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The cleavage of inert C-H bonds in methane at room temperature and the subsequent conversion into value-added products are quite challenging. Herein, the reactivity of boron-doped cobalt oxide cluster cations CoBO2+ toward methane under thermal collision conditions was studied by mass spectrometry experiments and quantum-chemical calculations. In this reaction, one H atom and the CH3 unit of methane were transformed separately to generate the product metaboric acid (HBO2) and one CoCH3+ ion, respectively. Theoretical calculations strongly suggest that a catalytic cycle can be completed by the recovery of CoBO2+ through the reaction of CoCH3+ with sodium perborate (NaBO3), and this reaction generates sodium methoxide (CH3ONa) as the other value-added product. This study shows that boron-doped cobalt oxide species are highly reactive to facilitate thermal methane transformation and may open a way to develop more effective approaches for methane (CH4) activation and conversion under mild conditions.
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Compared with transition metals, nonmetallic elements have always been considered to have low reactivity toward carbon dioxide. However, in recent years, main-group compounds such as boron-based species have gradually attracted increasing attention due to their prospective applications in different kinds of reactions. Herein, we report that metal-free anions B2O2- can promote two CO2 reductions, producing the oxygen-rich product B2O4-. In most of the reported CO2 reduction reactions mediated by transition-metal-containing clusters, transition metals usually provide electrons for the activation of CO2; one oxygen atom in CO2 is transferred to metal atoms, and CO is released from the metal atoms. In sharp contrast, B atoms are electron donors in the current systems and the formed CO is liberated directly from the activated CO2 unit. The synthesis of novel-metal-free gas-phase clusters and investigation of their reactivity toward carbon dioxide as well as reaction mechanisms can provide a fundamental basis in practice for the rational design of active sites on metal-free catalysts.
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Transition-metal catalyzed coupling to form C-N bonds is significant in chemical science. However, the inert nature of N2 and CO2 renders their coupling quite challenging. Herein, we report the activation of dinitrogen in the mild plasma atmosphere by the gas-phase monometallic YB1-4 - anions and further coupling of CO2 to form C-N bonds by using mass spectrometry and theoretical calculation. The observed product anions are NCNBO- and N(BO)2 - , accompanied by the formation of neutral products YO and YB0-2 NC, respectively. We can tune the reactivity and the type of products by manipulating the number of B atoms. The B atoms in YB1-4 N2 - act as electron donors in CO2 reduction reactions, and the carbon atom originating from CO2 serves as an electron reservoir. This is the first example of gas-phase monometallic anions, which are capable to realize the functionalization of N2 with CO2 through C-N bond formation and N-N and C-O bond cleavage.
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Alkali atoms are usually used as promoters to significantly increase the catalytic activity of transition-metal catalysts in a wide range of reactions such as dinitrogen conversion reactions. However, the role of alkali metal atoms remains controversial. Herein, a series of quaternary cluster anions containing lithium atoms Nb2LiNO1-4- have been synthesized and reacted with N2 at room temperature. The detailed experimental and theoretical investigations indicate that Nb2LiNO- is capable to cleave the N≡N bond and the Li atoms in Nb2LiNO1,2- act as electron donors in the N2 reduction reaction. With the increase in the number of oxygen atoms, the reactivity toward N2 is reduced from adsorption via a side-on end-on mode in Nb2LiNO2- to the inertness of Nb2LiNO4-. In Nb2LiNO3,4- anions, the Li atoms are bonded with oxygen atoms, acting as structural units to stabilize structures. Therefore, the roles of alkali atoms are able to change with different chemical environments of active sites. For the first time, we reveal how the number of ligands (oxygen atoms herein) can be used to finely regulate the reactivity toward N2.
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Studies have shown silver nanoparticles (AgNPs) exposure can result in a series of toxic effects in fish gills. However, it is still unclear how AgNPs affect metabolite expression and their related molecular metabolic pathways in fish gills. In this study, we employed untargeted metabolomics to study the effects of AgNPs and silver supernatant ions on fish gill metabolites. The results showed that AgNPs can induce significant changes in 96 differentially expressed metabolites, which mainly affect amino acid metabolism and energy metabolism in fish gills. Among these metabolites, AgNPs specifically induce significant changes in 72 differentially expressed metabolites, including L-histidine, L-isoleucine, L-phenylalanine, and citric acid. These metabolites were significantly enriched in the pathways of aminoacyl-tRNA biosynthesis, ABC transporters, and the citrate cycle. In contrast, Ag+ supernatant exposure can specifically induce significant changes in 14 differentially expressed metabolites that mainly interfere with sphingolipid metabolism in fish gills. These specifically regulated fish gill metabolites include sphinganine, sphingosine, and phytosphingosine, which were significantly enriched in the sphingolipid metabolism pathway. Our results clearly reveal the effects and potential toxicity mechanisms of AgNPs on fish gill metabolites. Furthermore, our study further determined the unique functions of released silver ions in AgNPs toxicity in fish gills.
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Carpas , Nanopartículas del Metal , Animales , Branquias , Metabolómica , Nanopartículas del Metal/toxicidad , Plata/toxicidadRESUMEN
BACKGROUND: Intra-body communication (IBC) is one of the highlights in studies of body area networks. The existing IBC studies mainly focus on human channel characteristics of the physical layer, transceiver design for the application, and the protocol design for the networks. However, there are few safety analysis studies of the IBC electrical signals, especially for the galvanic-coupled type. Besides, the human channel model used in most of the studies is just a multi-layer homocentric cylinder model, which cannot accurately approximate the real human tissue layer. METHODS: In this paper, the empirical arm models were established based on the geometrical information of six subjects. The thickness of each tissue layer and the anisotropy of muscle were also taken into account. Considering the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines, the restrictions taken as the evaluation criteria were the electric field intensity lower than 1.35 × 104 f V/m and the specific absorption rate (SAR) lower than 4 W/kg. The physiological electrode LT-1 was adopted in experiments whose size was 4 × 4 cm and the distance between each center of adjoining electrodes was 6 cm. The electric field intensity and localized SAR were all computed by the finite element method (FEM). The electric field intensity was set as average value of all tissues, while SAR was averaged over 10 g contiguous tissue. The computed data were compared with the 2010 ICNIRP guidelines restrictions in order to address the exposure restrictions of galvanic-coupled IBC electrical signals injected into the body with different amplitudes and frequencies. RESULTS: The input alternating signal was 1 mA current or 1 V voltage with the frequency range from 10 kHz to 1 MHz. When the subject was stimulated by a 1 mA alternating current, the average electric field intensity of all subjects exceeded restrictions when the frequency was lower than 20 kHz. The maximum difference among six subjects was 1.06 V/m at 10 kHz, and the minimum difference was 0.025 V/m at 400 kHz. While the excitation signal was a 1 V alternating voltage, the electric field intensity fell within the exposure restrictions gradually as the frequency increased beyond 50 kHz. The maximum difference among the six subjects was 2.55 V/m at 20 kHz, and the minimum difference was 0.54 V/m at 1 MHz. In addition, differences between the maximum and the minimum values at each frequency also decreased gradually with the frequency increased in both situations of alternating current and voltage. When SAR was introduced as the criteria, none of the subjects exceeded the restrictions with current injected. However, subjects 2, 4, and 6 did not satisfy the restrictions with voltage applied when the signal amplitude was ≥ 3, 6, and 10 V, respectively. The SAR differences for subjects with different frequencies were 0.062-1.3 W/kg of current input, and 0.648-6.096 W/kg of voltage input. CONCLUSION: Based on the empirical arm models established in this paper, we came to conclusion that the frequency of 100-300 kHz which belong to LF (30-300 kHz) according to the ICNIRP guidelines can be considered as the frequency restrictions of the galvanic-coupled IBC signal. This provided more choices for both intensities of current and voltage signals as well. On the other hand, it also makes great convenience for the design of transceiver hardware and artificial intelligence application. With the frequency restrictions settled, the intensity restrictions that the current signal of 1-10 mA and the voltage signal of 1-2 V were accessible. Particularly, in practical application we recommended the use of the current signals for its broad application and lower impact on the human tissue. In addition, it is noteworthy that the coupling structure design of the electrode interface should attract attention.
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Electricidad , Análisis de Elementos FinitosRESUMEN
OBJECTIVE: To study the clinical application of ultrasonic cardiac output monitor (USCOM) in evaluation of cardiac function in children with severe pneumonia. METHODS: Twenty-nine children with severe pneumonia were enrolled in the observation group and forty-three children with common pneumonia were enrolled in the control group. The USCOM was used to measure the cardiac function indices in the two groups. The results were compared between the two groups. The changes in cardiac function indices after treatment were evaluated in the observation group. ESULTS: The observation group had a significantly higher heart rate and significantly lower cardiac output, systolic volume, and aortic peak velocity than the control group (P<0.05). There were no significant differences in cardiac index or systemic vascular resistance between the two groups (P>0.05). In the observation group, the heart rate, cardiac output, systolic volume, aortic peak velocity, cardiac index, and systemic vascular resistance were significantly improved after treatment (P<0.05). CONCLUSIONS: The USCOM is a fast, convenient, and accurate approach for dynamic measurement of cardiac function and overall circulation state in children with severe pneumonia. The USCOM can provide a basis for diagnosis, treatment, and evaluation of the disease, which is quite useful in clinical practice.
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Gasto Cardíaco/fisiología , Monitoreo Fisiológico/instrumentación , Neumonía/fisiopatología , Ultrasonido , Niño , Femenino , Humanos , Lactante , MasculinoRESUMEN
Current efforts in nonviral gene therapy are plagued by a pervasive difficulty in sustaining therapeutic levels of delivered transgenes. Minicircles (plasmid derivatives with the same expression cassette but lacking a bacterial backbone) show sustained expression and hold promise for therapeutic use where persistent transgene expression is required. To characterize the widely-observed silencing process affecting expression of foreign DNA in mammals, we used a system in which mouse liver presented with either plasmid or minicircle consistently silences plasmid but not minicircle expression. We found that preferential silencing of plasmid DNA occurs at a nuclear stage that precedes transport of mRNA to the cytoplasm, evident from a consistent >25-fold minicircle/plasmid transcript difference observed in both nuclear and total RNA. Among possible mechanisms of nuclear silencing, our data favor chromatin-linked transcriptional blockage rather than targeted degradation, aberrant processing, or compromised mRNA transport. In particular, we observe dramatic enrichment of H3K27 trimethylation on plasmid sequences. Also, it appears that Pol II can engage the modified plasmid chromatin, potentially in a manner that is not productive in the synthesis of high levels of new transcript. We outline a scenario in which sustained differences at the chromatin level cooperate to determine the activity of foreign DNA.
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Cromatina/metabolismo , ADN Circular/genética , Vectores Genéticos , Transcripción Genética , Animales , Inmunoprecipitación de Cromatina , Metilación de ADN , Histonas/metabolismo , Hígado/metabolismo , RatonesRESUMEN
Clinical trials reveal that plasmid DNA (pDNA)-based gene delivery must be improved to realize its potential to treat human disease. Current pDNA platforms suffer from brief transgene expression, primarily due to the spread of transcriptionally repressive chromatin initially deposited on plasmid bacterial backbone sequences. Minicircle (MC) DNA lacks plasmid backbone sequences and correspondingly confers higher levels of sustained transgene expression upon delivery, accounting for its success in preclinical gene therapy models. In this study, we show for the first time that MC DNA also functions as a vaccine platform. We used a luciferase reporter transgene to demonstrate that intradermal delivery of MC DNA, relative to pDNA, resulted in significantly higher and persistent levels of luciferase expression in mouse skin. Next, we immunized mice intradermally with DNA encoding a peptide that, when presented by the appropriate major histocompatibility complex class I molecule, was recognized by endogenous CD8(+) T cells. Finally, immunization with peptide-encoding MC DNA, but not the corresponding full-length (FL) pDNA, conferred significant protection in mice challenged with Listeria monocytogenes expressing the model peptide. Together, our results suggest intradermal delivery of MC DNA may prove more efficacious for prophylaxis than traditional pDNA vaccines.
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Linfocitos T CD8-positivos/inmunología , ADN Circular/inmunología , Epítopos de Linfocito T/inmunología , Plásmidos/inmunología , Traslado Adoptivo , Animales , Presentación de Antígeno/inmunología , Línea Celular , ADN Circular/genética , Epítopos de Linfocito T/genética , Femenino , Expresión Génica , Orden Génico , Genes Reporteros , Vectores Genéticos/genética , Humanos , Listeriosis/inmunología , Listeriosis/prevención & control , Ratones , Plásmidos/genética , Piel/metabolismo , Transgenes/inmunología , Vacunas de ADN/genética , Vacunas de ADN/inmunologíaRESUMEN
BACKGROUND: The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head, maintaining shoulder joint stability. AIM: To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries. METHODS: We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023. Patients were grouped using the envelope method. RESULTS: After treatment, the study group's treatment effective rate was 94.90% (46/49 patients), significantly higher than that in the control group (79.17%, 38/48 cases; P < 0.05). Before treatment, there was no difference in Constant Murley Score (CMS) scores, shoulder mobility, or 36-Item Short Form Health Survey (SF-36) scale scores (P > 0.05). Compared with those before treatment, the CMS scores (including pain, daily living ability, shoulder mobility, and muscle strength), all aspects of shoulder mobility (forward flexion, posterior extension, external rotation, internal rotation), and SF-36 scale scores (including physiological, psychological, emotional, physical, vitality, and health status) were higher in both groups after treatment and significantly higher in the study group (P < 0.05). There was no difference in the occurrence of complications between the two treatment groups (P > 0.05). CONCLUSION: Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries, helps accelerate the recovery of shoulder function, improves the quality of life, and is highly safe.
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BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.
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Owing to the risk of insertional mutagenesis, viral transduction has been increasingly replaced by nonviral methods to generate induced pluripotent stem cells (iPSCs). We report the use of 'minicircle' DNA, a vector type that is free of bacterial DNA and capable of high expression in cells, for this purpose. Here we use a single minicircle vector to generate transgene-free iPSCs from adult human adipose stem cells.
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ADN Circular/genética , Vectores Genéticos , Células Madre Pluripotentes Inducidas/metabolismo , Adulto , Humanos , TransfecciónRESUMEN
Dinitrogen (N2) activation and its chemical transformations are some of the most challenging topics in chemistry. Herein, we report that heteronuclear metal anions AuNbBO- can mediate the direct coupling of N2 and O2 to generate NO molecules. N2 first forms the nondissociative adsorption product AuNbBON2- on AuNbBO-. In the following reactions with two O2 molecules, two NO molecules are gradually released, with the formation of AuNbBO2N- and AuNbBO3-. In the reaction with the first O2, the generated nitrene radical (Nâ¢â¢-) originating from the dissociated N2, induces the activation of O2. Subsequently, the second O2 is anchored and forms a superoxide radical (O2â¢-); this radical attacks the other N atom to form an N-O bond, releasing the second NO. The Nâ¢â¢- and O2â¢- radicals play key roles in the reactions. The mechanism adopted in this direct oxidation of N2 by O2 to NO can be labeled as a Zeldovich-like mechanism.
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Paracanthocobitis putaoensis sp. nov. is described based on analysis of morphological and molecular data (cytochrome c oxidase subunit I-COI). The new species was collected from the Mali Hka River, a tributary of the Irrawaddy River near Putao in Kachin State in northern Myanmar. It can be easily distinguished from all other species of the genus Paracanthocobitis by an incomplete lateral line, a suborbital groove in adult males, and a well-developed axillary pelvic lobe. Phylogenetic relationships of the genus Paracanthocobitis based on the mitochondrial COI locus are revealed for the first time. Maximum likelihood and Bayesian inference phylogenetic analyses indicate that the new species forms an independent clade. Both morphological and molecular phylogenetic analyses suggest that P. putaoensis is a new species.
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Cipriniformes , Masculino , Animales , Filogenia , Teorema de Bayes , Mianmar , RíosRESUMEN
Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites. Bispecific T-cell engagers (BiTEs) have demonstrated impressive antitumor efficacy in hematological malignancies, but the clinical potency is limited by their short half-life, inconvenient continuous intravenous infusion, and severe toxicity at relevant therapeutic levels in solid tumors. To address these critical issues, the design and engineering of alendronate calcium (CaALN) based gene-delivery system is reported to express therapeutic level of BiTE (HER2×CD3) for efficient ovarian cancer immunotherapy. Controllable construction of CaALN nanosphere and nanoneedle is achieved by the simple and green coordination reactions that the distinct nanoneedle-like alendronate calcium (CaALN-N) with a high aspect ratio enabled efficient gene delivery to the peritoneum without system in vivo toxicity. Especially, CaALN-N induced apoptosis of SKOV3-luc cell via down-regulation of HER2 signaling pathway and synergized with HER2×CD3 to generate high antitumor response. In vivo administration of CaALN-N/minicircle DNA encoding HER2×CD3 (MC-HER2×CD3) produces sustained therapeutic levels of BiTE and suppresses tumor growth in a human ovarian cancer xenograft model. Collectively, the engineered alendronate calcium nanoneedle represents a bifunctional gene delivery platform for the efficient and synergistic treatment of ovarian cancer.
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Calcio , Neoplasias Ováricas , Femenino , Humanos , Alendronato/metabolismo , Alendronato/uso terapéutico , Calcio/metabolismo , Línea Celular Tumoral , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Linfocitos T/metabolismo , AnimalesRESUMEN
Intracerebral hemorrhage (ICH), which has high mortality and disability rate is associated with microglial pyroptosis and neuroinflammation, and the effective treatment methods are limited Epigallocatechin-3-gallate (EGCG) has been found to play a cytoprotective role by regulating the anti-inflammatory response to pyroptosis in other systemic diseases. However, the role of EGCG in microglial pyroptosis and neuroinflammation after ICH remains unclear. In this study, we investigated the effects of EGCG pretreatment on neuroinflammation-mediated neuronal pyroptosis and the underlying neuroprotective mechanisms in experimental ICH. EGCG pretreatment was found to remarkably improved neurobehavioral performance, and decreased the hematoma volume and cerebral edema in mice. We found that EGCG pretreatment attenuated the release of hemin-induced inflammatory cytokines (IL-1ß, IL-18, and TNF-α). EGCG significantly upregulated the expression of heme oxygenase-1 (HO-1), and downregulated the levels of pyroptotic molecules and inflammatory cytokines including Caspase-1, GSDMD, NLRP3, mature IL-1ß, and IL-18. EGCG pretreatment also decreased the number of Caspase-1-positive microglia and GSDMD along with NLRP3-positive microglia after ICH. Conversely, an HO-1-specific inhibitor (ZnPP), significantly inhibited the anti-pyroptosis and anti-neuroinflammation effects of EGCG. Therefore, EGCG pretreatment alleviated microglial pyroptosis and neuroinflammation, at least in part through the Caspase-1/GSDMD/NLRP3 pathway by upregulating HO-1 expression after ICH. In addition, EGCG pretreatment promoted the polarization of microglia from the M1 phenotype to M2 phenotype after ICH. The results suggest that EGCG is a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.
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Hemorragia Cerebral , Hemo-Oxigenasa 1 , Microglía , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores , Animales , Ratones , Caspasas/metabolismo , Caspasas/farmacología , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Citocinas/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/efectos de los fármacos , Piroptosis/genética , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease characterized by mutations to the α-L-iduronidase (IDUA) gene resulting in inactivation of the IDUA enzyme. The loss of IDUA protein results in the progressive accumulation of glycosaminoglycans within the lysosomes resulting in severe, multi-organ system pathology. Gene replacement strategies have relied on the use of viral or nonviral gene delivery systems. Drawbacks to these include laborious production procedures, poor efficacy due to plasmid-borne gene silencing, and the risk of insertional mutagenesis. This report demonstrates the efficacy of a nonintegrating, minicircle (MC) DNA vector that is resistant to epigenetic gene silencing in vivo. To achieve sustained expression of the immunogenic IDUA protein we investigated the use of a tissue-specific promoter in conjunction with microRNA target sequences. The inclusion of microRNA target sequences resulted in a slight improvement in long-term expression compared to their absence. However, immune modulation by costimulatory blockade was required and permitted for IDUA expression in MPS I mice that resulted in the biochemical correction of pathology in all of the organs analyzed. MC gene delivery combined with costimulatory pathway blockade maximizes safety, efficacy, and sustained gene expression and is a new approach in the treatment of lysosomal storage disease.
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ADN Circular/genética , Terapia Genética , Vectores Genéticos , Iduronidasa/genética , Iduronidasa/metabolismo , Inmunomodulación , Mucopolisacaridosis I/terapia , Animales , ADN Circular/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Orden Génico , Vectores Genéticos/genética , Glicosaminoglicanos/metabolismo , Humanos , Inmunidad Activa , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones SCID , MicroARNs/genética , MicroARNs/metabolismo , Mucopolisacaridosis I/enzimología , Mucopolisacaridosis I/inmunología , Plásmidos/genética , Plásmidos/metabolismoRESUMEN
Background: Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced peripheral neurotoxicity (OIPN) has been well documented. Traditional Chinese medicine injections (TCMIs) have shown significant efficacy in preventing OIPN. However, it is difficult for clinicians to determine the differences in the efficacy of various TCMIs in preventing OIPN. The aim of this study was to compare the efficacy of various TCMIs in preventing OIPN through a network meta-analysis (NMA) to further inform clinical decision-making. Methods: The Chinese Journal Full Text Database, Chinese Biomedical Literature Database, Wanfang Data Knowledge Service Platform, Chinese Science and Technology Journal Full Text Database, the Cochrane Library, Web of Science, PubMed, and Embase databases were searched for randomized controlled trials (RCTs) of TCMIs for OIPN prevention. The retrieval time was from the establishment of the database to April 12, 2021. NMA was performed using Stata 14.0 software after 2 evaluators independently screened the literature, extracted information, and evaluated the risk of bias of the included studies. Results: A total of 45 eligible RCTs involving 3598 cancer patients and 13 TCMIs were included. The 13 TCMIs included Xiaoaiping injection (XAPI), compound kushen injection (CKSI), Aidi injection (ADI), Brucea javanica oil emulsion injection (BJOEI), Shenmai injection (SMI), Kangai injection (KAI), Astragalus injection (AI), elemene emulsion injection (EEI), Shenfu injection (SFI), Shenqi Fuzheng injection (SIFZI), Kanglaite injection (KLEI), Huachansu injection (HCSI), and lentinan injection (LI). NMA results showed that AI was superior to AD and SIFZI was superior to ADI in reducing the incidence of grade I neurotoxicity. SIFZI was superior to EEI and ADI, and BJOEI was superior to chemotherapy alone in reducing the incidence of grade II neurotoxicity. SMI was superior to LI and CKSI in reducing the incidence of grade III neurotoxicity. SIFZI was superior to LI, BJOEI, XAPI, EEI, SMI, chemotherapy alone, HCSI, KLEI, and ADI in reducing the total incidence of grade I-IV neurotoxicity. SFI was superior to ADI. Based on the SUCRA values, AI was the most likely intervention to reduce the incidence of grade I neurotoxicity, SIFZI was the most likely intervention to reduce the total incidence of grade II and I-IV neurotoxicity, and SMI was the most likely intervention to reduce the incidence of grade III and IV neurotoxicity. Conclusion: TCMIs can prevent OIPN to some extent, among which SIFZI, SMI, and AI may be the most promising TCMIs. However, given the limitations of current studies, more well-designed, high-quality clinical trials will be needed in the future to validate the benefits of TCMIs.
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The conversion of dinitrogen to more useful and reactive molecules has been the focus of intense research by chemists. In contrast to reductive N2 fixation, direct oxidation of N2 by O2 to nitric oxide under mild conditions via a thermochemical process is extremely challenging. Herein, we report the first example of N2 and O2 activation and coupling under thermochemical conditions through the remarkable ability of Y2BO+ to react with one N2 and two O2 molecules. Detailed mechanistic studies using mass spectrometry and quantum chemical calculations revealed that the N2 activation by Y2BO+ is facilitated by the double aromatic character of the Y2BON2+ intermediate. Subsequent oxidation with O2 releases NO in a dearomatization process driven by the formation of stronger Y-O bonds over the Y-N bonds. Our findings represent the first example of N2 and O2 activation and coupling under thermochemical conditions at room temperature, providing a novel strategy for small-molecule activation.
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Mitochondria are recognized as an important target organelle for the toxicity of nanomaterials. Although the toxic effects of silver nanoparticles (AgNPs) on mitochondria have been widely reported, the mechanism behind the toxicity remains unclear. In this study, the effects of two forms of silver (AgNPs and AgNO3) on carp gill mitochondria were investigated by analyzing the mitochondrial ultrastructure, physicochemical properties of mitochondrial membrane, and mitochondrial proteomics. After exposure of common carp to AgNPs (0.75 mg/L) and AgNO3 (0.05 mg/L) for 96 h, both forms of silver were shown to cause gill mitochondrial lesions, including irregular shape, loss of mitochondrial cristae, and increased mitochondrial membrane permeability. Proteomics results revealed that AgNPs and AgNO3 induced 362 and 297 differentially expressed proteins (DEPs) in gill mitochondria, respectively. Among the DEPs, 244 were shared between AgNPs and AgNO3 treatments. These shared proteins were mainly distributed in the mitochondrial membrane and matrix, and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathway. The functional annotation of DEPs induced by both silver forms was mainly involved in energy production and conversion. These results indicated that the toxic mechanism of AgNPs and AgNO3 on gill mitochondria were comparable and the two forms of silver caused mitochondrial dysfunction in fish gills by inhibiting the TCA cycle and disrupting the electron transport chain.