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1.
Environ Sci Technol ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978795

RESUMO

Electron transfer mediated by iron minerals is considered as a critical redox step for the dynamics of pollutants in soil. Herein, we explored the reduction process of Cr(VI) with different crystalline ferric oxyhydroxides in the presence of pyrogenic carbon (biochar). Both low- and high-crystallinity ferric oxyhydroxides induced Cr(VI) immobilization mainly via the sorption process, with a limited reduction process. However, the Cr(VI) reduction immobilization was inspired by the copresence of biochar. Low-crystallinity ferric oxyhydroxide had an intense chemical combination with biochar and strong sorption for Cr(VI) via inner-sphere complexation, leading to the indirect electron transfer route for Cr(VI) reduction, that is, the electron first transferred from biochar to iron mineral through C-O-Fe binding and then to Cr(VI) with Fe(III)/Fe(II) transformation on ferric oxyhydroxides. With increasing crystallinity of ferric oxyhydroxides, the direct electron transfer between biochar and Cr(VI) became the main electron transfer avenue for Cr(VI) reduction. The indirect electron transfer was suppressed in the high-crystallinity ferric oxyhydroxides due to less sorption of Cr(VI), limited combination with biochar, and higher iron stability. This study demonstrates that electron transfer mechanisms involving iron minerals change with the mineral crystallization process, which would affect the geochemical process of contaminants with pyrogenic carbon.

2.
Redox Biol ; 49: 102227, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34979450

RESUMO

Copper (Cu) is a necessary micronutrient at lower concentration, while excessive Cu exposure or Cu homeostasis disorders can lead to toxicity. The mechanism of male reproductive toxicity induced by Cu is still unknown. This study aims to investigate whether autophagy plays an important role in copper-induced spermatogenesis disorder in vivo and vitro. The present study showed that copper sulfate (CuSO4) might significantly promote autophagy level in the testis and mouse-derived spermatogonia cell line GC-1 spg cells. Concurrently, CuSO4 could induce autophagy via AMPK-mTOR pathway that downregulated p-mTOR/mTOR and subsequently upregulated p-AMPKα/AMPKα as well as p-ULK1/ULK1. In the meanwhile, CuSO4 treatment could also increase expression levels of the autophagy-related proteins. Then, the role of oxidative stress in CuSO4-induced autophagy was investigated. The findings demonstrated that oxidative stress inhibitor (NAC) attenuated CuSO4-induced autophagy in vivo and vitro, reversing the activation for AMPK-mTOR pathway. Additionally, the study also investigated how autophagy worked under the spermatogenesis disorder induced by CuSO4. Inhibition of autophagy could decrease cell viability, and enhance the ROS accumulation and apoptosis in the GC-1 cells, meanwhile, the spermatogenesis disorder, oxidative stress and histopathological changes were increased in the testis. Furthermore, co-treatment with the apoptosis inhibitor (Z-VAD-FMK) could decrease the spermatogenesis disorder but not influence autophagy. Besides, the crosslink between autophagy and ferroptosis were also measured, the data showed that inhibition of autophagy could suppress CuSO4-induced ferroptosis in in vivo and vitro. Altogether, abovementioned results indicated that CuSO4 induced autophagy via oxidative stress-dependent AMPK-mTOR pathway in the GC-1 cells and testis, and autophagy activation possibly led to the generation of protection mechanism through oxidative damage and apoptosis inhibition, however, autophagy also aggravate CuSO4 toxicology through promoting ferroptosis. Overall, autophagy plays a positive role for attenuating CuSO4-induced testicular damage and spermatogenesis disorder. Our study provides a possible targeted therapy for Cu overload-induced reproduction toxicology.

4.
J Mol Cell Biol ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040952

RESUMO

Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB). During vertebrate neural development, RNF220, a ubiquitin E3 ligase, is involved in spinal cord patterning by modulating the subcellular location of glioma-associated oncogene homologs (Glis) through ubiquitination. RNF220 is also required for full activation of Shh signaling during cerebellum development in an epigenetic manner through targeting EED. ZC4H2 was reported to be involved in spinal cord patterning by acting as an RNF220 stabilizer. Here, we provided evidence to show that ZC4H2 is also required for full activation of Shh signaling in CGNP and MB progression by stabilizing RNF220. In addition, we found that the ubiquitin E3 ligase RLIM is responsible for ZC4H2 stabilization via direct ubiquitination, through which RNF220 is also thus stabilized. RLIM is a direct target of Shh signaling and is also required for full activation of Shh signaling in CGNP and MB cell proliferation. We further provided clinical evidence to show that the RLIM‒ZC4H2‒RNF220 cascade is involved in Shh-group MB progression. Disease-causative human RLIM and ZC4H2 mutations affect their interaction and regulation. Therefore, our study sheds light on the regulation of Shh signaling during cerebellar development and MB progression and provides insights into neural disorders caused by RLIM or ZC4H2 mutations.

5.
Zhongguo Zhen Jiu ; 42(1): 51-7, 2022 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-35025158

RESUMO

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION: It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.


Assuntos
Terapia por Acupuntura , Moxibustão , Osteoartrite do Joelho , Pontos de Acupuntura , Humanos , Osteoartrite do Joelho/terapia , Resultado do Tratamento
6.
Trials ; 23(1): 53, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042552

RESUMO

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common chronic neurological complication. It is the main cause of disability in diabetes mellitus (DM) patients and seriously affects the quality of life of patients. Pharmacological treatments always associate with limited efficacy and adverse effects. Moxibustion has been recommended to treat DPN as an adjuvant therapy to conventional medical treatment to accelerate alleviation of the symptoms of DPN. 10.6-µm laser moxibustion (LM), whose wavelength is close to the peak of infrared radiation spectrum of the traditional moxibustion as well as human acupoints, produces the thermal effect similar with moxibustion but with no smoke or smell. The purpose of this sham controlled clinical trial is to determine the effect and safety of 10.6-µm LM as adjuvant therapy in patients with DPN. METHODS: This is a protocol for a randomized, double-blind, sham-controlled trial. One hundred fourteen patients meeting the inclusion and exclusion criteria will be recruited and randomly assigned to the LM group or the sham LM group with a 1:1 allocation ratio. Patients in both groups will receive a basic integrated treatment of Chinese and Western medicine and a total of 12 sessions of true or sham LM treatments over 4 weeks with 3 sessions a week. The primary outcome is nerve conduction velocity (NCV), and the secondary outcomes include Michigan Neuropathy Screening Instrument (MNSI) scores, Diabetes-Specific Quality of Life (DSQL) scores, blood rheology parameters, and assessments of safety and blinding. Outcome measures will be collected at baseline, 2 weeks after treatment, the end of LM treatments (4 weeks), and 4, 8 weeks after the end of LM treatment (8, 12weeks). DISCUSSION: This study will be conducted to compare the efficacy of LM versus sham LM combined with medical treatment. 10.6-µm LM may alleviate symptoms, improve quality of life, and reduce the dosage of drugs as well as avoid causing serious side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029329 . Registered on 25 January 2020.

7.
Lab Invest ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013531

RESUMO

Exosomes, one of three main types of extracellular vesicles, are ~30-100 nm in diameter and have a lipid bilayer membrane. They are widely distributed in almost all body fluids. Exosomes have the potential to regulate unknown cellular and molecular mechanisms in intercellular communication, organ homeostasis, and diseases. They are critical signal carriers that transfer nucleic acids, proteins, lipids, and other substances into recipient cells, participating in cellular signal transduction and material exchange. ncRNAs are non-protein-coding genes that account for over 90% of the genome and include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). ncRNAs are crucial for physiological and pathological activities in the liver by participating in gene transcription, posttranscriptional epigenetic regulation, and cellular processes through interacting with DNA, RNA, or proteins. Recent evidence from both clinical and preclinical studies indicates that exosome-derived noncoding RNAs (ncRNAs) are highly involved in the progression of acute and chronic liver diseases by regulating hepatic lipid metabolism, innate immunity, viral infection, fibrosis, and cancer. Therefore, exosome-derived ncRNAs have promising potential and clinical implications for the early diagnosis, targeted therapy, and prognosis of liver diseases.

8.
Environ Pollut ; 297: 118800, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007671

RESUMO

The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) constitute a major global health problem. The environment plays an important role in the dissemination of CRE, but large-scale studies on CRE in groundwater environments in animal breeding areas are scarce. The aim of this study was to investigate CRE occurrence and environmental transmission of carbapenem resistance genes in large animal breeding areas in northern China. In total, 280 well water and 102 animal feces samples in large animal breeding areas in six counties from the two provinces Inner Mongolia and Shandong in China, were screened for CRE. A total of 39 CRE were isolated and characterized with next-generation sequencing. 5.3% of well water samples were contaminated with CRE. The well water in chicken farms had the highest number of detections of CRE (15.9%). More than half of the isolates carried closely related, conjugative IncX3 plasmids with blaNDM-genes from multiple geographic areas, indicating that this kind of plasmid plays an important role in dissemination of carbapenem resistance determinants. The clonal expansion of various CRE isolates in well water and animal feces were demonstrated; clonally related CRE were isolated from different wells within the same county, from different counties in the same province, and even from different provinces. In addition to harboring various ARGs, two closely related K. pneumoniae belonging to ST11 isolated from well water carried genetic hypervirulence determinants on a virulence plasmid, highlighting the potential health risk posed by further dissemination of this strain. These findings suggest that groundwater may be an underappreciated reservoir and source of dissemination of CRE, from which resistance genes may disseminate among different bacterial strains and over large geographic distances. Further research and multi-sectorial monitoring, with a "One health" perspective, is urgently needed to investigate the need for interventions aimed at preventing CRE dissemination.

9.
PLoS One ; 17(1): e0254265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34990448

RESUMO

Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.

10.
BMC Microbiol ; 22(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979908

RESUMO

BACKGROUND: The resources of wild ginseng have been reducing sharply, and it is mainly dependent on artificial cultivation in China, Korea and Japan. Based on cultivation modes, cultivated ginseng include understory wild ginseng (the seeds or seedlings of cultivated ginseng were planted under the theropencedrymion without human intervention) and farmland cultivated ginseng (grown in farmland with human intervention). Cultivated ginseng, can only be planted on the same plot of land consecutively for several years owing to soilborne diseases, which is mainly because of the variation in the soil microbial community. In contrast, wild ginseng can grow for hundreds of years. However, the knowledge of rhizosphere microbe communities of the wild ginseng is limited. RESULT: In the present study, the microbial communities in rhizosphere soils of the three types of ginseng were analyzed by high-throughput sequencing of 16 S rRNA for bacteria and internal transcribed spacer (ITS) region for fungi. In total, 4,381 bacterial operational taxonomic units (OTUs) and 2,679 fungal OTUs were identified in rhizosphere soils of the three types of ginseng. Among them, the shared bacterial OTUs was more than fungal OTUs by the three types of ginseng, revealing fungal communities were to be more affected than bacterial communities. In addition, the composition of rhizosphere microbial communities and bacterial diversity were similar between understory wild ginseng and wild ginseng. However, higher bacterial diversity and lower fungal diversity were found in rhizosphere soils of wild ginseng compared with farmland cultivated ginseng. Furthermore, the relative abundance of Chloroflexi, Fusarium and Alternaria were higher in farmland cultivated ginseng compared to wild ginseng and understory wild ginseng. CONCLUSIONS: Our results showed that composition and diversity of rhizosphere microbial communities were significantly different in three types of ginseng. This study extended the knowledge pedigree of the microbial diversity populating rhizospheres, and provided insights into resolving the limiting bottleneck on the sustainable development of P. ginseng crops, and even the other crops of Panax.

11.
Ecotoxicol Environ Saf ; 229: 113039, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34922170

RESUMO

Nano-copper has been increasingly employed in various products. In previous studies, we showed that nano-copper caused damage in the rat testis, but it remains unclear whether the toxic reaction can affect the reproductive function. In this study, following 28 d of exposure to nano-copper at a dose of 44, 88, and 175 mg/kg/day, there was a decrease in sperm quality, fructose content, and the secretion of sex hormones. Nano-copper also increased the level of oxidative stress, sperm malformation rate, and induced abnormal structural changes in testicular tissue. Moreover, Nano-copper upregulated the expression of apoptosis-related protein Bax and autophagy-related protein Beclin, and downregulated the expression of Bcl2 and p62. Furthermore, nano-copper (175 mg/kg) downregulated the protein expression of AMPK, p-AKT, mTOR, p-mTOR, p-4E-BP1, p70S6K, and p-p70S6K, and upregulated the protein expression of p-AMPK. Therefore, nano-copper induced damage in testicular tissues and spermatogenesis is highly related to cell apoptosis and autophagy by regulating the Akt/mTOR signaling pathway. In summary, excess exposure to nano-copper may induce testicular apoptosis and autophagy through AKT/mTOR signaling pathways, and damage the reproductive system in adult males, which is associated with oxidative stress in the testes.


Assuntos
Cobre , Testículo , Animais , Apoptose , Autofagia , Cobre/toxicidade , Masculino , Ratos , Transdução de Sinais
12.
J Hazard Mater ; 421: 126815, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34396966

RESUMO

Di (2-ethyl-hexyl) phthalate (DEHP) is a widely used plasticizer. Maternal DEHP exposure inhibits cell proliferation and reduces placentas size, which associates with fetal growth restriction and adulthood diseases. However, the mechanism of placental cell proliferation inhibition by DEHP remains elusive. This study investigated the effect of DEHP on placental cell proliferation from cell cycle arrest. Utilizing in vitro and in vivo experiments, we investigated cell cycle arrest, DNA double-strand break (DSB) repair, genotoxic stress response, and micronuclei formation. Most DEHP metabolizes to mono (2-Ethylhexyl) phthalate (MEHP) and distributes to organs quickly, so MEHP and DEHP were used in cultured cell and animal experiments, respectively. Here, a double blocking mode for the proliferation inhibition of the placental cell was revealed. One is that the classical DSB repair pathways were suppressed, which arrested the cell cycle at the G2/M phase. The other is that DEHP stimulated an elevated level of progesterone, which blocked the cell cycle at metaphase by disrupting chromosome arrangement. These two sets of events facilitated micronuclei formation and resulted in cell proliferation inhibition. This findings provide a novel mechanistic understanding for DEHP to inhibit placental cell proliferation.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/toxicidade , Feminino , Placenta , Plastificantes/toxicidade , Gravidez , Progesterona
13.
Environ Sci Technol ; 56(2): 1138-1148, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34964610

RESUMO

Soil ecotoxicological assays on nanoparticles (NPs) have mainly investigated single components (e.g., plants, fauna, and microbes) within the ecosystem, neglecting possible effects resulting from the disturbance of the interactions between these components. Here, we investigated soil microbial responses to CeO2 NPs in the presence and absence of earthworms from the perspectives of microbial functions (i.e., enzyme activities), the community structure, and soil metabolite profiles. Exposure to CeO2 NPs (50, 500 mg/kg) alone decreased the activities of enzymes (i.e., acid protease and acid phosphatase) participating in soil N and P cycles, while the presence of earthworms ameliorated these inhibitory effects. After the CeO2 NP exposure, the earthworms significantly altered the relative abundance of some microbes associated with the soil N and P cycles (Flavobacterium, Pedobacter, Streptomyces, Bacillus, Bacteroidota, Actinobacteria, and Firmicutes). This was consistent with the pattern found in the significantly changed metabolites which were also involved in the microbial N and P metabolism. Both CeO2 NPs and earthworms changed the soil bacterial community and soil metabolite profiles. Larger alterations of soil bacteria and metabolites were found under CeO2 NP exposure with earthworms. Overall, our study indicates that the top-down control of earthworms can drastically modify the microbial responses to CeO2 NPs from all studied biological aspects. This clearly shows the importance of the holistic consideration of all soil ecological components to assess the environmental risks of NPs to soil health.

14.
Neurochem Int ; 153: 105260, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953963

RESUMO

Vitamin D deficiency and iron accumulation are prevalent in the brains of Alzheimer's disease (AD) patients, however, whether Vitamin D has a role in the regulations of iron metabolism in the condition of AD remains unknown. Our previous studies revealed that vitamin D deficiency promotes ß-amyloid (Aß) deposition in the APP/PS1 mouse brains, while supplemented with a specific agonist of vitamin D receptor (VDR), paricalcitol (PAL), significantly reduced Aß production via promoting the lysosomal degradation of ß-site APP cleavage enzyme 1 (BACE1). In this study, our data suggested that activation of VDR by PAL significantly reduced the iron accumulation in the cortex and hippocampus of APP/PS1 mice through downregulation of Transferrin receptor (TFR) by reducing iron-regulatory protein 2 (IRP2) expression. Furthermore, activation of VDR effectively reduced the phosphorylations of Tau at Ser396 and Thr181 sites via inhibiting the GSK3ß phosphorylation (Tyr216). Taken together, our data suggest that activation of VDR could inhibit the phosphorylations of Tau possibly by repressing the iron accumulation-induced upregulation of GSK3ß activity in the brains of APP/PS1 mice. Thus, activation of VDR may be an effective strategy for treating AD.

15.
J Hazard Mater ; 426: 128123, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968846

RESUMO

Zero-valent iron-embedded biochar (ZVI/BC) is considered as an effective material for arsenic (As) immobilization in soil, but the stability of As after remediation against aging remains unknown. Herein, the effects of dry-wet and freeze-thaw aging on the immobilization of As in two As-contaminated soils amended by ZVI/BC were evaluated. ZVI/BC showed high immobilization capacity for As-contaminated soils with an over 82% decrease of bioavailable As, mainly due to the As-Fe co-precipitation accompanied with ZVI oxidation. The aging of dry-wet and freeze-thaw had an opposite effect on the bioavailability of As. After 35 rounds of dry-wet aging, bioavailable As concentration increased from 1.25-9.50 to 1.83-21.75 mg/kg, because of the oxidation dissolution of ZVI and the formation of mobile reduced As(III). By contrast, the crystallization of amorphous iron with the structural incorporation of sorbed As and the oxidation of As(III) into stable As(V) occurred during the 35 rounds of freeze-thaw aging, leading to the decrease of bioavailable As concentration from 9.50-1.25 to 5.42-0.45 mg/kg. Our results revealed that the stability of soil As after remediation by ZVI/BC varied with the different aging process, which needs more consideration for the long-term soil As immobilization in the different whether areas.

16.
J Hazard Mater ; 424(Pt A): 127268, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34583167

RESUMO

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.


Assuntos
Retardo do Crescimento Fetal , Placenta , Animais , Apoptose , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Gravidez , Ubiquitina-Proteína Ligases/genética
17.
Front Neurol ; 12: 747745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867732

RESUMO

Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures. Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures. Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software. Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB. Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy. Systematic Review Registration: PROSPERO, identifier: CRD42021279029.

18.
Front Endocrinol (Lausanne) ; 12: 741289, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867784

RESUMO

Purpose: Development and validation of a nomogram for the prediction of lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC). Methods: We retrospectively reviewed the clinical features of patients with MTC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 and in our Department of Surgical Oncology, Hangzhou First People's Hospital between 2009 and 2019. The log-rank test was used to compare the difference in the Kaplan-Meier (K-M) curves in recurrence and survival. The nomogram was developed to predict the risk of LLNM in MTC patients. The prediction efficiency of the predictive model was assessed by area under the curve (AUC) and concordance index (C-index) and calibration curves. Decision curve analysis (DCA) was performed to determine the clinic value of the predictive model. Result: A total of 714 patients in the SEER database and 35 patients in our department were enrolled in our study. Patients with LLNM had worse recurrence rate and cancer-specific survival (CSS) compared with patients without LLNM. Five clinical characteristics including sex, tumor size, multifocality, extrathyroidal extension, and distant metastasis were identified to be associated with LLNM in MTC patients, which were used to develop a nomogram. Our prediction model had satisfied discrimination with a C-index of 0.825, supported by both training set and internal testing set with a C-index of 0.825, and 0.816, respectively. DCA was further made to evaluate the clinical utility of this nomogram for predicting LLNM. Conclusions: Male sex, tumor size >38mm, multifocality, extrathyroidal extension, and distant metastasis in MTC patients were significant risk factors for predicting LLNM.

19.
J Virol ; : JVI0194221, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878915

RESUMO

Rabies, caused by rabies virus (RABV), is a widespread zoonosis that is nearly 100% fatal. Alteration of the metabolic environment affects viral replication and the immune response during viral infection. In this study, glucose uptake was increased in mouse brains at the late stage of infection with different RABV strains (lab-attenuated CVS strain and wild-type DRV strain). To illustrate the mechanism underlying glucose metabolism alteration, comprehensive analysis of lysine acetylation and target analysis of energy metabolites in mouse brains infected with CVS and DRV strains were performed. A total of 156 acetylated sites and 115 acetylated proteins were identified as significantly different during RABV infection. Compared to CVS- and mock-infected mice, the lysine acetylation levels of glycolysis and tricarboxylic acid (TCA) cycle enzymes were decreased, and enzyme activity was upregulated in DRV-infected mouse brains. Metabolomic analysis revealed that high levels of oxaloacetate (OAA) in RABV-infected mouse brains. Specifically, the OAA level in CVS-infected mouse brains was higher than that in DRV-infected mouse brains, which contributed to the enhancement of the metabolic rate at the substrate level. Finally, we confirmed that OAA could reduce excessive neuroinflammation in CVS-infected mouse brains by inhibiting JNK and P38 phosphorylation. Taken together, this study provides fresh insight into the different strategies the host adapts to regulate glucose metabolism for energy requirements after different RABV strain infection and suggest that OAA treatment could be a potential strategy to prevent neural damage during RABV infection. IMPORTANCE Both viral replication and the host immune response are highly energy-dependent. It is important to understand how the rabies virus affects energy metabolism in the brain. Glucose is the direct energy source for cell metabolism. Previous studies have revealed that there is some association between acetylation and metabolic processes. In this study, comprehensive protein acetylation and glucose metabolism analysis were conducted to compare glucose metabolism in mouse brains infected with different RABV strains. Our study demonstrates that the regulation of enzyme activity by acetylation and OAA accumulation at the substrate level are two strategies for the host to respond to the energy requirements after RABV infection. Our study also indicates the potential role OAA could play in neuronal protection by suppressing excessive neuroinflammation.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34855352

RESUMO

The sodium super ion conductor (NASICON) structure materials are essential for sodium-ion batteries (SIBs) due to their robust crystal structure, excellent ionic conductivity, and flexibility to regulate element and valence. However, the poor electronic conductivity and inferior energy density caused by the nature of these materials have always been obstacles to commercialization. Herein, using yeast as a template to derive NASICON structure Na3MnTi(PO4)3 (NMTP) materials (noted as Yeast@NMTP/C) is presented. The Yeast@NMTP/C material retains the microsphere morphology of the yeast template and not only controls the particle size (around 2 µm) to shorten the Na+ diffusion pathways but also improves the electronic conductivity to optimize the electrochemical kinetics. The Yeast@NMTP/C cathode delivers reversible multielectron redox reactions including Ti4+/3+, Mn3+/2+, and Mn4+/3+ and exhibits a high capacity of 108.5 mAh g-1 with a 79.2% capacity retention after 1000 cycles at a 2C rate. The sodium storage mechanism of Yeast@NMTP/C reveals that the addition of Ti4+/3+ redox plays a key role in improving the Na+ diffusion kinetics, and both solid-solution and two-phase reactions take place during the desodiation and sodiation process. Additionally, the high-rate and long-span cycle performance of Yeast@NMTP/C at 10C is ascribed to contribute to pseudocapacitance.

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