere and invade hepatocytes. Its genetic composition was stable, and compared to the parent strain, the balanced-lethal system was substantially attenuated. In addition, LIΔdd:dal induced specific CD4+ /CD8+ T-cell responses and protected mice against LIΔ challenge. Similarly, we constructed an LM balanced-lethal system LMΔdd:dal. Sequential immunization with different recombinant Listeria strains will significantly enhance the immunotherapeutic effect. Thus, LIΔdd:dal combined with LMΔdd:dal, or with other balanced-lethal systems will be more promising alternative for vaccine development.


Assuntos
Listeria monocytogenes , Listeria , Vacinas contra a Tuberculose , Camundongos , Animais , Listeria/genética , Listeria/metabolismo , Vacinas contra a Tuberculose/genética , Listeria monocytogenes/genética , Vacinas Atenuadas/genética , Antibacterianos/metabolismo
13.
World J Clin Cases ; 10(18): 6277-6282, 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35949829

RESUMO

BACKGROUND: Brain arteriovenous malformation (AVM), an aberrant vascular development during the intrauterine period, is traditionally considered a congenital disease. Sporadic reports of cases of de novo AVM formation in children and adults have challenged the traditional view of its congenital origin. CASE SUMMARY: In this report, we have presented the case of a child with a de novo brain AVM. Magnetic resonance imaging and magnetic resonance angiography of the brain showed no AVM at the age of 5 years and 2 mo. Brain AVM was first detected in this child at the age of 7 years and 4 mo. The brain AVM was significantly advanced, and hemorrhage was seen for the first time at the age of 12 years and 8 mo. There was further progression in the AVM, and hemorrhage occurred again at the age of 13 years and 5 mo. Genetic analysis of this patient revealed a mutation in the NOTCH2 (p.Asp473Val) gene. CONCLUSION: In short, our case has once again confirmed the view that brain AVM is an acquired disease and is the result of the interaction of genes, environment, and molecules.

14.
Front Public Health ; 10: 920233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979472

RESUMO

The deterioration of the living environment caused by the earthquake is the main migration motivation of residents in the area of the secondary earthquake disaster, and their migration intention is one of the most important factors affecting residents' happiness. This paper uses 957 effective survey samples from 12 secondary geological disaster areas after the Wenchuan earthquake to research the migration intention of residents and its influencing factors. It can be found that 45.2% of residents are willing to migrate, which means they have an instinctive reaction to profit-seeking and harm-avoiding, but it has not become a realistic choice. Investigation facts and research results show that the instinctive response of profit-seeking and harm-avoiding drives residents to make different choices. The migration of residents in areas where secondary geological disasters occur is affected not only by disasters such as debris flow, landslides, and collapse, but also by many factors such as life convenience, family income, expectations for future life, gender, education level, psychological feeling. The improved life and the optimization of the economic conditions brought about by the success of post-disaster reconstruction have made the vast majority of people more confident in the future of the disaster-stricken areas, which made most people choose to stay in those areas. This paper will provide policy suggestions for residents' migration and the reconstruction of the local social governance system in secondary geological disaster areas, which is helpful to improve ecological livability and residents' happiness in the Wenchuan earthquake-stricken area.


Assuntos
Desastres , Terremotos , Humanos , Renda , Intenção , Inquéritos e Questionários
15.
Front Hum Neurosci ; 16: 928315, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959244

RESUMO

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity (FC). A longitudinal design was adopted to investigate the alteration in FC dynamics using a dynamic functional connectivity (dFC) approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation (rTMS) with the target at the left dorsolateral prefrontal cortex (DLPFC). Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs (TSZ, n = 27), while the other group only received antipsychotic drugs (DSZ, n = 26). Resting-state functional magnetic resonance imaging (fMRI) and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline (t1) and after 4-week treatment (t2). The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit (CTCC). For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression (SVR) results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS.

16.
Front Psychiatry ; 13: 956895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990049

RESUMO

Background: Inter-hemispheric disconnection is a primary pathological finding in schizophrenia. However, given the inherent complexity of this disease and its development, it remains unclear as to whether associated inter-hemispheric changes play an important role in auditory verbal hallucination (AVH) development. As such, this study was developed to explore inter-hemispheric connectivity in the context of schizophrenia with AVH while excluding positive symptoms and other factors with the potential to confound these results. Method: In total, resting-state functional magnetic resonance imaging (fMRI) was used to assess 42 patients with AVH (APG), 26 without AVH (NPG), and 82 normal control (NC) individuals. Inter-hemispheric connectivity in these subjects was then assessed through the use of voxel-mirrored homotopic connectivity (VMHC) and Pearson correlation analyses. Result: Relative to HC and NPG subjects, APG individuals exhibited a decrease in VMHC in the superior temporal gyrus (STG) extending into Heschl's gyrus, the insula, and the Rolandic operculum as well as in the fusiform gyrus extending into the para-hippocampus (Corrected p < 0.005, cluster size = 52). Among APG individuals, these observed impairments of inter-hemispheric connectivity were negatively correlated with Hoffman auditory hallucination scores. Conclusion: These results support the schizophrenia hemitropic disconnection hypothesis, and provide novel evidence suggesting that there may be a relationship between reductions in inter-hemispheric connectivity in auditory and memory-related networks and the pathogenesis of AVH in patients with schizophrenia following the exclusion of confounding factors from other positive symptoms.

17.
Ecotoxicol Environ Saf ; 243: 114015, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36030684

RESUMO

Cigarette smoke (CS) disrupts placental development, and impairs fetal health and maternal fertility, thus resulting in low birth weight, premature delivery, and spontaneous abortion; however, the underlying mechanisms remain unclear. This study investigated the mechanism through which CS impairs placental trophoblast cell viability and function. An in vivo study in pregnant rats exposed to CS indicated that CS- exposure decreased antioxidant factors expression and blocked NRF2 activation in the placenta. Anti-ferroptosis regulators expression was downregulated, and pro-ferroptosis regulators expression was upregulated in placentas from CS-exposed rats. Further analysis revealed that cigarette smoke extract (CSE) led to peroxins downregulation and decreased the number of peroxisomes. An in vitro study in HTR-8/SVneo(HTR-8) cells showed that CSE led to free iron and ROS accumulation, and subsequently induced lipid peroxidation and cell death. Ferroptosis inhibitors and the antioxidant L-arginine (ARG) partially inhibited CSE-induced cell death. ARG partially alleviated the toxic effects of CSE by promoting antioxidant factors expression in placenta and suppressing HTR-8 cell ferroptosis. Knockdown of PEX14, a peroxisome biogenesis marker, led to the downregulation of multiple PEXs, thus increasing intracellular H2O2 levels and inducing HTR-8 cell ferroptosis. These findings demonstrated that ferroptosis is responsible for CSE-induced trophoblast cell death and suggest that peroxisome dysfunction is involved in CSE-induced ferroptosis. Therefore, CSE-induced ferroptosis may serve as a potential therapeutic target for preventing adverse pregnancy outcomes.


Assuntos
Arginina , Fumar Cigarros , Ferroptose , Trofoblastos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Arginina/metabolismo , Arginina/farmacologia , Fumar Cigarros/efeitos adversos , Feminino , Peróxido de Hidrogênio/metabolismo , Proteínas de Membrana , Placenta/metabolismo , Gravidez , Ratos , Proteínas Repressoras/metabolismo , Fumaça/efeitos adversos , Tabaco
18.
Front Genet ; 13: 770569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836577

RESUMO

Background: Advanced and recurrent endometrial cancer EC remains controversial. Immunotherapy will play a landmark role in cancer treatment, and alternative splicing (AS) of messenger RNA (mRNA) may offer the potential of a broadened target space. Methods: We downloaded the clinical information and mRNA expression profiles from The Cancer Genome Atlas (TCGA) database. Hub genes were extracted from 11 AS-related genes to analyze the correlation between clinical parameters and the tumor-immune microenvironment. We also analyzed the correlations between the copy numbers, gene expressions of hub genes, and immune cells. The correlation between the risk score and the six most important checkpoint genes was also investigated. The ESTIMATE algorithm was finally performed on each EC sample based on the high- and low-risk groups. Results: The risk score was a reliable and stable independent risk predictor in the Uterine Corpus Endometrial Carcinoma (UCEC) cohort. CYB561|42921|AP and FOLH1|15817|ES were extracted. The expression of CYB561 and FOLH1 decreased gradually with the increased grade and International Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.05). Gene copy number changes in CYB561 and FOLH1 led to the deletion number of myeloid DC cells and T cell CD8+. Low expression of both CYB561 and FOLH1 was associated with poor prognosis (p < 0.001). The checkpoint genes, CTLA-4 and PDCD1, exhibited a negative correlation with the risk score of AS in UCEC. Conclusion: AS-related gene signatures were related to the immune-tumor microenvironment and prognosis. These outcomes were significant for studying EC's immune-related mechanisms and exploring novel prognostic predictors and precise therapy methods.

19.
ACS Appl Mater Interfaces ; 14(28): 32105-32111, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35791739

RESUMO

A nitro-decorated microporous covalent organic framework, TpPa-NO2, has been synthesized in a gram scale with a one-pot reaction. It can effectively selectively separate C2H4 from a C2H2/C2H4/CO2 mixture and capture CO2 from CO2/N2 based on ideal adsorption solution theory calculations and transient breakthrough experiments. Theoretical calculations illustrated that the hydrogen atoms of imine bonds, carbonyl oxygen, and nitro group show high affinity toward C2H2 and CO2, playing vital roles in efficient separation.

20.
Chem Sci ; 13(26): 7855-7862, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35865891

RESUMO

Ketyl-olefin coupling reactions stand as one of the fundamental chemical transformations in synthetic chemistry and have been widely employed in the generation of complex molecular architectures and natural product synthesis. However, catalytic ketyl-olefin coupling, until the recent development of photoredox chemistry and electrosynthesis through single-electron transfer mechanisms, has remained largely undeveloped. Herein, we describe a new approach to achieve catalytic ketyl-olefin coupling reactions by a halogen-atom transfer mechanism, which provides innovative and efficient access to various gem-difluorohomoallylic alcohols under mild conditions with broad substrate scope. Preliminary mechanistic experimental and computational studies demonstrate that this radical-to-polar crossover transformation could be achieved by sequentially orchestrated Lewis acid activation, halogen-atom transfer, radical addition, single-electron reduction and ß-fluoro elimination.

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